RESUMO
BACKGROUND: An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival. METHODS: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety. RESULTS: Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events. CONCLUSIONS: Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiorradioterapia , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Infusões Intravenosas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
PURPOSE: There is significant interest in the development of targeted alpha-particle therapies (TATs) for treatment of solid tumors. The metal chelator-peptide conjugate, DOTA-TATE, loaded with the ß-particle emitting radionuclide 177Lu ([177Lu]Lu-DOTA-TATE) is now standard care for neuroendocrine tumors that express the somatostatin receptor 2 (SSTR2) target. A recent clinical study demonstrated efficacy of the corresponding [225Ac]Ac-DOTA-TATE in patients that were refractory to [177Lu]Lu-DOTA-TATE. Herein, we report the radiosynthesis, toxicity, biodistribution (BD), radiation dosimetry (RD), and efficacy of [225Ac]Ac-DOTA-TATE in small animal models of lung neuroendocrine neoplasms (NENs). METHODS: [225Ac]Ac-DOTA-TATE was synthesized and characterized for radiochemical yield, purity and stability. Non-tumor-bearing BALB/c mice were tested for toxicity and BD. Efficacy was determined by single intravenous injection of [225Ac]Ac-DOTA-TATE into SCID mice-bearing human SSTR2 positive H727 and H69 lung NENs. RD was calculated using the BD data. RESULTS: [225Ac]Ac-DOTA-TATE was synthesized with 98% yield, 99.8% purity, and displayed 97% stability after 2 days incubation in human serum at 37 °C. All animals in the toxicity study appeared healthy 5 months post injection with no indications of toxicity, except that animals that received ≥111 kBq of [225Ac]Ac-DOTA-TATE had chronic progressive nephropathy. BD studies revealed that the primary route of elimination is by the renal route. RD calculations determined pharmacokinetics parameters and absorbed α-emission dosages from 225Ac and its daughters. For both tumor models, a significant tumor growth delay and time to experimental endpoint were observed following a single administration of [225Ac]Ac-DOTA-TATE relative to controls. CONCLUSIONS: These results suggest significant potential for the clinical translation of [225Ac]Ac-DOTA-TATE for lung NENs.
Assuntos
Neoplasias Pulmonares , Compostos Organometálicos , Animais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Octreotida/uso terapêutico , Octreotida/toxicidade , Compostos Organometálicos/uso terapêutico , Compostos Organometálicos/toxicidade , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/toxicidade , Distribuição TecidualRESUMO
BACKGROUND: Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. METHODS: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. RESULTS: Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events. CONCLUSIONS: Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Human telomerase reverse transcriptase (hTERT) is an antigen that may represent a target for a novel anti-cancer strategy. A pilot, phase I study tested the safety and feasibility of a prime-boost immunization regimen based on V935, an adenoviral type 6 vector vaccine expressing a modified version of hTERT, administered alone or in combination with V934, a DNA plasmid that also expresses the same antigen and is delivered using the electroporation injection technique. METHODS: Treatments: Group #1 received two doses (low-dose: 0.5 × 109 vg, and high-dose: 0.5 × 1011 vg) of V935 followed by a 4-week observation period. Group #2 received three doses of V934-electroporation and two doses of V935 following a 4-week observation period. Doses were low-dose V934 (0.25 mg of plasmid) with low-dose V935 (0.5 × 109 vg); high-dose V934 (2.5 mg of plasmid) with high-dose V935 (0.5 × 1011 vg). Group #3 received five doses of V934-EP and two doses of V935: V934 was administered IM every 2 weeks for five doses. Following a 4-week observation period, V935 was administered IM every 2 weeks for two doses followed by a 4-week observation period. One (1) dose level was tested in treatment group #3: high-dose V934 (2.5 mg of plasmid), in combination with high-dose V935 (0.5 × 1011 vg). Immunogenicity was measured by ELISPOT assay and three pools of peptides encompassing the sequence of hTERT. RESULTS: In total, 37 patients affected by solid tumors (prostate cancer in 38%) were enrolled. The safety profile of different regimens was good and comparable across groups, with no severe adverse events, dose-limiting toxicities or treatment discontinuations. As expected, the most common adverse events were local reactions. A significant increase in ELISPOT responses against hTERT peptide pool 2 was observed (p < 0.01), while no evidence of boosting was observed for peptide pools 1 and 3. This was also evident for group #1 and #2 separately. In patients with prostate cancer, there was a significant increase in ELISPOT response against hTERT peptide pool 2 following immunization (p < 0.01), regardless of previous therapy, immunosuppressing agents, or adenoviral type 6 titers at screening. CONCLUSION: Our results suggest the safety and feasibility of V934/V935 hTERT vaccination in cancer patients with solid tumors Trial Registration Name of the registry: ClinicalTrial.gov Trial registration number: NCT00753415 Date of registration: 16 September 2008 Retrospectively registered URL of trial registry record: https://clinicaltrials.gov/ct2/results?cond=&term=NCT00753415&cntry=&state=&city=&dist=.
