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2.
Curr Oncol ; 31(5): 2453-2480, 2024 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-38785465

RESUMO

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how "incremental cost-effectiveness ratios" (ICERs) based on measures such as gains in "quality-adjusted life-years" (QALYs) may be used to determine a drug's value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.


Assuntos
Antineoplásicos , Análise Custo-Benefício , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/economia , Análise Custo-Benefício/métodos , Canadá , Anos de Vida Ajustados por Qualidade de Vida , Custos de Medicamentos , COVID-19 , Neoplasias/tratamento farmacológico , Neoplasias/economia , SARS-CoV-2
4.
Curr Oncol ; 31(2): 1028-1034, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38392070

RESUMO

Malignant pleural mesothelioma is a rare, aggressive, and incurable cancer with a poor prognosis and high symptom burden. For these patients, little is known about the impact of palliative care consultation on outcomes such as mortality, hospital admissions, or emergency department visits. The aim of this study is to determine if referral to supportive and palliative care in patients with malignant pleural mesothelioma is associated with survival and decreased hospital admissions and emergency department visits. This is a retrospective chart review. Study participants include all malignant pleural mesothelioma patients seen at The Ottawa Hospital-an acute care tertiary center-between January 2002 and March 2019. In total, 223 patients were included in the study. The mean age at diagnosis was 72.4 years and 82.5% were male. Of the patients diagnosed between 2002 and 2010, only 11 (9.6%) were referred to palliative care. By comparison, of those diagnosed between 2011 and 2019, 49 (45.4%) were referred to palliative care. Median time from diagnosis to referral was 4.1 months. There was no significant difference in the median survival of patients referred for palliative care compared to those who did not receive palliative care (p = 0.46). We found no association between receiving palliative care and the mean number of hospital admissions (1.04 vs. 0.91) from diagnosis to death, and an increase in mean number of emergency department visits in the palliative care group (2.30 vs. 1.18). Although there was increased utilization of palliative care services, more than half of the MPM patients did not receive palliative care despite their limited survival. There was an increase in emergency department visits in the palliative care group; this may represent an increase in the symptom burden (i.e., indication bias) in those referred to palliative care.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Masculino , Feminino , Mesotelioma Maligno/terapia , Cuidados Paliativos , Mesotelioma/terapia , Mesotelioma/patologia , Estudos Retrospectivos , Neoplasias Pleurais/terapia , Neoplasias Pleurais/patologia , Morte
5.
Nat Med ; 30(3): 716-729, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38351187

RESUMO

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab-ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6-7.4) versus 2.7 (1.8-2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1-20.3) versus 9.4 (7.5-10.6) months. Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab-ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Morfolinas , Pirimidinas , Sulfonamidas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Platina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais , Antineoplásicos/uso terapêutico , Biomarcadores , Antígeno B7-H1 , Microambiente Tumoral
6.
Nat Med ; 29(10): 2559-2569, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37814061

RESUMO

Circulating tumor DNA (ctDNA) has shown promise in capturing primary resistance to immunotherapy. BR.36 is a multi-center, randomized, ctDNA-directed, phase 2 trial of molecular response-adaptive immuno-chemotherapy for patients with lung cancer. In the first of two independent stages, 50 patients with advanced non-small cell lung cancer received pembrolizumab as standard of care. The primary objectives of stage 1 were to ascertain ctDNA response and determine optimal timing and concordance with radiologic Response Evaluation Criteria in Solid Tumors (RECIST) response. Secondary endpoints included the evaluation of time to ctDNA response and correlation with progression-free and overall survival. Maximal mutant allele fraction clearance at the third cycle of pembrolizumab signified molecular response (mR). The trial met its primary endpoint, with a sensitivity of ctDNA response for RECIST response of 82% (90% confidence interval (CI): 52-97%) and a specificity of 75% (90% CI: 56.5-88.5%). Median time to ctDNA response was 2.1 months (90% CI: 1.5-2.6), and patients with mR attained longer progression-free survival (5.03 months versus 2.6 months) and overall survival (not reached versus 7.23 months). These findings are incorporated into the ctDNA-driven interventional molecular response-adaptive second stage of the BR.36 trial in which patients at risk of progression are randomized to treatment intensification or continuation of therapy. ClinicalTrials.gov ID: NCT04093167 .


