Search

Background: Capmatinib has previously shown activity in treatment-naive and previously treated patients with non-small-cell lung cancer (NSCLC) and a MET exon 14-skipping mutation (METex14). Here, we report the final outcomes from the phase 2 GEOMETRY mono-1 study with an aim to provide further evidence for the activity of capmatinib., Methods: In this non-randomised, multi-cohort, open-label, phase 2 trial conducted in 152 centres and hospitals in 25 countries, with patients treated in 95 centres in 20 countries, eligible patients (aged ≥18 years) with MET-dysregulated, EGFR wild-type, and ALK rearrangement-negative advanced NSCLC (stage IIIB/IV) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were assigned to cohorts (1a, 1b, 2, 3, 4, 5a, 5b, 6 and 7) based on their MET status (METex14 or MET amplification) and previous therapy lines. Patients received capmatinib (400 mg orally twice daily) in 21-day treatment cycles. The primary endpoint was overall response rate by blinded independent central review per Response Evaluation Criteria in Solid Tumours version 1.1 and was performed on the full analysis set (all patients who received at least one dose of capmatinib). Previous reports of this study had published interim or primary data for cohorts 1-7. Here, we report the final clinical outcomes from all METex14 cohorts (4, 5b, 6, and 7) and safety from all study cohorts (1-7). The trial is registered with ClinicalTrials.gov, NCT02414139, and has been completed., Findings: Of 373 treated patients enrolled from June 11, 2015, to March 12, 2020, 160 (97 [61%] female) patients had METex14 NSCLC and were enrolled in four cohorts: 60 treatment-naive (cohorts 5b and 7) and 100 previously treated (cohorts 4 and 6). The overall median study follow-up was 46·4 months (IQR 41·8-65·4) for the treatment-naïve patients and 66·9 months (56·7-73·9) for previously treated patients, respectively. Overall responses were recorded in 41 (68%; 95% CI 55·0-79·7) of 60 treatment-naive patients and 44 (44%; 95% CI 34·1-54·3) of 100 previously treated patients. In all 373 treated patients, the most common treatment-related adverse events were peripheral oedema (n=174; 47%), nausea (n=130; 35%), increased blood creatinine (n=78; 21%), and vomiting (n=74; 20%). Grade 3-4 serious adverse events occurred in 164 (44%) patients, dyspnoea being the most common (18 patients [5%]). Treatment-related deaths occurred in four (1%) patients (one each of cardiac arrest, hepatitis, organising pneumonia, and pneumonitis). No new safety signals were reported., Interpretation: These long-term results support METex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with METex14 NSCLC., Funding: Novartis Pharmaceuticals., Competing Interests: Declaration of interests JW reports research grant support (to their institution) from Bristol Myers Squibb, Janssen Pharmaceutica, Novartis, and Pfizer; and consulting fees or honoraria for lectures and for attending meetings from Amgen, AstraZeneca, Bayer, Blueprint, Bristol Myers Squibb, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Janssen, Lilly, Loxo, Merck, Mirati, MSD, Novartis, Nuvalent, Pfizer, Pierre Fabre, Roche, Seattle Genetics, Takeda, and Turning Point. MH declares personal honoraria for lectures and presentations from Boehringer Ingelheim, AstraZeneca, Takeda, Amgen, MSD, and Roche. J-YH reports research grants from Pfizer, Takeda, and ONO; consulting fees or honoraria for lectures and presentations from AstraZeneca, Jassen, Amgen, Oncobix, Daiichi Sankyo, Merck, Norvatis, Abion, Takeda, Pfizer, and Yuhan; participation in data safety monitoring board for AstraZeneca, Jassen; and a leadership role for National Cancer Drug Assessment Committee. NR declares research grants from Artidis, MSD, Amgen, and Roche; honoraria for lectures and presentations from Amgen, AstraZeneca, Bristol Myers Squibb, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi, Takeda, and Regeneron; support for attending the meetings from Takeda, Regeneron, and Roche; and participation in a data safety monitoring and advisory board for AbbVie, Amgen, AstraZeneca, Bayer, Boehringer, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi, Takeda, and Regeneron. P-JS reports the research grants received (to their institution) from AstraZeneca, Bristol Myers Squibb, Genentech, and Gilead; and consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, Pfizer, and Takeda. EFS reports consulting fees support to their institution from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen, MSD, Roche, Sanofi, Takeda, and Merck; honoraria for lectures and presentations for self from Boehringer Ingelheim and Daiichi Sankyo; and participation in a data safety monitoring and advisory board for Daiichi Sankyo and Taiho for institution. JV declares consulting fees received from Bristol Myers Squibb, Janssen, and PDCline; honoraria for lectures and presentations from AstraZeneca, Daiichi Sankyo, and Merck; and participation in a data safety monitoring and advisory board for AstraZeneca, Boehringer, and Transgene. MN reports honoraria received for lectures and presentations from Ono Pharmaceuticals, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Lilly, AstraZeneca, MSD, AbbVie, Takeda Pfizer, Boehringer, Ingelheim, Novartis, Nippon, Kayaku, Merck, and Janssen; and support for attending meetings from Novartis. WA declares research grants received from Bristol Myers Squibb, AstraZeneca, Bioatla, Imugene, Astride, BridgeBio, AbbVie, and Novocure; and participation in data safety monitoring and advisory board for Lilly. EBG reports research grants received (to their institution) from ABL-Bio, Arrivent, AstraZeneca, Bristol Myers Squibb, Daiichi, Sanko, Eli Lilly, EMD Serono, Genentech, Gilead, Iovance Biotherapeutics, Merck, Prelude, Regeneron, and Synthekine; consulting fees from AbbVie, Arcus, AstraZeneca, Arrivent, Atreca, BridgeBio, Bristol