RESUMEN
IMPORTANCE: This study demonstrates that tislelizumab in combination with chemotherapy is associated with improved progression-free survival (PFS) in patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). OBJECTIVE: To assess the efficacy and safety/tolerability of tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for patients with advanced sq-NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This open-label, randomized phase 3 clinical trial was conducted at 46 sites in China between July 2018 and June 2019 and included patients with treatment-naive, histologically confirmed stage IIIB/IV sq-NSCLC. The data cutoff for these analyses was December 6, 2019; data extraction occurred on January 7, 2020. INTERVENTIONS: Patients were randomized (1:1:1) to receive 1 of the following regimens intravenously on a 21-day cycle: tislelizumab (200 mg, day 1) plus paclitaxel (175 mg/m2, day 1) and carboplatin (area under the concentration of 5, day 1) (arm A); tislelizumab plus nab-paclitaxel (100 mg/m2, days 1, 8, and 15) and carboplatin (arm B); and paclitaxel and carboplatin (arm C). Patients were stratified by disease stage and tumor programmed cell death 1 ligand 1 (PD-L1) expression (<1% vs 1%-49% vs ≥50%). MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary end points included overall survival, investigator-assessed (INV) PFS, IRC-assessed objective response rate (ORR), and IRC-assessed duration of response, as well as the incidence and severity of adverse events (AEs). RESULTS: Overall, 355 patients (median [range] age, 62 [34-74] years; 330 men [91.7%]) with sq-NSCLC received treatment. After a median study follow-up of 8.6 months (95% CI, 8.1-9.0 months), IRC-assessed PFS was significantly improved with tislelizumab plus chemotherapy (arm A, 7.6 months; arm B, 7.6 months) vs chemotherapy alone (arm C, 5.5 months; hazard ratios were 0.524 (95% CI, 0.370-0.742; P < .001 [A vs C]) and 0.478 (95% CI, 0.336-0.679; P < .001 [B vs C]). Higher IRC-assessed ORR and longer IRC-assessed duration of response were observed in arms A (72.5%; 8.2 months) and B (74.8%; 8.6 months) vs C (49.6%; 4.2 months). No association was observed between PD-L1 expression and IRC-assessed PFS or ORR. Discontinuation of any treatment because of AEs was reported in 15 (12.5%; arm A), 35 (29.7%; arm B), and 18 (15.4%; arm C) patients. In each arm, the most common grade of 3 or greater AE was decreased neutrophil levels, which aligned with known chemotherapy toxic effects. Six treatment-related AEs leading to death occurred; however, no deaths were solely attributed to tislelizumab. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, adding tislelizumab to chemotherapy was associated with significantly prolonged IRC-assessed PFS, higher IRC-assessed ORRs, and a manageable safety/tolerability profile in patients with advanced sq-NSCLC, regardless of PD-L1 expression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03594747.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/patología , Paclitaxel/efectos adversosRESUMEN
In this article, inconsistency of the association of polymorphisms of fibroblast growth factor receptor 2 (FGFR2) with breast cancer is noted. Three commonly studied FGFR2 polymorphisms including rs1219648 (A > G), rs2420946 (C > T), and rs2981582 (C > T) were selected to explore their association with risk of development of breast cancer by meta-analysis of published case-control studies. The results showed that all these three polymorphisms were significantly associated with altered breast cancer risk in any model (co-dominant, dominant, or recessive model) and in stratification based on ethnicity and study design. In the subgroup analyses for postmenopausal women, significantly increased risks were found for rs1219648 and rs2420946 in any model. This meta-analysis suggests that FGFR2 is likely an important genetic marker contributing to susceptibility of breast cancer. We recommend that these single nucleotide polymorphisms to be included in future association studies and functional assays.