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados , Intervalo Livre de Progressão
7.
Cancer ; 129(23): 3815-3819, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37665180

RESUMO

BACKGROUND: Paclitaxel has a risk of infusion-related reactions (IRRs) and despite no prospective evidence, is often given with premedication including a corticosteroid, H1 antagonist, and H2 antagonist (H2RA). Backorders impacted the supply of intravenous H2RAs at our center, and it was removed as routine premedication. The authors compared the incidence of IRR in patients treated without H2RA to patients receiving standard H2RA premedication. METHODS: The authors reviewed outpatients starting paclitaxel at the Ottawa Hospital from December 2019 to October 2021. Two cohorts were created: patients treated without H2RA premedication (intervention), and those receiving standard H2RA (control). Demographics, treatment, and IRR information were collected retrospectively. Primary end point was rate of grade ≥2 IRRs during first two doses of paclitaxel. RESULTS: A total of 182 patients were treated without H2RA premedication, compared to 184 control patients treated during non-backorder periods. Baseline characteristics included: median age, 63 years; 86% female; and primary tumor 52% breast/24% gynecologic/10% gastric/esophageal/8% lung/6% other. There were no significant differences between cohorts in baseline characteristics. There was no difference in the rate of grade ≥2 IRR between cohorts; 12.1% (22 of 182; 95% confidence interval [CI], 7.7%-17.7%) for patients treated without H2RA, and 15.1% (28 of 185; 95% CI, 10.3%-21.1%) for control patients. The rate of grade ≥3 IRRs were also similar, 4.4% in intervention cohort versus 3.8% in control cohort. CONCLUSIONS: The removal of H2RAs from premedication for paclitaxel did not result in an increased incidence of IRRs. The use of H2RAs in preventing IRRs to paclitaxel should be re-evaluated.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Paclitaxel , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Pré-Medicação
8.
Curr Oncol ; 30(9): 8363-8374, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37754522

RESUMO

BACKGROUND: Limited research exists regarding how healthcare stakeholders prioritize the importance of differing physician attributes in oncologists. Identifying these priorities can help ensure that Canadian cancer care continues to meet the needs of its patients. In our previous research, compassion and empathy were identified as important physician attributes, with answers like knowledge, professionalism or communication less common. We hypothesized that respondents may have been assuming other, underlying qualities in their oncologists when they prioritized "compassion" and "empathy". To test this, the current study asks respondents to rank important physician attributes. METHODS: With ethics approval, we asked healthcare stakeholders (physicians, nurses, patients, caregivers, medical students, and allied healthcare providers) to rank the eight most popular qualities or attributes. We identified differences between which characteristics each group valued most in physicians. RESULTS: 375 respondents participated in the survey. "Knowledge" and "competence" were the most popular answers in the current study among all groups except medical students. CONCLUSION: Previously, we identified compassion as a highly valued attribute; however, this survey suggests that this may be with the assumption that a physician is knowledgeable and competent. Future research will use semi-structured interviews to investigate respondents' rationales for making their choices and help interpret our findings in this study.


Assuntos
Neoplasias , Médicos , Humanos , Atitude do Pessoal de Saúde , Canadá , Relações Médico-Paciente , Inquéritos e Questionários , Neoplasias/terapia
9.
JCO Oncol Pract ; 19(9): 819-827, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37582243