Myers Squibb, EMD Serono, Eli Lilly, Gilead, GlaxoSmithKline, Hookipa, LianBio, Merckl Merus, Novartis, Nuvalent, Personalis, Regeneron, Sanofi, Seagan, Sensei, Sumitomo, Strata, Summit, Synthekine, Xilio, and Zymeworks; support for attending meetings from A2 and Novartis; patents issued (to their institution); and other financial support for independent medical education from Daiichi Sankyo and Ipsen. DSWT reports research grants support to their institution from ACM Biolabs, Amgen, AstraZeneca, Bayer, and Pfizer, outside of the submitted work; consulting fees from Amgen, AstraZeneca, Bayer, Boehringer, Ingelheim, DKSH, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, and Takeda; honoraria for lectures and presentations from Amgen, Bayer, Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda, BeiGene, Regeneron, and Zymeworks; and support for attending meetings from Bayer, Merck, Pfizer, Regeneron, and Zymeworks. TS declares honoraria for lectures from Amgen, AnHeart Therapeutics, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, GlaxoSmithKline, MSD, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Takeda Pharmaceutical, and Towa Pharmaceutical. GMF declares the stocks and shareholder for Roche. AR, MC, SLM, CB, YY, LJ, LF, and AY are employees of Novartis. AB reports stocks and stock options from Novartis and Daiichi Sankyo. RSH declares research grants received to their institution for clinical trials from AbbVie, Agios, Corvus, Daichii Sankyo, Erasca, Lilly, Mirati, Mythic, Novartis, and Turning Point; and consulting fees for self from AbbVie, Astrazeneca, Biohaven, Claim Therapeutics, Daichii Sankyo, EMD Serono, Lilly, Merck, Novartis, Regeneron, and Sanofi. SVO, HJMG, and MJ declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Neoantigen immunoediting drives immune checkpoint blockade efficacy, yet the molecular features of neoantigens and how neoantigen immunogenicity shapes treatment response remain poorly understood. To address these questions, 80 patients with non-small cell lung cancer were enrolled in the biomarker cohort of CheckMate 153 (CA209-153), which collected radiographic guided biopsy samples before treatment and during treatment with nivolumab. Early loss of mutations and neoantigens during therapy are both associated with clinical benefit. We examined 1,453 candidate neoantigens, including many of which that had reduced cancer cell fraction after treatment with nivolumab, and identified 196 neopeptides that were recognized by T cells. Mapping these neoantigens to clonal dynamics, evolutionary trajectories and clinical response revealed a strong selection against immunogenic neoantigen-harboring clones. We identified position-specific amino acid and physiochemical features related to immunogenicity and developed an immunogenicity score. Nivolumab-induced microenvironmental evolution in non-small cell lung cancer shared some similarities with melanoma, yet critical differences were apparent. This study provides unprecedented molecular portraits of neoantigen landscapes underlying nivolumab's mechanism of action., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Cell cycle inhibition is an established therapeutic approach for some cancers. A multicenter, single-arm, phase 2 trial (ClinicalTrials.gov identifier NCT00937937) of the cyclin-dependent kinase inhibitor SCH 727965 (NSC 747135; dinaciclib) was conducted in patients with metastatic melanoma to determine its clinical activity., Methods: Patients with metastatic melanoma of cutaneous or mucosal origin were eligible if they had zero to one previous treatments, a Zubrod performance status of 0-1, and adequate organ function. SCH 727965 50 mg/m 2 was given intravenously every 3 weeks until progression. Co-primary end points were 1-year overall survival (OS) and 6-month progression-free survival (PFS)., Results: Seventy-two patients were enrolled from July 1, 2009, to November 1, 2010, at 24 institutions. Sixty-eight percent of patients had M1c disease, and 43% had elevated lactate dehydrogenase levels. Twenty-eight patients (39%) experienced grade 4 adverse events, including 20 cases of neutropenia. Sixty-seven patients were evaluable for response. There was a response in zero of 67 patients (95% confidence interval [CI], 0%-5%), and stable disease was observed in 21%. The estimated median PFS was 1.4 months (95% CI, 1.4-1.5 months), and the 6-month PFS rate was 6% (2%-13%). The median OS was 8.2 months (95% CI, 5.5-10.5 months), and the 1-year OS rate was 38% (95% CI, 26%-49%)., Conclusions: This multicenter, US National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial of SCH 727965 was conducted at a time when the current generation of effective therapies for melanoma were not available. Although the null hypothesis of 1-year OS was rejected, the minimal PFS impact and substantive toxicity indicated that this regimen lacks justification for further investigation as a single agent., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations., Methods: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment., Results: Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm 3 , p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067)., Conclusion: The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