Assuntos
Neoplasias , Vacinas Virais , Adenoviridae/genética , Vetores Genéticos , Humanos , Masculino , Neoplasias/terapia , VacinaçãoRESUMO
BACKGROUND: In the ongoing, phase 3 PACIFIC trial, durvalumab improved the primary endpoints of progression-free survival and overall survival compared with that for placebo, with similar safety, in patients with unresectable, stage III non-small-cell lung cancer. In this analysis, we aimed to evaluate one of the secondary endpoints, patient-reported outcomes (PROs). METHODS: PACIFIC is an ongoing, international, multicentre, double-blind, randomised, controlled, phase 3 trial. Eligible patients were aged at least 18 years, had a WHO performance status of 0 or 1, with histologically or cytologically documented stage III, unresectable non-small-cell lung cancer, for which they had received at least two cycles of platinum-based chemoradiotherapy, with no disease progression after this treatment. We randomly assigned patients (2:1) using an interactive voice response system and a blocked design (block size=3) stratified by age, sex, and smoking history to receive 10 mg/kg intravenous durvalumab or matching placebo 1-42 days after concurrent chemoradiotherapy, then every 2 weeks up to 12 months. The primary endpoints of progression-free survival and overall survival have been reported previously. PROs were a prespecified secondary outcome. We assessed PRO symptoms, functioning, and global health status or quality of life in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) at the time of random allocation to groups, at weeks 4 and 8, every 8 weeks until week 48, and then every 12 weeks until progression. Changes from baseline to 12 month in key symptoms were analysed with mixed model for repeated measures (MMRM) and time-to-event analyses. A 10-point or greater change from baseline (deterioration or improvement) was deemed clinically relevant. This study is registered with ClinicalTrials.gov, NCT02125461, and EudraCT, 2014-000336-42. FINDINGS: Between May 9, 2014, and April 22, 2016, 476 patients were assigned to receive durvalumab, and 237 patients were assigned to receive placebo. As of March 22, 2018, the median follow-up was 25·2 months (IQR 14·1-29·5). More than 79% of patients given durvalumab and more than 82% of patients given placebo completed questionnaires up to week 48. Between baseline and 12 months, the prespecified longitudinal PROs of interest, cough (MMRM-adjusted mean change 1·8 [95% CI 0·06 to 3·54] in the durvalumab group vs 0·7 [-1·91 to 3·30] in the placebo group), dyspnoea (3·1 [1·75 to 4·36] vs 1·4 [-0·51 to 3·34]), chest pain (-3·1 [-4·57 to -1·60] vs -3·5 [-5·68 to -1·29]), fatigue (-3·0 [-4·53 to -1·50] vs -5·2 [-7·45 to -2·98]), appetite loss (-5·8 [-7·28 to -4·36] vs -7·0 [-9·17 to -4·87]), physical functioning (0·1 [-1·10 to 1·28] vs 2·0 [0·22 to 3·73]), and global health status or quality of life (2·6 [1·21 to 3·94] vs 1·8 [-0·25 to 3·81]) remained stable with both treatments, with no clinically relevant changes from baseline. The between-group differences in changes from baseline to 12 months in cough (difference in adjusted mean changes 1·1, 95% CI -1·89 to 4·11), dyspnoea (1·6, -0·58 to 3·87), chest pain (0·4, -2·13 to 2·93), fatigue (2·2, -0·38 to 4·78), appetite loss (1·2, -1·27 to 3·67), physical functioning (-1·9, -3·91 to 0·15), or global health status or quality of life (0·8, -1·55 to 3·14) were not clinically relevant. Generally, there were no clinically important between-group differences in time to deterioration of prespecified key PRO endpoints. INTERPRETATION: Our findings suggest that a clinical benefit with durvalumab can be attained without compromising PROs. This result is of note because the previous standard of care was observation alone, with no presumed detriment to PROs. FUNDING: AstraZeneca.