RESUMO

PURPOSE: Medical assistance in dying (MAiD) was legalized in Canada in 2016. To date, patients with cancer account for 69% of MAiD deaths, yet little information is available about these patients. We reviewed disease and treatment characteristics of patients with cancer who underwent MAiD to better understand this population and identify gaps in our current system of care. MATERIALS AND METHODS: Patients with cancer who underwent MAiD through the Champlain Regional MAiD Network from June 2016 to November 2020 were reviewed. Baseline demographic, diagnostic, and treatment details were collected by retrospective review. RESULTS: During the study period, 255 patients with cancer underwent MAiD. At the time of MAiD, 201 patients (79%) had metastatic disease. Most prevalent solid organ tumors were gastrointestinal (30%), lung (18%) and genitourinary (14%). MAiD was primarily provided in the home (48%) or an acute inpatient facility (40%). One hundred eighty-nine (74%) patients were evaluated by medical oncology, 23 by gynecology oncology (9%), 11 by hematology oncology (4%), and 177 (69%) by radiation oncology. One hundred fifty-eight (62%) patients were not seen by oncology specialists in the 30 days prior to MAiD. One hundred fifty-nine patients (62%) had at least one line of systemic therapy, 138 patients (54%) received radiotherapy, and 61 patients (24%) did not receive cancer-directed treatment. Palliative care assessed at least 213 patients (84%). Common reasons for pursuing MaiD included disease-related symptoms (33%), fear of future suffering or disability (19%), and the ability to control the time and manner of death (17%). In 36% of cases, the reason was not documented. CONCLUSION: Although formal oncology consultation is not required before MAiD, with an ever-increasing number of novel cancer therapies, oncologists, cancer centers, and MAiD providers should consider collaborating to ensure a streamlined assessment process for patients.


Assuntos
Neoplasias , Suicídio Assistido , Humanos , Canadá/epidemiologia , Cuidados Paliativos , Neoplasias/epidemiologia , Neoplasias/terapia , Assistência Médica
10.
Curr Oncol ; 30(7): 6006-6018, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37504310

RESUMO

Concurrent chemoradiotherapy (CRT) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). Local therapy-surgery or stereotactic body radiotherapy (SBRT)-with adjuvant chemotherapy may be appropriate for very early (T1-T2, N0) disease. There is variability in the management of these cases, which may lead to variability in patient outcomes. This study aimed to determine practice patterns for the management of very early LS-SCLC in Canada. A survey was developed and distributed to Canadian medical and radiation oncologists specialising in lung cancer. The survey consisted of three sections: (1) physician demographics, (2) general practice approach, and (3) preferred approach for three clinical scenarios (1: peripheral T1 lesion; 2: central T1 lesion; 3: peripheral T2 lesion). Responses were analysed to detect differences across cases and among physician groups. There were 77 respondents. In case 1, assuming medical operability, most respondents (73%) chose surgery and adjuvant chemotherapy, with 19% choosing CRT. CRT was selected by a higher proportion in case 2 (48%) and case 3 (61%) (p < 0.05). If medically inoperable, most chose CRT over local therapy in all cases, with more choosing CRT in case 2 (84%) and case 3 (86%) than in case 1 (55%) (p < 0.05). Subgroup analysis showed a predilection towards CRT in Western Canada and among more experienced physicians, and towards SBRT in Ontario. There is variability in the management of very early LS-SCLC in Canada. CRT remains the most popular strategy in most cases, with surgery preferred for small peripheral lesions. Larger and more central tumours are more likely to be managed with CRT. Variation in practice is correlated with region and physician experience. Our study illustrates the variability in the management of very early LS-SCLC in Canada and highlights the need for more robust investigations into the ideal approach for these patients.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inquéritos e Questionários , Quimiorradioterapia , Ontário
11.
Curr Oncol ; 30(7): 6289-6315, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37504325

RESUMO

Small-cell lung cancer (SCLC) is an aggressive, neuroendocrine tumour with high relapse rates, and significant morbidity and mortality. Apart from advances in radiation therapy, progress in the systemic treatment of SCLC had been stagnant for over three decades despite multiple attempts to develop alternative therapeutic options that could improve responses and survival. Recent promising developments in first-line and subsequent therapeutic approaches prompted a Canadian Expert Panel to convene to review evidence, discuss practice patterns, and reach a consensus on the treatment of extensive-stage SCLC (ES-SCLC). The literature search included guidelines, systematic reviews, and randomized controlled trials. Regular meetings were held from September 2022 to March 2023 to discuss the available evidence to propose and agree upon specific recommendations. The panel addressed biomarkers and histological features that distinguish SCLC from non-SCLC and other neuroendocrine tumours. Evidence for initial and subsequent systemic therapies was reviewed with consideration for patient performance status, comorbidities, and the involvement and function of other organs. The resulting consensus recommendations herein will help clarify evidence-based management of ES-SCLC in routine practice, help clinician decision-making, and facilitate the best patient outcomes.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Canadá , Terapia Combinada , Consenso , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
12.
Curr Oncol ; 30(7): 6473-6496, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37504336