Observational data (e.g. electronic health records) has become increasingly important in evidence-based research on dynamic treatment regimes, which tailor treatments over time to patients based on their characteristics and evolving clinical history. It is of great interest for clinicians and statisticians to identify an optimal dynamic treatment regime that can produce the best expected clinical outcome for each individual and thus maximize the treatment benefit over the population. Observational data impose various challenges for using statistical tools to estimate optimal dynamic treatment regimes. Notably, the task becomes more sophisticated when the clinical outcome of primary interest is time-to-event. Here, we propose a matching-based machine learning method to identify the optimal dynamic treatment regime with time-to-event outcomes subject to right-censoring using electronic health record data. In contrast to the established inverse probability weighting-based dynamic treatment regime methods, our proposed approach provides better protection against model misspecification and extreme weights in the context of treatment sequences, effectively addressing a prevalent challenge in the longitudinal analysis of electronic health record data. In simulations, the proposed method demonstrates robust performance across a range of scenarios. In addition, we illustrate the method with an application to estimate optimal dynamic treatment regimes for patients with advanced non-small cell lung cancer using a real-world, nationwide electronic health record database from Flatiron Health., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along with safety, pharmacokinetics, and biomarker assessments. Of 235 patients, 142 were naive to anti-PD-1/L1 and 93 were pretreated with anti-PD-1/L1 antibodies. Durable responses (>24 months) were seen across all indications for patients naive to anti-PD-1/L1 and in melanoma and RCC patients pretreated with anti-PD1/L1. The most frequent study drug-related AEs were pruritus (15.5%), fatigue (10.6%), and rash (10.6%) in patients naive to anti-PD-1/L1 and fatigue (18.3%), rash (14.0%), and nausea (10.8%) in anti-PD-1/L1 pretreated patients. Biomarker assessment indicated higher expression of T-cell-inflamed gene signature at baseline among responding patients. Response to treatment was durable (>24 months) in some patients across all enrolled indications, and safety findings were in accordance with previous and current studies exploring LAG-3/PD-1 blockade., Competing Interests: CCL reports consulting fees from AbbVie, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Daiichi-Sankyo, Merck KGaA, Novartis, PharmaEngine; payment or honoraria from Eli Lilly, Novartis, and Roche; and support for attending meetings or travel from BeiGene, Daiichi-Sankyo, and Eli Lilly. EG reports grants or contracts from Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho, and BeiGene; payment or honoraria from Roche, Genentech, F. Hoffmann-La Roche, Ellipses Pharma, Neomed Therapeutics Inc, Boehringer Ingelheim, Janssen Global Services, SeaGen, Alkermes, Thermo Fisher, BMS, MabDicovery, Anaveon, F-Star Therapeutics, Hengrui; participated on data safety monitoring board or advisory board for Roche, Genentech, Boehringer Ingelheim, Janssen Global Services, Thermo Fisher, Anaveon, MabDiscovery, Novartis and Lilly; and serves as PI or Co-PI for Affimed Gmbh. Amgen SA, Anaveon AG, AstraZeneca AB, Biontech Gmbh, Catalym Gmbh, Cytomx, F. Hoffmann-La Roche Ltd, F-Star Beta Limited, Genentech Inc, Genmab B.V, Hutchison Medipharma Limited, Icon, Imcheck Therapeutics, Immunocore Ltd, Janssen-Cilag SA, Medimmune Llc, Merck KGaA, Novartis Farmacéutica SA, Peptomyc, Ribon Therapeutics, Roche Farma SA, Seattle Genetics Inc, Symphogen A/S, Taiho Pharma Usa Inc PS reports grants or contracts from CoBioRes NV, Eisai, G1 Therapeutics, PharmaMar, Genmab, Merck, Sartar Therapeutics, ONA therapeutics; honoraria from Blueprint Medicines; and consulting fees from Deciphera, Ellipses Pharma, Blueprint Medicines, Transgene, Exelixis, Boehringer Ingelheim, Studiecentrum voor Kernenergie, SQZ biotechnology, CRT Pioneer Fund LP, Adcendo, PharmaMar, Merck Healthcare KGaA, Ysios Capital. DSH reports grants or contracts from AbbVie, Adaptimmune, Aldi-Norte, Amgen, AstraZeneca, Bayer, BMS, Daiichi-Sankyo, Deciphera, Eisai, Erasca, Fate Therapeutics, Genentech, Genmab, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, Medimmune, Mirati, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, SeaGen, Takeda, Turning Point Therapeutics, Verstatem, and VM Oncology; travel, accommodation, expenses from Bayer, Genmab, and Telperian; consulting fee from Adaptimmune, Alpha Insights, Acuta, Alkermes, Amgen, Aumbiosciences, Atheneum, Axiom, Barclays, Baxter, Bayer, Boxer Capital, BridgeBio, CDR-life AG, COR2ed, COG, Ecor1, Genentech, Gilead, GLG, Group H, Guidepoint, HCW Precision, Immunogen, Infinity, Janssen, Liberium, Medscape, Numab, Oncologia Brasil, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, Seattle Genetics, ST Cube, Takeda, Tavistock, Trieza Therapeutics, Turning Point, WebMD, and Ziopharm; and other ownership interests for OncoResponse (founder) and Telperian Inc (advisor). LLS reports stock ownership or equity in Agios (spouse); leadership in Treadwell Therapeutics (spouse is co-founder); and consulting fee/advisory board for Merck, Pfizer, AstraZeneca, Roche, Symphogen, GSK, Voronoi, Treadwell Therapeutics, Arvinas, Tessa, Navire, Relay, Rubius, Janpix, Daiichi-Sankyo, Coherus, Amgen, and Marengo; grant/research support (clinical trials for institution) for Novartis, BMS, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca/Medimmune, Merck, Celgene, Astellas, Bayer, AbbVie, Amgen, Symphogen, Intensity Therapeutics, Mirati, Shattucks, and Avid. MigM reports honoraria from SeaGen, Lilly, AstraZeneca, Pfizer, Daiichi-Sankyo, Roche; consulting fees from Roche, Novartis, AstraZeneca, Daiichi-Sankyo, SeaGen, Lilly, Sanofi; advisory board of Novartis and holds leadership roles in GEICAM (Board of Directors), TRIO. RH reports grants and contacts for clinical trials for institution from AstraZeneca, BMS, Corvus, Eli Lilly, MSD, Novartis, Olema, Oncosec, Roche, SeaGen; honoraria from AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer, Roche; participates in advisory board of AstraZeneca, BMS, Eisai, Eli Lilly, Merck, MSD, Novartis, OncoSec, Pfizer, Roche, SeaGen. RAS reports grants from AstraZeneca and Boehringer Ingelheim, and