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia/mortalidade , Neoplasias Pulmonares/mortalidade , Medidas de Resultados Relatados pelo Paciente , Adolescente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Bypass activation of Src family kinases can confer resistance to EGFR tyrosine kinase inhibitors (TKIs) based on preclinical models. We prospectively assessed the safety and clinical activity of dasatinib and afatinib in combination for patients with resistant EGFR-mutant lung cancer. METHODS: An open-label, dose-escalation phase 1/2 trial (NCT01999985) with 2-stage expansion was conducted with 25 lung cancer patients. Dose expansion required activating EGFR mutations and progression following prior EGFR TKI. RESULTS: Patients were 72% Caucasian and received median of 2 prior lines of therapy. Maximum-tolerated dose was 30 mg afatinib with 100 mg dasatinib. New or increased pleural effusions were observed in 56% of patients. No radiologic responses were observed, although several EGFR-mutant TKI-resistant patients (26%) had prolonged stable disease over 6 months. The combination reduced the EGFR mutation and T790M variant allele frequency in cell-free DNA (p < .05). Nonetheless, the threshold for futility was met, based on 6-month progression-free survival. For EGFR TKI-resistant patients, median progression-free survival was 3.7 months (95% confidence interval (CI), 2.3-5.0) and overall survival was 14.7 months (95% CI, 8.5-20.9). CONCLUSIONS: The combination had a manageable toxicity profile and in vivo T790M modulation, but no objective clinical responses were observed.
Assuntos
Afatinib/administração & dosagem , Dasatinibe/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Afatinib/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Nucleicos Livres/efeitos dos fármacos , Dasatinibe/efeitos adversos , Progressão da Doença , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Receptores ErbB/genética , Feminino , Frequência do Gene , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Quinases da Família src/antagonistas & inibidoresRESUMO
Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3-48.6) and 43.3% of arm C (95% CI 23.9-65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7-46.3), 16.7% (95% CI 2.9-49.1), and 23.8% (95% CI 9.1-47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.
Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Proteína Supressora de Tumor p53/genética , Vacinação , Adulto , Idoso , Vacinas Anticâncer/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Terapia de Salvação , Carcinoma de Pequenas Células do Pulmão/mortalidade , TransfecçãoRESUMO
OBJECTIVE: Loneliness, or the discrepancy between perceived and desired level of social connectedness, is an understudied but important psychosocial factor in cancer patients. The current study investigated the relationship between loneliness, depressive symptoms, quality of life, and social cognitive variables (eg, stigma, social constraint, and cancer-related negative social expectations), and explored loneliness as a mediator of the relationship between social cognitive variables and depressive symptoms and quality of life in lung cancer patients beginning treatment. METHODS: Patients within 3 months of beginning treatment for lung cancer completed measures of loneliness, depressive symptoms, quality of life, and social cognitive variables. Correlational, chi-square, and hierarchical regression analyses evaluated relationships among variables. Bias-corrected bootstrapping methods estimated the indirect effect and 95% confidence interval for mediation models. RESULTS: Participants (n = 105, M = 65.5 years, 55% female) endorsed low to moderate levels of loneliness. Greater loneliness was associated with greater depressive symptoms and worse quality of life (P's < .001), and loneliness explained unique variance in depressive symptoms (F = 10.18, P < .001, ΔR2 = .06, Total R2 = .35) and quality of life (F = 19.55, P < .001, ΔR2 = .05, Total R2 = .52) after controlling for significant covariates. Greater stigma, social constraint, and cancer-related negative social expectations were associated with greater loneliness and depressive symptoms and worse quality of life (P's < .001). Loneliness partially mediated the relationship of social cognitive variables with depressive symptoms and quality of life. CONCLUSIONS: Beyond its direct impact on clinically relevant outcomes, the experience of loneliness may be a mechanism by which social cognitive factors influence depressive symptoms and quality of life in lung cancer patients.
