448 research outputs found
Lung Cancer: Current Therapies and New Targeted Treatments
No full textSanjay Popat of the Royal Marsden Hospital in London, England, presents a discussion on current therapies and treatments for lung cancer. He focuses on drug therapy, including chemotherapy, molecular targeted therapy, checkpoint inhibitor therapy, and chemo-immunotherapy combination therapy.This presentation was originally given during the SCTS Ionescu University program at the 2019 Annual Meeting of the Society for Cardiothoracic Surgery in Great Britain and Ireland. This content is published with the permission of SCTS. Please click here for more information on SCTS educational programs.</div
Crizotinib-Resistant ROS1 G2101A Mutation Associated With Sensitivity to Lorlatinib in ROS1-Rearranged NSCLC: Case Report
No full textgene rearrangements occur in 1% to 2% of NSCLC. Acquired “on-target” mutations within the ROS1 kinase domain are a known resistance mechanism to the first-line ROS1 inhibitor crizotinib. Here, we report the first case of a patient with an acquired ROS1 G2101A resistance mutation after first-line crizotinib, who responded to lorlatinib. The response was dramatic but short in duration
Severe immune checkpoint inhibitor hepatitis in KRAS G12C-mutant NSCLC potentially triggered by sotorasib: case report
No full textSotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. Here, we report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis. Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity
Highlights in lung cancer in 2019.
No full textThere have been significant advances in the treatment landscape of lung cancer in the recent few years. In this podcast, Jonathan Lim (a member of the European Society for Medical Oncology Young Oncologists Committee) interviews Professor Sanjay Popat (Professor of Thoracic Medical Oncology at The Royal Marsden Hospital, UK) on the highlights of lung cancer in 2019.
Professor Popat provides his perspective and contextualises how some of the key studies reported this year (including CheckMate 227, IMpower110, KEYNOTE 042, FLAURA and CASPIAN) have been practice-changing. We also discuss the current utility and caveats of PD-L1(programmed death-ligand 1) as a biomarker for immunotherapy with anti-PD1, and explore progress made in the clinical translation of circulating tumour DNA, circulating tumour cell and tumour mutational burden. Finally, we talk about the recent hype on targeting KRAS in non-small cell lung cancer, and highlight what is on the horizon in 2020. Click here to listen to the Podcast (https://soundcloud.com/bmjpodcasts/highlights-in-lung-cancer-2019?in=bmjpodcasts/sets/esmo-open)
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Health-related quality of life in the randomized phase III trial of brigatinib vs crizotinib in advanced ALK inhibitor–naive ALK + non−small cell lung cancer (ALTA-1L)
No full text•Brigatinib versus crizotinib delayed time to worsening in GHS/QOL in ALK + NSCLC.•Time to worsening was also delayed in most function and symptoms scores.•Brigatinib improved GHS/QOL and function and symptom scales versus crizotinib.•HRQOL was better with first-line brigatinib vs crizotinib in advanced ALK + NSCLC.
In ALTA-1 L, first-line brigatinib versus crizotinib significantly prolonged progression-free survival in advanced ALK-positive (ALK+) non–small cell lung cancer (NSCLC). We report health-related quality of life (HRQOL) outcomes from ALTA-1 L.
HRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) and lung cancer–specific module (QLQ-LC13). HRQOL time to worsening, change from baseline, and duration of improvement were analyzed.
EORTC QLQ-C30 and QLQ-LC13 compliance was >90 % for both groups (n = 131 each). Brigatinib versus crizotinib significantly delayed time to worsening in the EORTC QLQ-C30 global health status (GHS)/QOL (median: 26.74 vs 8.31 months; hazard ratio [HR]: 0.70; 95 % CI: 0.49, 1.00; log-rank P = 0.0485); emotional functioning, social functioning, fatigue, nausea and vomiting, appetite loss, and constipation scales (log-rank P < 0.05); delays in time to worsening for the physical, role, and cognitive functioning scales were not statistically significant. Mean change from baseline showed greater improvement in GHS/QOL and most EORTC QLQ-C30 functional and symptom scales with brigatinib versus crizotinib. Among patients with GHS/QOL improvement, brigatinib had longer duration of improvement versus crizotinib (median: not reached vs 11.99 months); similar results were seen in the physical, role, emotional, and social functioning; fatigue; nausea and vomiting; and appetite loss scales. Median time to worsening in dyspnea (QLQ-LC13) was 23.98 versus 8.25 months (brigatinib vs crizotinib; HR: 0.64; 95 % CI: 0.39, 1.05).
Brigatinib significantly delayed time to worsening and prolonged duration of improvement in GHS/QOL versus crizotinib, supported by improvement in functional and symptom scores. These preliminary analyses suggest brigatinib is the first ALK inhibitor with better HRQOL versus another ALK inhibitor in ALK inhibitor–naive advanced ALK + NSCLC
Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer
No full textAs advanced non-small cell lung cancer (aNSCLC) is being increasingly divided into rare oncogene-driven subsets, conducting randomised trials becomes challenging. Using real-world data (RWD) to construct control arms for single-arm trials provides an option for comparative data. However, non-randomised treatment comparisons have the potential to be biased and cause concern for decision-makers. Using the example of pralsetinib from a RET fusion-positive aNSCLC single-arm trial (NCT03037385), we demonstrate a relative survival benefit when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts. Quantitative bias analyses show that results for the RWD-trial comparisons are robust to data missingness, potential poorer outcomes in RWD and residual confounding. Overall, the study provides evidence in favour of pralsetinib as a first-line treatment for RET fusion-positive aNSCLC. The quantification of potential bias performed in this study can be used as a template for future studies of this nature
Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2 - Systematic review and meta-analysis.