personal fees from AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan, Amgen, Bayer, Puma. TZ reports grants from Genentech Roche, OmniSeq, SeaGen, PGDx, Janssen, AstraZeneca, Pfizer, AbbVie/StemcentrX, Merck, Regeneron, Mirati Therapeutics, Novartis, Merrimack; consulting fees from Genentech Roche, Eli Lilly, Bayer, QED Therapeutics, Eisai, Calithera, Aveo Pharmaceuticals, Amgen, BMS, Dendreaon, Sanofi-Aventis, Janssen, AstraZeneca, Pfizer, Merck, Exelixis; honoraria from MJH Associates, Aptitude Health, PlatformQ, Integrity CE, Vaniam Group, PeerView, and Novartis; travel support from SUO, Kidney Cancer Association, and KCCure; and leadership role in NCI GU Steering Renal Task force, KCA Medical Steering committee, and KCCure Scientific advisory board. BM reports grant from Health and Medical Research Fund, Merck Serono, Boehringer Ingelheim Inc; consulting fees from Viracta therapeutics and Y-Biologics; honoraria from MSD, Novartis, Merck, Y-Biologics, Springer, Elsevier, Daiichi, Taiho, and Pierra Fabre; holds leadership roles in ethics committee of NTEC-CUHK, ESMO Asia 2020 and ESMO 2022 (Track Chair – Paris, Singapore), ASCO 2020 (Session chair), and ESMO Asia 2019 (Co-Chair). CK reports research funding from BMS, Merus, and Gritstone Oncology. DT reports honoraria and consulting/advisory roles for Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, and Takeda; consulting/advisory roles for Bayer, AstraZeneca, Eli Lilly, and GlaxoSmithKline; and research funding for Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer, and Amgen. PAC reports research funding from AbbVie, Adlai Nortye, Alligator, Amgen, AstraZeneca, Blueprint Medicines, Boston, Bristol Myers Squibb, Celgene, Debio Pharm, Dragonfly, Exelixis, GlaxoSmithKline, Innate Pharma, Janssen, Eli Lilly, Loxo, Molecular Partners, MSD, Novartis, OSE Pharma, Relay, Roche/Genentech, Sotio, Taiho Pharmaceutical, Toray Industries, Transgene, and Turning Point Therapeutics; personal fees from AstraZeneca, Amgen, Merck Serono, Novartis, and Roche/Genentech; nonfinancial research support from AstraZeneca, Debio Pharm, MSD, Novartis, Plexxikon, and Roche/Genentech; and travel accommodation from BMS, MSD, and NETRIS Pharma. JS reports consulting/advisory roles for Astellas Pharma, AstraZeneca/MedImmune, Bayer, Eisai, Roche/Genentech, Pfizer, Immunocore, SeaGen, Novartis, Sun Pharma, EMD Serono, Amgen, Bristol-Myer Squib, Flugent Therapeutics, Exelixis, Merck, Takeda, and Array BioPharma. AW received research grants from Merck and BMS; consulting fees from Ipsen, Astella, BMS; and honoraria from Ipsen, Pfizer, BMS. RDC received research funding from Amgen, Astellis, AstraZeneca, BMS, Corvus, Ideaya, Immunocore, Iovance, Merck, Mirati, Novartis, Pfizer, Plexxikon, Regeneron, Roche/Genentech; consulting fees from Alkermes, BMS, Castle Biosciences, Eisai, Ideaya, Immunocore, InxMed, Iovance, Merck, Novartis, Oncosec, Pierre Fabre, PureTech Health, Regeneron, Sanofi Genzyme, Sorrento Therapeutics, Trisalus; participated in data safety monitoring or advisory board of Aura Biosciences, Chimeron, and Rgenix; and stocks in Aura Biosciences, Chimeron, and Rgenix. TE reports grants for MSD, Novartis, Dainipon Sumitomo, Ono, Daiichi-Sankyo, Astellas, Astellas Amgen Biopharma, Parexel, Chugai, Quintiles, Syneos Health, Pfizer, IQVIA; and honoraria from MSD, Ono, Daiichi-Sankyo, Eli Lilly, Taiho, Chugai, and Sanofi. FR reports consulting fees from BMS and MSD; honoraria from Merck KGaA. FDB reports consulting fees from NMS Nerviano, Menarini, AstraZeneca, Incyte; honoraria from BMS, Merck Group, MDS, Pfizer, Servier, Sanofi, Roche, Amgen, Incyte; travel support from Roche; and participated in advisory board of Pierre Fabre, AstraZeneca, MSD Serono, BMS, Roche, Sanofi, Novartis. LR is employee of Novartis. MicM, JC, JS, WA, BDB reports no conflicts of interest. TS, NRC, DG, EK and VA were employees of Novartis at the time of study conduct. EK and VA report stocks from Novartis., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Leptomeningeal disease (LMD) is a devastating complication for patients with advanced cancer. Diagnosis and monitoring the response to therapy remains challenging due to limited sensitivity and specificity of standard-of-care (SOC) diagnostic modalities, including cerebrospinal fluid (CSF) cytology, MRI, and clinical evaluation. These hindrances contribute to the poor survival of LMD patients. CNSide is a CLIA-validated test that detects and characterizes CSF-derived tumor cells and cell-free (cf) DNA. We performed a retrospective analysis on the utility of CNSide to analyze CSF obtained from advanced non-small cell lung cancer (aNSCLC) patients with suspected LMD treated at the Huntsman Cancer Institute in Salt Lake City, UT., Methods: CNSide was used to evaluate CSF from 15 patients with aNSCLC. CSF tumor cell quantification was performed throughout treatment for 5 patients. CSF tumor cells and cfDNA were characterized for actionable mutations., Results: In LMD-positive patients, CNSide detected CSF tumor cells in 88% (22/25) samples versus 40% (10/25) for cytology (matched samples). CSF tumor cell numbers tracked response to therapy in 5 patients where CNSide was used to quantify tumor cells throughout treatment. In 75% (9/12) of the patients, genetic alterations were detected in CSF, with the majority representing gene mutations and amplifications with therapeutic potential. The median survival for LMD patients was 16.1 m (5.2-NR)., Conclusions: We show that CNSide can supplement the management of LMD in conjunction with SOC methods for the diagnosis, monitoring response to therapy, and identifying actionable mutations unique to the CSF in patients with LMD., Competing Interests: S.P.: Advisory Board/ Consulting: G1 therapeutics, Jazz Pharma, Pfizer. Research support (to institution): Novocure. A.C.: Advisory Board/ Consulting: Boehringer