Assuntos
Depressão/psicologia , Solidão/psicologia , Neoplasias Pulmonares/psicologia , Qualidade de Vida/psicologia , Percepção Social , Estigma Social , Idoso , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax design was used. During phase I, no dose-limiting toxicities were shown in three patients who received GM.CD40L.CCL21. During phase II, of evaluable patients, 5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus GM.DCD40L.CCL21 (95% CI 0.70-2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21, the most common treatment-related adverse events (TRAEs) were grade 1/2 injection site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%). Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence of pseudo-progression or immune-related TRAEs of grade 1 or greater of pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to toxicity. Although we found no significant associations between vaccine immunogenicity and outcomes, in limited biopsies, one patient treated with GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible effectiveness warrants further investigation of GM.CD40L in combination approaches.
Assuntos
Adenocarcinoma/terapia , Ligante de CD40/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiocina CCL21/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Imunoterapia , Adenocarcinoma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Alectinib--a highly selective, CNS-active, ALK inhibitor-showed promising clinical activity in crizotinib-naive and crizotinib-resistant patients with ALK-rearranged (ALK-positive) non-small-cell lung cancer (NSCLC). We aimed to assess the safety and efficacy of alectinib in patients with ALK-positive NSCLC who progressed on previous crizotinib. METHODS: We did a phase 2 study at 27 centres in the USA and Canada. We enrolled patients aged 18 years or older with stage IIIB-IV, ALK-positive NSCLC who had progressed after crizotinib. Patients were treated with oral alectinib 600 mg twice daily until progression, death, or withdrawal. The primary endpoint was the proportion of patients achieving an objective response by an independent review committee using Response Evaluation Criteria in Solid Tumors, version 1.1. Response endpoints were assessed in the response-evaluable population (ie, patients with measurable disease at baseline who received at least one dose of study drug), and efficacy and safety analyses were done in the intention-to-treat population (all enrolled patients). This study is registered with ClinicalTrials.gov, number NCT01871805. The study is ongoing and patients are still receiving treatment. FINDINGS: Between Sept 4, 2013, and Aug 4, 2014, 87 patients were enrolled into the study (intention-to-treat population). At the time of the primary analysis (median follow-up 4·8 months [IQR 3·3-7·1]), 33 of 69 patients with measurable disease at baseline had a confirmed partial response; thus, the proportion of patients achieving an objective response by the independent review committee was 48% (95% CI 36-60). Adverse events were predominantly grade 1 or 2, most commonly constipation (31 [36%]), fatigue (29 [33%]), myalgia 21 [24%]), and peripheral oedema 20 [23%]). The most common grade 3 and 4 adverse events were changes in laboratory values, including increased blood creatine phosphokinase (seven [8%]), increased alanine aminotransferase (five [6%]), and increased aspartate aminotransferase (four [5%]). Two patients died: one had a haemorrhage (judged related to study treatment), and one had disease progression and a history of stroke (judged unrelated to treatment). INTERPRETATION: Alectinib showed clinical activity and was well tolerated in patients with ALK-positive NSCLC who had progressed on crizotinib. Therefore, alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib. FUNDING: F Hoffmann-La Roche.