RESUMO

Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS), in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced KRAS G12C-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/- chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Canadá , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Consenso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética
13.
Curr Oncol ; 30(7): 6559-6574, 2023 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-37504341

RESUMO

Lorlatinib is the only targeted therapy approved in Canada to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose tumor has progressed despite treatment with second-generation ALK tyrosine kinase inhibitor (TKI), a patient population with high unmet need and lack of publicly reimbursed targeted treatments in Canada. We prospectively examined the real-world effectiveness and impact of lorlatinib on quality-of-life in 59 lorlatinib-treated patients, characterized as: median age of 62.0 years; 47.5% were female; 32.2% had central nervous system metastases; 50.8% had 2+ prior ALK TKI lines; and alectinib was the most common ALK TKI (72.9%) administered before lorlatinib, including 44.1% who received first-line alectinib. With a median follow-up of 15.3 months (IQR: 6.2-19.2), median time-to-treatment discontinuation of lorlatinib was 15.3 months (95% CI: 7.9-not reached), with 54.2% (95% CI: 40.8-65.9%) of patients without treatment discontinuation at 12 months. At baseline, the mean health utility score (HUS) was 0.744 (SD: 0.200). At 3 months, patients receiving lorlatinib demonstrated a 0.069 (95% CI: 0.020-0.118; p = 0.007) average HUS increase over baseline; HUS was maintained at 6 and 12 months. Thus, patients with ALK-positive NSCLC post second-generation ALK TKI remained on lorlatinib for a meaningful duration of time while their quality-of-life was preserved.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Canadá , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Lactamas Macrocíclicas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases , Qualidade de Vida
14.
Curr Oncol ; 30(4): 3817-3828, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-37185402

RESUMO

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Seguimentos , Quimiorradioterapia/métodos , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
16.
J Thorac Oncol ; 18(6): 813-819, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36841541

RESUMO

Immune checkpoint inhibitors have activity in mesothelioma. IND.227 was a phase 2 trial (120 patients planned) comparing progression-free survival of standard platinum and pemetrexed (CP) versus CP + pembrolizumab (pembro) versus pembro. Accrual to the pembro arm was discontinued on the basis of interim analysis (IA-16 wk disease control rate). CP + pembro was tolerable, with progression-free survival similar between arms and median survival and overall response rate higher than those of CP alone (19.8 mo [95% confidence interval or CI: 8.4-41.36] versus 8.9 mo [95% CI: 5.3-12.8] and 47% [95% CI: 24%-71%] versus 19% [95% CI: 5%-42%], respectively). The subsequent phase 3 trial has completed accrual; results are expected in 2023.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Neoplasias Pulmonares/patologia , Canadá , Mesotelioma/patologia , Pemetrexede/farmacologia , Pemetrexede/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pleurais/patologia
17.
JTO Clin Res Rep ; 4(12): 100601, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38162175