Ingelheim, Diachi Sankyo, Adpatimmune. Research funding (to the institution): GlaxoSmithKline, BioAtla, Tracon, Boehringer Ingelheim. S.B.P.: Speakers Bureau: Astra Zeneca, Regeneron, Merck. Research Funding (to institution): Janseen, AstraZeneca. B.B. is an employee of Biocept and holds stocks in the company. W.A.: Data Safety Monitoring for Eli Lilly, Research Funding (to institution) BMS and AstraZeneca. R.M., K.K., K.M., and L.C.: No conflicts of interest, (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell survival, leading to immunogenic cell death and enhanced antitumour immune response. In preclinical models of non-small-cell lung cancer, TTFields amplified the effects of chemotherapy and immune checkpoint inhibitors. We report primary results from a pivotal study of TTFields therapy in metastatic non-small-cell lung cancer., Methods: This randomised, open-label, pivotal phase 3 study recruited patients at 130 sites in 19 countries. Participants were aged 22 years or older with metastatic non-small-cell lung cancer progressing on or after platinum-based therapy, with squamous or non-squamous histology and ECOG performance status of 2 or less. Previous platinum-based therapy was required, but no restriction was placed on the number or type of previous lines of systemic therapy. Participants were randomly assigned (1:1) to TTFields therapy and standard systemic therapy (investigator's choice of immune checkpoint inhibitor [nivolumab, pembrolizumab, or atezolizumab] or docetaxel) or standard therapy alone. Randomisation was performed centrally using variable blocked randomisation and an interactive voice-web response system, and was stratified by tumour histology, treatment, and region. Systemic therapies were dosed according to local practice guidelines. TTFields therapy (150 kHz) was delivered continuously to the thoracic region with the recommendation to achieve an average of at least 18 h/day device usage. The primary endpoint was overall survival in the intention-to-treat population. The safety population included all patients who received any study therapy and were analysed according to the actual treatment received. The study is registered with ClinicalTrials.gov, NCT02973789., Findings: Between Feb 13, 2017, and Nov 19, 2021, 276 patients were enrolled and randomly assigned to receive TTFields therapy with standard therapy (n=137) or standard therapy alone (n=139). The median age was 64 years (IQR 59-70), 178 (64%) were male and 98 (36%) were female, 156 (57%) had non-squamous non-small-cell lung cancer, and 87 (32%) had received a previous immune checkpoint inhibitor. Median follow-up was 10·6 months (IQR 6·1-33·7) for patients receiving TTFields therapy with standard therapy, and 9·5 months (0·1-32·1) for patients receiving standard therapy. Overall survival was significantly longer with TTFields therapy and standard therapy than with standard therapy alone (median 13·2 months [95% CI 10·3-15·5] vs 9·9 months [8·1-11·5]; hazard ratio [HR] 0·74 [95% CI 0·56-0·98]; p=0·035). In the safety population (n=267), serious adverse events of any cause were reported in 70 (53%) of 133 patients receiving TTFields therapy plus standard therapy and 51 (38%) of 134 patients receiving standard therapy alone. The most frequent grade 3-4 adverse events were leukopenia (37 [14%] of 267), pneumonia (28 [10%]), and anaemia (21 [8%]). TTFields therapy-related adverse events were reported in 95 (71%) of 133 patients; these were mostly (81 [85%]) grade 1-2 skin and subcutaneous tissue disorders. There were three deaths related to standard therapy (two due to infections and one due to pulmonary haemorrhage) and no deaths related to TTFields therapy., Interpretation: TTFields therapy added to standard therapy significantly improved overall survival compared with standard therapy alone in metastatic non-small-cell lung cancer after progression on platinum-based therapy without exacerbating systemic toxicities. These data suggest that TTFields therapy is efficacious in metastatic non-small-cell lung cancer and should be considered as a treatment option to manage the disease in this setting., Funding: Novocure., Competing Interests: Declaration of interests TL reports support towards this manuscript from Novocure; institutional grants or contracts from Advaxis and Pfizer; consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Blueprint, Daiichi-Sankyo, Eisai, Eli Lilly, EMD Serono, Genentech, Janssen, Jazz Pharmaceuticals, Merck, Mirati, Novocure, Regeneron, Roche, and Takeda; honoraria from Aptitude Health, ASTRO, Bioascend, Cardinal Health, Curio, GRACE, I3 Health, IDEO, Larvol, Medscape, Peerview Institute for Medical Education, OncLive, Opinions in Lung Cancer, Society for Immunotherapy of Cancer, Targeted Oncology, UpToDate, and Vindico; and board participation or a leadership position for the National Cancer Institute and Georgia Society of Clinical Oncology. RK reports institutional grants or contracts from AstraZeneca, Blue Earth Diagnostics, Brainlab, Cantex Pharmaceuticals, Exelixis, GT Medical Technologies, Medtronic, Novocure, and ViewRay; consulting fees from Castle Biosciences, Elekta, Kazia Therapeutics, and ViewRay; honoraria from Accuray, Brainlab, Elekta, Elsevier, Novocure, Peerview Institute for Medical Education, and ViewRay; support for travel or meeting attendance from Accuray, Elekta, Novocure, and the Peerview Institute for Medical Education; and participation on an advisory board for ViewRay. RR reports consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Merck, MSD, Parexel, Pfizer, Roche, and Takeda; advising or speaking fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, MSD, Novartis, Parexel, Pfizer, and Roche; support for meetings or travel from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, MSD, Novartis, Parexel, Pfizer, Roche, and Takeda; and participation on an advisory