Assuntos
Antineoplásicos/uso terapêutico , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piperidinas/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Quinase do Linfoma Anaplásico , Antineoplásicos/efeitos adversos , Aspartato Aminotransferases/sangue , Carbazóis/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Constipação Intestinal/induzido quimicamente , Creatina Quinase/sangue , Crizotinibe , Resistencia a Medicamentos Antineoplásicos , Edema/induzido quimicamente , Fadiga/induzido quimicamente , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , Piperidinas/efeitos adversos , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/análise , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Critérios de Avaliação de Resposta em Tumores Sólidos , RetratamentoRESUMO
LESSONS LEARNED: Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials.Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC.Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients. BACKGROUND: Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. METHODS: In this phase II study, 8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0-2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinib was allowed at progression. RESULTS: Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5-3.6) and 1.2 (95% CI, 1.1-1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2-7.6) and 3.4 (95% CI, 1.8-5.6) months for topotecan and linsitinib, respectively (p = .71). Grade 3/4 adverse events (>5% incidence) included anemia, thrombocytopenia, neutropenia/leukopenia, diarrhea, fatigue, dehydration, and hypokalemia for topotecan; and thrombocytopenia, fatigue, and alanine aminotransferase/aspartate aminotransferase elevations for linsitinib. CONCLUSION: Linsitinib was safe but showed no clinical activity in unselected, relapsed SCLC patients.
Assuntos
Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Pirazinas/uso terapêutico , Receptor IGF Tipo 1/antagonistas & inibidores , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imidazóis/efeitos adversos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Pirazinas/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Topotecan/efeitos adversosRESUMO
BACKGROUND: Uterine carcinosarcoma, a rare gynecological malignancy, often presents at the advanced stage with a poor prognosis because current therapies have not improved rates of survival. Genetic characterization of this tumor may lead to novel, specifically targeted drug targets to provide better treatment options for patients with this malignancy. METHODS: We present a case of a woman aged 61 years with uterine carcinosarcoma and retrospectively analyzed 100 study patients with uterine carcinosarcoma. From this group, 9 study patients underwent targeted sequencing of 1,321 genes. RESULTS: All 9 study patients had at least 1 mutation in JAK2, KRAS, PIK3CA, CTNNB1, PTEN, FBXW7, TP53, and ERBB2; of these, TP53 was the most frequently mutated gene (6/9). In addition, ARID1A and KMT2C, which have been described and identified as part of a set of chromatin-remodeling genes, were also found in our analyses. From our 100-person cohort clinical analyses, study patients with stage 1 cancer had a median survival rate of 33 months (95% confidence interval, 19-109) compared with a median survival rate of 6 months (95% confidence interval, 3-12) in those with stage 4 disease. CONCLUSIONS: Disease stage alone predicted the rate of clinical survival. Up to 50% in the study group were identified at having early stage disease (stage 1/2), indicating improved rates of overall detection compared with previously reported data. Our mutational analysis findings add to the number of tumors in which these mutations have been found and suggest that chromatin-remodeling dysregulation may play a role in the tumorigenesis of carcinosarcoma.
Assuntos
Carcinogênese/genética , Carcinossarcoma/genética , Montagem e Desmontagem da Cromatina/genética , Neoplasias Uterinas/genética , Idoso , Carcinossarcoma/diagnóstico por imagem , Carcinossarcoma/patologia , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologiaRESUMO
Immune checkpoint inhibitors produce durable long-term survival in some patients with advanced melanoma and lung cancer. Better immune targets and combination strategies can harness the immune system by supporting the three elements of a successful T-cell antitumor response: (A) generation of sufficient numbers of antitumor T cells within the lymphoid compartment; (B) effective T-cell trafficking and extravasation out of the lymphoid compartment, through the bloodstream, and into the tumor microenvironment; and (C) T-cell effector function within the tumor microenvironment that is characterized by the ability to bypass immune checkpoints, soluble and metabolic inhibitory factors, and inhibitory cells. Strategies that hold promise include dual immune checkpoint blockade, as well as the combination of immune checkpoint blockade with costimulatory receptor agonists, enhancers of innate immunity, inhibition of indoleamine 2,3-dioxygenase, adoptive T-cell transfer/T-cell engineering, therapeutic vaccines, small-molecule inhibitors, and radiation therapy. Novel, rational clinical trial designs seek to combine targeted agents and one or more immune checkpoint inhibitors, with the goal of producing deep and durable antitumor responses, which thus far have been observed in only a minority of patients.