Asunto(s)
Neoplasias de la Mama/genética , Polimorfismo de Nucleótido Simple , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Estudios de Casos y Controles , Medicina Basada en la Evidencia , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Oportunidad Relativa , Medición de Riesgo , Factores de RiesgoAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Pemetrexed/uso terapéuticoRESUMEN
To analyze the clinical characteristics, results of treatment, and prognostic factors of patients diagnosed as primary ovarian non-Hodgkin's lymphoma (PONHL). Fourteen cases of PONHL treated in Fudan University Cancer Center during a 10-year period were retrospectively reviewed, and the clinical data of the patients were analyzed for correlation between KPS, clinical stage, tumor size, IPI, ovary involvement, treatment and prognosis. The median age was 45 years, and thirteen patients were diagnosed of diffuse large B-cell lymphoma and one patient lymphoblastic lymphoma. Four patients were stage IE, three stage IIE, and seven stage IVE. The median tumor size was 8 cm (range, 4.0-15.0 cm). The median overall survival (OS) of the 14 patients was 23.0 months (range 11.5-71.2 months). Thirty-six percentage of patients with bilateral ovary involvement had a shorter survival time than those with unilateral ovary involvement (median OS: 19.0 vs. 37.2 months, P=0.014). The OS of Stage IVE was worse than stage IE and stage IIE (median OS: 18.75 vs. 37.5 months, P=0.047). Patients with IPI>2 had worse prognosis than those with IPI≤2 (median OS: 19.0 vs. 42.1 months, P=0.03). PONHL patient with larger tumor mass had worse prognosis (median OS: 19.1 vs. 37.2 months, P=0.019). R-CHOP regimens had a tendency to improve the OS but was not shown to be statistically significant (median OS: 22.4 vs. 37.2 months, P=0.436). The management of PONHL should be based on multi-modality treatment including surgery and chemotherapy. The significant prognostic factors of survival are tumor size, Ann Arbor staging, and IPI.
Asunto(s)
Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Femenino , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Linfoma no Hodgkin/tratamiento farmacológico , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Prednisona , Pronóstico , Estudios Retrospectivos , Rituximab , VincristinaRESUMEN
To derive a more precise estimation of the relationship between the xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and lung cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the XPD Asp312Asn polymorphism and lung cancer risk. The pooled ORs were performed with co-dominant model (Asp/Asn vs. Asp/Asp, Asn/Asn vs. Asp/Asp), dominant model (Asp/Asn + Asn/Asn vs. Asp/Asp), and recessive model (Asn/Asn vs. Asp/Asp+Asp/Asn), respectively. A total of 18 studies including 7,552 cases and 9,397 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with XPD Asn allele when all studies were pooled into the meta-analysis (Asn/Asn vs. Asp/Asp: OR=1.158, 95% CI=1.018-1.317; recessive model: OR=1.161, 95% CI=1.029-1.311). In the subgroup analysis by ethnicity, significantly increased risks were found for both Caucasians (Asn/Asn vs. Asp/Asp: OR=1.164, 95% CI=1.003-1.351; recessive model: OR=1.169, 95% CI=1.016-1.345) and Asians (Asn/Asn vs. Asp/Asp: OR=8.056, 95% CI=2.420-26.817; recessive model: OR=7.956, 95% CI=2.391-26.477). When stratified by study design, statistically significantly elevated risk was noted in hospital-based studies (Asn/Asn vs. Asp/Asp: OR=1.315, 95% CI=1.110-1.558; recessive model: OR=1.290, 95% CI=1.099-1.513). In conclusion, this meta-analysis suggests that the XPD Asn allele is a low-penetrant risk factor for developing lung cancer.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Humanos , Oportunidad Relativa , Factores de RiesgoRESUMEN
The hepatitis B virus (HBV) reactivation rate among hepatitis B virus surface antigen (HBsAg)-positive patients undergoing chemotherapy ranges from 21 to 35% with a mortality rate of 4-41%. The risk is significantly evident in patients with aggressive lymphoma, which is highly responsive to standard chemotherapy with cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP) achieving a complete response rate of 60-80% and 5-year survival rate of 30-50% with only 1% of treatment-related mortality. Alpha-Interferon and lamivudine were given as preemptive treatment for HBV reactivation in HBsAg-positive patients treated for aggressive lymphoma consecutively from 1994 to 1997 and 1998 to 2001, respectively, in our institution. The outcome of 77 HBsAg-positive patients treated for aggressive lymphoma at our institution from 1990 to 2001 was studied. Of these patients, 53 did not receive prophylaxis while 13 received subcutaneous alpha-interferon 3 x 10(6) U thrice weekly and 11 received oral lamivudine 100 mg/day simultaneously with chemotherapy. Seventeen patients in the non-prophylactic group experienced HBV reactivation (32%), seven of whom progressed to fatal fulminant hepatitis (41%), which is associated with 13.2% of the mortality rate among the non-prophylactic patients. None of the 24 patients in the prophylactic group had grade III or IV toxicity or elevated ALT level greater than fivefold exceeding 200 IU/l suggestive of clinical hepatitis that required dose reduction or delayed chemotherapy. Thus, preemptive use of alpha-interferon or lamivudine in HBsAg-positive lymphoma patients undergoing chemotherapy may be a promising approach to prevent HBV reactivation that carries a risk of delayed treatment or even fatal outcome.