board for Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Parexel, Pfizer, Roche, and Takeda. LZ reports participation on a data safety monitoring board or advisory board for AstraZeneca and BeiGene. SK reports honoraria as a speaker for AstraZeneca, Bayer, G1 Therapeutics, Genentech, and Pfizer. JW reports institutional grants from the American Cancer Society, American Lung Association, AstraZeneca, Central Society for Clinical and Translational Research, Gateway for Cancer Research, National Institutes of Health, and Siteman Cancer Center; consulting fees from Novoure and Takeda; honoraria from Washington University Continuing Medical Education and OncLive; support for travel or meeting attendance from Neon Therapuetics; and participation on a data safety monitoring or advisory board for Washington University. TB reports consultancy fees from InhaTarget; participation on a safety monitoring board or advisory board for Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Merck, and Roche; support for travel or meeting attendance from Takeda. DEG reports institutional grants from AstraZeneca, BerGenBio, Karyoparhm, and Novocure; consulting fees from Catalyst Pharmaceuticals; participation on a data safety monitoring or advisory board for BeiGene, Daiichi-Sankyo, Elevation Oncology, Janssen, Mirati, Regeneron, and Sanofi; stock or stock options with Gilead, Medtronic, and Walgreens; and a financial interest in OncoSeer Diagnostics. GK reports honoraria as a speaker or advisory board member from Amgen, AstraZeneca, Bristol-Myers Squibb, EMD Serono, Genentech, Merck, Novartis, and Regeneron; royalties from McGraw Hill; and consulting fees from Primum. RP reports institutional funding from the National Cancer Institute, and a leadership position and travel support from the National Community Oncology Dispensing Association. JA reports honoraria from AstraZeneca, Eli Lilly, and MSD; participation on a data safety monitoring or advisory board for Amphera, AstraZeneca, Bristol-Myers Squibb, MSD, and Takeda; stock or stock options with Amphera; and a leadership role with The International Association for the Study of Lung Cancer (IASLC). AD reports honoraria from Bristol-Myers Squibb; support for meeting attendance or travel from MSD and Roche; and participation on a data safety or advisory board for Novartis, Sanofi, and Takeda. MP reports consulting fees from Abbvie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eisei, Merck, MSD, Novartis, Pfizer, Roche, and Takeda; honoraria from Amgen, Bayer, Janssen, Nestle, and Sanofi; and support for meeting attendance or travel from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Roche, Takeda, and Vifor. RG reports consulting fees, honoraria, participation on a safety monitoring board or advisory board, or support for attending meetings or travel from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Gilead, Janssen, Merck, MSD, Novartis, Roche, Takeda, Sandoz, and Sanofi; and stock or stock options for Eli Lilly and Novo Nordisk. CR reports institutional funding from Pfizer and U54; consulting fees from Archer, Bayer, Boston Pharm, CEA, Daiichi Sankyo, EMD Serono, Eisai, General Dynamics, Genzyme, Inivata, Janssen, Medstar, Mirati, Novartis, Regeneron, and Sanofi; honoraria from AstraZeneca, COR2ED, Intellisphere, MSD, Physicians’ Education Resource, and Roche; and leadership roles with the European Society for Medical Oncology, Elsevier, the European School of Oncology, the International Society of Liquid Biopsy, and the IASLC. WA reports institutional grants from AstraZeneca and Bristol-Myers Squibb. CL reports research funding from AstraZeneca, Eli Lilly, Fujifilm, Janssen Pharmaceuticals, Inovio, Merck, Oncocyte, Takeda, and Trizell, consulting fees from AstraZeneca, Boehringer lngelheim, Genentech/Roche, Gilead, GSK, Merck, Mirati, Novocure, Pfizer, Regeneron, Sanofi-Aventis, and Takeda; participation on a safety monitoring board or advisory board for Amgen, OncocyteDX, the Radiation Therapy Oncology Group Foundation, and the Veterans Administration; and received medical writing support from Novartis. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

A unique approach with rare resources was used to identify candidate variants predisposing to familial nonsquamous nonsmall-cell lung cancers (NSNSCLC). We analyzed sequence data from NSNSCLC-affected cousin pairs belonging to high-risk lung cancer pedigrees identified in a genealogy of Utah linked to statewide cancer records to identify rare, shared candidate predisposition variants. Variants were tested for association with lung cancer risk in UK Biobank. Evidence for linkage with lung cancer was also reviewed in families from the Genetic Epidemiology of Lung Cancer Consortium. Protein prediction modeling compared the mutation with reference. We sequenced NSNSCLC-affected cousin pairs from eight high-risk lung cancer pedigrees and identified 66 rare candidate variants shared in the cousin pairs. One variant in the FGF5 gene also showed significant association with lung cancer in UKBiobank. This variant was observed in 3/163 additional sampled Utah lung cancer cases, 2 of whom were related in another independent pedigree. Modeling of the predicted protein predicted a second binding site for SO 4 that may indicate binding differences. This unique study identified multiple candidate predisposition variants for NSNSCLC, including a rare variant in FGF5 that was significantly associated with lung cancer risk and that segregated with lung cancer in the two pedigrees in which it was observed. FGF5 is an oncogenic factor in several human cancers, and the mutation found here (W81C) changes the binding ability of heparan sulfate to FGF5, which might lead to its deregulation. These results support FGF5 as a potential NSNSCLC predisposition gene and present additional candidate predisposition variants., (© 2023 UICC.)