Assuntos
Terapia Combinada/métodos , Terapia Combinada/tendências , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias/imunologia , Neoplasias/terapia , HumanosRESUMO
BACKGROUND: Patients with non-small-cell lung cancer (NSCLC) and ALK rearrangements generally have a progression-free survival of 8-11 months while on treatment with the ALK inhibitor crizotinib. However, resistance inevitably develops, with the brain a common site of progression. More potent ALK inhibitors with consistently demonstrable CNS activity and good tolerability are needed urgently. Alectinib is a novel, highly selective, and potent ALK inhibitor that has shown clinical activity in patients with crizotinib-naive ALK-rearranged NSCLC. We did a phase 1/2 study of alectinib to establish the recommended phase 2 dose of the drug and examine its activity in patients resistant or intolerant to crizotinib. METHODS: We enrolled patients with ALK-rearranged NSCLC who progressed on or were intolerant to crizotinib. We administered various oral doses of alectinib (300-900 mg twice a day) during the dose-escalation portion of the study (phase 1), to ascertain the recommended dose for phase 2. We used Response Evaluation Criteria in Solid Tumors criteria (version 1.1) to investigate the activity of alectinib in all patients with a baseline scan and at least one post-treatment scan (CT or MRI), with central radiological review of individuals with brain metastases. We assessed safety in all patients who received at least one dose of alectinib. Here, we present data for the phase 1 portion of the study, the primary objective of which was to establish the recommended phase 2 dose; phase 2 is ongoing. This trial is registered at ClinicalTrials.gov, number NCT01588028. FINDINGS: 47 patients were enrolled. Alectinib was well tolerated, with the most common adverse events being fatigue (14 [30%]; all grade 1-2), myalgia (eight [17%]; all grade 1-2), and peripheral oedema (seven [15%] grade 1-2, one [2%] grade 3). Dose-limiting toxic effects were recorded in two patients in the cohort receiving alectinib 900 mg twice a day; one individual had grade 3 headache and the other had grade 3 neutropenia. The most common grade 3-4 adverse events were increased levels of γ-glutamyl transpeptidase (two [4%]), a reduction in the number of neutrophils (two [4%]), and hypophosphataemia (two [4%]). Three patients reported four grade 4 serious adverse events that were deemed unrelated to alectinib: acute renal failure; pleural effusion and pericardial effusion; and brain metastasis. At data cut-off (median follow-up 126 days [IQR 84-217]), 44 patients could be assessed for activity. Investigator-assessed objective responses were noted in 24 (55%) patients, with a confirmed complete response in one (2%), a confirmed partial response in 14 (32%), and an unconfirmed partial response in nine (20%). 16 (36%) patients had stable disease; the remaining four (9%) had progressive disease. Of 21 patients with CNS metastases at baseline, 11 (52%) had an objective response; six (29%) had a complete response (three unconfirmed) and five (24%) had a partial response (one unconfirmed); eight (38%) patients had stable disease and the remaining two (10%) had progressive disease. Pharmacokinetic data indicated that mean exposure (AUC0-10) after multiple doses of alectinib (300-600 mg twice a day) was dose-dependent. INTERPRETATION: Alectinib was well tolerated, with promising antitumour activity in patients with ALK-rearranged NSCLC resistant to crizotinib, including those with CNS metastases. On the basis of activity, tolerability, and pharmacokinetic data, we chose alectinib 600 mg twice a day as the recommended dose for phase 2. FUNDING: Chugai Pharmaceuticals, F Hoffmann La-Roche.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Piperidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Neoplasias Encefálicas/mortalidade , Carbazóis/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Crizotinibe , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Seleção de Pacientes , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Lung cancer is the leading cause of cancer mortality. Non-small-cell lung cancer (NSCLC) comprises up to 90% of all lung cancers. Conventional treatment for advanced NSCLC consists of chemotherapy and has a small impact on survival. Molecular targets, such as epidermal growth factor receptor (EGFR), involved in cell signaling have led to the development of new, targeted therapies over the past 15 years. METHODS: Using a case report from our clinical practice, we review the