No full textBackground Immune checkpoint inhibitors (ICIs) are standard of care in advanced non-small cell lung cancer (NSCLC), however their status in patients with poor performance status (PS) is poorly defined. We aimed to evaluate the efficacy and safety of ICIs in NSCLC patients with PS ≥ 2. Methods We conducted a systematic review and meta-analysis of interventional and observational studies, which reported efficacy and safety data on ICIs in PS ≥ 2 comparing to PS ≤ 1 NSCLC patients. Efficacy endpoints included: Objective Response Rate (ORR), Disease-Control Rate (DCR), Overall Survival (OS), Progression-Free Survival (PFS). Safety endpoint was the incidence of severe (grade≥3) Adverse Events (AE). Random-effects model was applied for meta-analysis. Heterogeneity was assessed using I 2 . The review is registered on PROSPERO (CRD42020162668). Findings Sixty-seven studies (n = 26,442 patients) were included. In PS ≥ 2 vs. PS ≤ 1 patients, the pooled odds ratios were: for ORR 0.46 (95 %CI: 0.39-0.54, I 2 :0 %); for DCR 0.39 (95 %CI: 0.33-0.48, I 2 :50 %) and for AEs 1.12 (95 %CI: 0.84-1.48, I 2 :39 %). The pooled hazard ratio for PFS was 2.17 (95 %CI: 1.96-2.39, I 2 :65 %) and for OS was 2.76 (95 %CI: 2.43-3.14, I 2 :76 %). The safety profile was comparable regardless of the PS status. Interpretation Patients with impaired PS status are, on average, twice less likely to achieve a response when exposed to ICIs when compared with representative PS ≤ 1 population. For lung cancer patients treated with ICIs, the impaired PS is not only prognostic, but also predictive for response, while the safety profile is not affected. Prospective randomized studies are indispensable to determine whether poor PS patients derive benefit from ICIs
Association Between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non–Small Cell Lung Cancer
No full textIMPORTANCE: There is a need to tailor treatments to patients who are most likely to derive the greatest benefit from them to improve patient outcomes and enhance cost-effectiveness of cancer therapies. OBJECTIVE: To compare overall survival (OS) between patients with a current or former history of smoking with patients who never smoked and initiated pembrolizumab monotherapy as first-line (1L) treatment for advanced non–small lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study compared patients diagnosed with advanced NSCLC aged 18 or higher selected from a nationwide real-world database originating from more than 280 US cancer clinics. The study inclusion period was from January 1, 2011, to October 1, 2019. EXPOSURES: Smoking status at the time of NSCLC diagnosis. MAIN OUTCOMES AND MEASURES: OS measured from initiation of 1L pembrolizumab monotherapy. RESULTS: In this retrospective cohort study, a total of 1166 patients (median [IQR] age, 72.9 [15.3] years; 581 [49.8%] men and 585 [50.2%] women) were assessed in the primary analysis, including 91 patients [7.8%] with no history of smoking (ie, never-smokers) and 1075 patients [92.2%] who currently or formerly smoked (ie, ever-smokers). Compared with ever-smokers, never-smokers were older (median age [IQR] of 78.2 [12.0] vs 72.7 [15.5] years), more likely to be female (61 [67.0%] vs 524 [48.7%]) and to have been diagnosed with nonsquamous tumor histology (70 [76.9%] vs 738 [68.7%]). After adjustment for baseline covariates, ever-smokers who initiated 1L pembrolizumab had significantly prolonged OS compared to never-smokers (median OS: 12.8 [10.9-14.6] vs 6.5 [3.3-13.8] months; hazard ratio (HR): 0.69 [95% CI, 0.50-0.95]). This trend was observed across all sensitivity analyses for the 1L pembrolizumab cohort, but not for initiators of 1L platinum chemotherapy, for which ever-smokers showed significantly shorter OS compared with never-smokers (HR, 1.2 [95% CI, 1.07-1.33]). CONCLUSIONS AND RELEVANCE: In patients with advanced NSCLC who received 1L pembrolizumab monotherapy in routine clinical practices in the US, patients who reported a current or former history of smoking at the time of diagnosis had consistently longer OS than never-smokers. This finding suggests that in never-smoking advanced NSCLC, 1L pembrolizumab monotherapy may not be the optimal therapy selection, and genomic testing for potential genomically matched therapies should be prioritized over pembrolizumab in never-smokers
Health technology assessments and real-world evidence: tell us what you want, what you really, really want.
No full textImmune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer.
No full textIn this report from the CAPTURE study (NCT03226886), we demonstrate that a third dose of COVID-19 vaccine boosts neutralizing antibody (NAb) and cellular responses in patients with cancer, including those that had undetectable NAb titers (NAbT) following two vaccine doses or for whom NAbT waned. We have noted that one key member of the CAPTURE consortium—Sanjay Popat—was inadvertently not included in the author list. We now include him as a co-author. There are no additional changes to the declaration of interests statement, since Dr. Popat declares no competing conflict of interest. This author list change is now reflected in the online version of this letter
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