RESUMO

Background: Immunotherapy has vastly changed the treatment landscape for patients with advanced NSCLC. With high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), options include programmed cell death protein 1 or PD-L1 inhibitor with or without chemotherapy. A cut-point of greater than or equal to 50% defines PD-L1-high, but a more precise PD-L1 tumor proportion score may be an important predictor of outcomes. Methods: We reviewed all patients with PD-L1-high NSCLC who received pembrolizumab from June 2019 to June 2021. Demographic, diagnosis, treatment, and outcomes data were collected retrospectively. The primary end point was a descriptive analysis of pembrolizumab prescribing patterns. Secondary end points included overall survival (OS) by treatment choice and absolute PD-L1 expression. Results: Overall, 132 patients received pembrolizumab; 124 (94%) as monotherapy, and 8 (6%) with chemotherapy. Baseline characteristics include the following: (1) median age 70 years (50-89); (2) 55% men; (3) 79% Eastern Cooperative Oncology Group performance status 0 to 1; and (4) 96% current or former smokers. There were 39% who have PD-L1 greater than or equal to 90% versus 61% with PD-L1 of 50% to 89%. The median OS in the overall population was 14.4 months. The median OS in the pembrolizumab monotherapy cohort and combination cohort were 13.6 months and 16.6 months, respectively (p = 0.67). Within the monotherapy cohort, the median OS was longer for PD-L1 greater than or equal to 90% (19.8 mo) versus PD-L1 50% to 89% (11.9 mo, p = 0.039). The 24-month OS was 27.8% among patients with PD-L1 50% to 89% and 47.4% among patients with PD-L1 greater than or equal to 90%. Conclusions: Most patients with advanced PD-L1-high NSCLC received pembrolizumab monotherapy, among whom OS was strongly correlated with PD-L1 expression, with PD-L1 greater than or equal to 90% of patients experiencing substantially longer survival. PD-L1 expression level could be an important determinant in immunotherapy prescribing patterns and a predictor of success in advanced NSCLC.

18.
Curr Oncol ; 29(10): 7583-7586, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36290875

RESUMO

Lung cancer, because of the multiple subtypes now identifiable and because of the myriad of new and effective therapies, provides fertile ground to highlight issues related to oncology drug access in Canada [...].


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Canadá
19.
Ther Adv Med Oncol ; 14: 17588359221112696, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923926

RESUMO

Background: Liquid biopsy (LB) can detect actionable genomic alterations in plasma circulating tumor circulating tumor DNA beyond tissue testing (TT) alone in advanced non-small cell lung cancer (NSCLC) patients. We estimated the cost-effectiveness of adding LB to TT in the Canadian healthcare system. Methods: A cost-effectiveness analysis was conducted using a decision analytic Markov model from the Canadian public payer (Ontario) perspective and a 2-year time horizon in patients with treatment-naïve stage IV non-squamous NSCLC and ⩽10 pack-year smoking history. LB was performed using the comprehensive genomic profiling Guardant360™ assay. Standard of care TT for each participating institution was performed. Costs and outcomes of molecular testing by LB + TT were compared to TT alone. Transition probabilities were calculated from the VALUE trial (NCT03576937). Sensitivity analyses were undertaken to assess uncertainty in the model. Results: Use of LB + TT identified actionable alterations in more patients, 68.5 versus 52.7% with TT alone. Use of the LB + TT strategy resulted in an incremental cost savings of $3065 CAD per patient (95% CI, 2195-3945) and a gain in quality-adjusted life-years of 0.02 (95% CI, 0.01-0.02) versus TT alone. More patients received chemo-immunotherapy based on TT with higher overall costs, whereas more patients received targeted therapy based on LB + TT with net cost savings. Major drivers of cost-effectiveness were drug acquisition costs and prevalence of actionable alterations. Conclusion: The addition of LB to TT as initial molecular testing of clinically selected patients with advanced NSCLC did not increase system costs and led to more patients receiving appropriate targeted therapy.

20.
Case Rep Oncol ; 15(1): 285-290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529290

RESUMO

Epidermal growth factor receptor (EGFR) mutations are usually oncogenic drivers of lung tumor development and progression. While common sensitizing mutations respond well to targeted therapy, the relevance of germline EGFR mutations is less clear. We describe a 65-year-old, previously healthy, male diagnosed with non-small-cell lung cancer. Familial history for lung cancer is negative. Targeted next-generation sequencing on the tumor biopsy sample revealed an atypical EGFR K757N mutation at 50% allele frequency and genetic review of a previously acquired gastric sample confirms the mutation as a germline change. He received standard first-line chemoimmunotherapy with carboplatin, pemetrexed, and pembrolizumab, and after 8 months therapy continues, with stable disease, to receive maintenance pemetrexed and pembrolizumab. To our knowledge, this is the first report of an atypical, germline K757N EGFR mutation. While the clinical relevance of this mutation is unclear, standard reporting of the allelic frequency of novel, atypical mutations can detect potential germline changes.

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