literature and provide guidelines to the approach and management of advanced EGFR mutation-positive NSCLC. RESULTS: Targeted and/or biologic (small molecules or monoclonal antibodies) cancer therapies have vaulted to the forefront of clinical research and therapeutic use. Our recommendation, backed by strong scientific evidence, is to treat patients with advanced or recurrent NSCLC harboring activating EGFR mutation with an EGFR tyrosine kinase inhibitor (TKI) as early as possible. Erlotinib is currently the drug of choice in the United States, although afatinib, due to its recent approval by the US Food and Drug Administration, will soon be available. CONCLUSIONS: Improved understanding of cell signaling pathways that control cellular proliferation, differentiation, and survival combined with our increased ability to screen for specific mutations that drive malignant transformation and oncogenic behavior, has altered our treatment of advanced NSCLC. We can now provide a more individualized approach associated with improved progression-free survival and quality of life.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Terapia de Alvo MolecularRESUMO
BACKGROUND: Genomic or proteomic profiling of cancer can be broadly defined as a systematic grouping of cancer based on its genetic or protein makeup. In the management of non-small-cell lung cancer (NSCLC), genomic and proteomic profiling applications have become useful in early disease detection, diagnosis, treatment, and prognostication. METHODS: We reviewed the recent literature on the applications of genomic and proteomic profiling in NSCLC. Important applications were summarized into those already adopted as standard care and those still under investigation. RESULTS: For genomic profiling, testing for EGFR mutation and ALK rearrangement has become routine for adenocarcinoma. Multiplex assay and malignancy-risk gene signature are both important applications in development. A test to predict outcome after treatment with an epidermal growth factor rector/tyrosine kinase inhibitor and a screening blood test for lung cancer are being investigated for use in proteomic profiling. CONCLUSIONS: Genomic profiling is routine in patients with NSCLC, and proteomic profiling shows promise. Additional genomic and proteomic profiling applications may also prove to be useful contributions in the care of these patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Genômica/métodos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Proteômica/métodosRESUMO
BACKGROUND: Plinabulin is a GEF-H1 releasing agent with an immune-enhancing function. We report results from a multicenter Phase I/II study (NCT03575793) assessing plinabulin in combination with nivolumab and ipilimumab for the treatment of recurrent SCLC. METHODS: In Phase I, patients were enrolled using a 3 + 3 design to determine dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D). Patients received nivolumab (1 mg/kg), ipilimumab (3 mg/kg), and plinabulin (in escalating doses) on day 1 of each 21-day cycle for 4 cycles followed by maintenance with plinabulin and nivolumab. In phase II, patients with recurrent PD(L)1 inhibitor resistant SCLC were enrolled. The primary objective was median progression-free survival (PFS). RESULTS: Between 9/2018 and 2/2023, 39 patients were enrolled, and 36 patients received study treatment and were evaluable for safety (16 in Phase I; 20 in Phase II). In the phase I dose-escalation, there were 2 DLTs; grade 3 altered mental status lasting <24 h and grade 3 infusion reaction. The Plinabulin RP2D was determined to be 30 mg/m2. Common TRAEs were vomiting (44 %), nausea (42 %), and infusion reaction (36 %); 6 % of patients had a ≥grade 3 TRAE. Five patients (14 %) had ≥grade 3 irAEs; there were no cases of immune-related pneumonitis. In the efficacy analysis in 27 patients, the median PFS was 1.6 months (95 % CI 1.2 to 2.7) and the trial did not meet the pre-specified target median PFS of 3.5 months. Four patients treated at 30 mg/m2 had PR (confirmed 1, unconfirmed 3); 5 patients had SD with a CBR of 33 %. Two of 8 patients treated in phase I at the lower 20 mg/m2 dose had confirmed PR, with 1 patient on the drug regimen for >90 cycles. The median OS and follow-up time were 5.5 months and 2.5 months respectively. CONCLUSIONS: Plinabulin in combination with nivolumab and ipilimumab was tolerable at the dose of 30 mg/m2. While the clinical responses in PD-1 resistant SCLC were limited, some patients had a long duration of response. The number of ≥grade 3 irAE with the combination were lower than expected.
RESUMO
Myeloid-derived suppressor cells (MDSC) are one of the major factors limiting the efficacy of immune therapy. In a clinical trial of patients with extensive stage small cell lung cancer (SCLC), we tested the possibility that targeting MDSC can improve the induction of immune responses by a cancer vaccine. Forty-one patients with extensive stage SCLC were randomized into three arms: arm A--control, arm B--vaccination with dendritic cells transduced with wild-type p53, and arm C--vaccination in combination with MDSC targeted therapy with all-trans-retinoic acid (ATRA). Interim results of the ongoing clinical trial are presented. Pre-treatment levels of MDSC populations in patients from all three arms were similar. Vaccine alone did not affect the proportion of MDSC, whereas in patients treated with ATRA, the MDSC decreased more than twofold (p = 0.02). Before the start of treatment, no patients had detectable p53-specific responses in IFN-γ ELISPOT. Sequential measurements did not show positive p53 responses in any of the 14 patients from arm A. After immunization, only 3 out of 15 patients (20 %) from arm B developed a p53-specific response (p = 0.22). In contrast, in arm C, 5 out of 12 patients (41.7 %) had detectable p53 responses (p = 0.012). The proportion of granzyme B-positive CD8(+) T cells was increased only in patients from arm C but not in arm B. Depletion of MDSC substantially improved the immune response to vaccination, suggesting that this approach can be used to enhance the effect of immune interventions in cancer.
Assuntos
Vacinas Anticâncer/uso terapêutico , Neoplasias Pulmonares/imunologia , Carcinoma de Pequenas Células do Pulmão/imunologia , Idoso , Citocinas/metabolismo , Células Dendríticas/citologia , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Células Mieloides/citologia , Fenótipo , Carcinoma de Pequenas Células do Pulmão/terapia , Tretinoína/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease. METHODS: Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2). RESULTS: The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination. CONCLUSION: V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2. TRIAL REGISTRATION: Study 1 - ClinicalTrials.gov, NCT00250419; Study 2 - ClinicalTrials.gov, NCT00647114.
Assuntos
Adenoviridae/genética , Vacinas Anticâncer/uso terapêutico , Antígeno Carcinoembrionário/genética , Genes erbB-2 , Neoplasias/terapia , Vacinas de DNA/uso terapêutico , Idoso , Vacinas Anticâncer/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Feminino , Vetores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Plasmídeos , Vacinas de DNA/efeitos adversosRESUMO
BACKGROUND: Lung cancer is the most common cause of cancer-related death in the United States, yet traditional chemotherapy fails to provide long-term benefit for many patients. New approaches are needed to improve overall survival beyond the current standard of care. METHODS: This review discusses recent clinical trials using immunotherapy techniques to treat both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) and highlights ongoing immunotherapy research efforts at our center. RESULTS: For NSCLC, phase II clinical trials have examined allogeneic vaccines that target either mucin 1 (MUC1), epidermal growth factor or melanoma-associated antigen 3. These vaccines are now undergoing larger phase III trials. An autologous cellular therapy directed against transforming growth factor beta-2 and a recombinant protein with antitumor properties have also shown promise in prolonging survival in NSCLC in phase II trials. The monoclonal antibodies ipilimumab, BMS-936558 (anti-PD-1), and BMS936559 (anti-PD-L1) lead to enhanced T-cell-mediated antitumor effects and have produced objective responses in early-phase clinical trials. Studies for SCLC also exist, such as a novel vaccine therapy targeting p53. CONCLUSIONS: Recent clinical trials in lung cancer demonstrate the potential of immunotherapeutics to increase overall survival in patients with lung cancer compared with the current standard of care.