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Introduction: Currently, there are no publicly-available estimates of indoor radon concentration at scales smaller than the county. Radon-hazard potential soil maps that reflect underlying geologic factors can be created at small geographic scale and linked to residential and census data. We determined the association between residential radon tests and high radon-hazard potential soil at the residential and block group levels using a large Utah-based dataset. We also identified characteristics of block groups with limited tests in the dataset., Methods: We geocoded a dataset of residential radon tests obtained from 2001 to 2017 by a statewide educational program. We linked each location to maps of radon-hazard potential soil, the Environmental Protection Agency's (EPA) county radon zones. We also calculated the number of tests conducted in each block group and linked block groups to demographic data from the 2020 United States census. Log-linear and logistic models identified the association between residential home test results and 1) radon-hazard potential soil of each residence, 2) percent of residences on high radon-hazard potential soils in block groups, and 3) EPA's radon zones. We compared demographic characteristics among block groups with ≥5 or <5 residential tests in our dataset., Results: Approximately 42% of homes in the dataset tested ≥4 pCi/L. We found significant positive associations for residential radon test results with 1) residential location on high radon-hazard potential soil and 2) block groups with >0% of residences on high radon-hazard potential soil. EPA radon zones were not associated with residential test results. Block groups with <5 tests had higher than the statewide median percentage of Hispanic residents (OR = 2.46, 95% CI = 1.89-3.21) and were located in rural counties., Discussion: Radon-hazard potential soil has a significant association with residential home radon tests. More efforts are needed to improve radon testing in block groups that are rural and have greater percentages of racial minorities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Limited-stage small-cell lung cancer (LS-SCLC) is potentially curable with concurrent chemoradiation (CRT). Cisplatin is the preferred platinum for the chemotherapy backbone in national guidelines. Unfortunately, many LS-SCLC patients are elderly, with comorbidities and poor performance status (PS), which preclude the use of cisplatin. Carboplatin may be a suitable alternative. This analysis evaluates the overall survival (OS) and time to next treatment (TTNT) in LS-SCLC patients receiving concurrent CRT by platinum use., Materials and Methods: The study included LS-SCLC patients in the Flatiron Health nationwide de-identified electronic health record-derived database who received CRT in 2013-2019 with follow-up through May 2020. TTNT and OS were compared using both unadjusted and inverse propensity-weighted Cox proportional hazards models., Results: This study included patients treated with carboplatin (n = 600) or cisplatin (n = 572) in combination with etoposide and radiation. Cisplatin patients were younger, had a shorter time from diagnosis to radiation, and had less kidney disease. In an unadjusted analysis, median overall survival (mOS) was greater in the cisplatin group than the carboplatin group with mOS of 22.3 months vs. 19.2 months and Hazard Ratio (HR) of 0.83 (p = 0.01). In the inverse propensity-weighted analysis, this difference was no longer significant (HR 0.93, p = 0.37). No differences were seen in TTNT., Conclusion: When balancing on key clinical factors, we observed no statistical difference in OS or TTNT by platinum choice in real-world LS-SCLC patients treated with CRT.  Although observational, the results from this large data set are consistent with the hypothesis that either cisplatin or carboplatin is an appropriate therapy regardless of health status., Competing Interests: Declaration of Competing Interest Dr. Haaland served as a consultant for Guidepoint Global, Value Analytics Labs, National Kidney Foundation, and Proxima Clinical Research. Dr. Puri reports receiving consulting/advisory fees from AstraZeneca, G1 therapeutics and Jazz Pharma and also reports travel funding from Dava Oncology. Dr. Patel reports receiving institutional funding from Takeda, Merck, AstraZeneca, Janssen; and consulting fees/advisory board fees from AstraZeneca, Natera, Boehringer Ingelheim, Blueprint Medicines, TerSera Therapeutics, Takeda, Regeneron, and Sanofi. Dr. Akerley reports participation on data safety/ advisory board for Lilly. Jennifer Sinnott reports an NIH funding grant. The remaining authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There are few data on the quality of cancer treatment information available on social media. Here, we quantify the accuracy of cancer treatment information on social media and its potential for harm. Two cancer experts reviewed 50 of the most popular social media articles on each of the 4 most common cancers. The proportion of misinformation and potential for harm were reported for all 200 articles and their association with the number of social media engagements using a 2-sample Wilcoxon rank-sum test. All statistical tests were 2-sided. Of 200 total articles, 32.5% (n = 65) contained misinformation and 30.5% (n = 61) contained harmful information. Among articles containing misinformation, 76.9% (50 of 65) contained harmful information. The median number of engagements for articles with misinformation was greater than factual articles (median [interquartile range] = 2300 [1200-4700] vs 1600 [819-4700], P = .05). The median number of engagements for articles with harmful information was statistically significantly greater than safe articles (median [interquartile range] = 2300 [1400-4700] vs 1500 [810-4700], P = .007)., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Background: Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab., Methods: Eligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D)., Results: In total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including CD8 and LAG3 , in tumor tissue at baseline., Conclusions: Ieramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment., Trial Registration Number: NCT02460224., Competing Interests: Competing interests: PS reports honoraria and consulting/advisory roles for Deciphera, Blueprint Medicines, and Boehringer Ingelheim; consulting/advisory roles for Ellipses Pharma, Transgene, Exelixis, Medscape, Guided Clarity, Ysios Capital, Adaptimmune, Intellisphere, and Advanced Medicine; research funding for CoBioRes NV, Eisai, GI Therapeutics, Novartis, and PharmaMar; and travel expenses for Boehringer Ingelheim, MSD, and Ipsen. DSWT reports honoraria and consulting/advisory roles for Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, and Takeda; consulting/advisory roles for Bayer, AstraZeneca, Eli Lilly, and GlaxoSmithKline; and research funding for Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer, and Amgen. MigM reports honoraria and consulting/advisory roles for Roche/Genentech, Eli Lilly, Pfizer, Novartis, and Pierre-Fabre; consulting/advisory roles for AstraZeneca, Taiho Pharmaceuticals, and PharmaMar; research funding for Novartis, Roche/Genentech, and Puma; speaker’s bureau for Eli Lilly/ImClone, Roche/Genentech, and Pierre-Fabre; and other relationship with Roche/Genentech. MOdO reports honoraria for MSD. JS reports consulting/advisory roles for Astellas Pharma, AstraZeneca/MedImmune, Bayer, Eisai, Roche/Genentech, Pfizer, Immunocore, Seagen, Novartis, Sun Pharma, EMD Serono, Amgen, Bristol-Myer Squib, Flugent Therapeutics, Exelixis, Merck, Takeda, and Array BioPharma. RDC reports consulting/advisory roles and research funding for Merck, Aura Biosciences, Castle Biosciences, Immunocore, PureTech, Sorrento Therapeutics, Chimeron Bio, Regenix, InxMed, Pierre Fabre, TriSalus Life Sciences, Iovance Biotherapeutics, Oncosec, Regeneron, Genzyme, Amgen, Astellas Pharma, AstraZeneca, Bristol-Myer Squib/Medarex, Corvus Pharmaceuticals, Ideya, Mirati Therapeutics, Novartis, Pfizer, Plexxikon, and Roche/Genentech; research funding for Bayer, Bellicum Pharmaceuticals, Eli Lilly, Immunocore, Incyte, Macrogenics, Merck, Mirati Therapeutics, Array BioPharma, IDEAYA Biosciences, and Regeneron; and speaker’s bureau for Bristol-Myer Squib/Medarex.CK reports research funding for Bristol-Myers Squibb, Merus, and Gritstone Oncology. TE reports research funding for Novartis, Astellas Pharma, Sumitomo Group, Eli Lilly, Amgen, Quintiles, Daiichi Sankyo, Bayer, Eisai, IQVIA, MSD, Ono Pharmaceutical, Parexel, Nihonkayaku, and Taiho Pharmaceuticals. AP is an employee of, and reports honoraria for, Novotech; and reports research funding for Roche/Genentech, Bristol-Myers Squibb, Hutchison MediPharma, Merck, Bayer, Macrogenics, Pfizer, Akeso Biopharma, BeiGene, CStone Pharmaceuticals, Five Prime Therapeutics, CBT Pharmaceuticals, Arcus Biosciences, Corvus Pharmaceuticals, Eli Lilly, Henlius, QBiotics, Virogin, GlaxoSmithKline, Theradex, ENB Therapeutics, InxMed, Seattle Genetics, Janssen, Starpharma, and QBiotics. FDB reports honoraria and consulting/advisory roles for Roche, Pfizer, Bristol-Myers Squibb, Merk, MSD, Servier, and Sanofi; consulting/advisory roles for Incyte, Teofarma, EMD Serono, Nerviano Medical Sciences, Sanofi, and Novartis; and research funding for Novartis, Roche, Merck Serono, Pfizer, Servier, Philogen, Loxo Oncology, Tesaro, Nerviano Medical Sciences, and Kymab. RH reports honoraria and consulting/advisory roles for AstraZenca, Bristol-Myers Squibb, Eisai, Eli Lilly, Merck, MSD, Novartis, Oncosec, Pfizer, Roche and Seagen; research funding from AstraZeneca, Eli Lilly, MSD, Roche, Seagen, OncoSec, and Novartis; and travel expenses from Novartis. TZ reports immediate family connections to Capio BioSciences and Archimmume Therapeutics; these relatives also own stock at these companies and at Nanarobotics. TZ reports honoraria for Exelixis, Roche/Genentech, MJH Life Sciences, and Pacific Genuity; consulting/advisory roles for Janssen, Roche/Genentech, Sanofi, Exelixis, AstraZeneca, Pfizer, Bristol-Myers Squibb, Foundation Medicine, Pharmacyclics, Amgen, Merck, Seattle Genetics, Dendreon, and Calithera Biosciences; speaker’s Bureau for Exelixis, Roche/Genentech, Genomic Health, and Sanofi/Aventis; research funding for Astellas Pharma, Janssen, Acerta Pharma, Pfizer, Merrimack, Stem CentRx, Novartis, OmniSeq, Personal Genome Diagnostics, Regeneron, Merck, and Mirati Therapeutics; patents, royalties and other intellectual property for circulating tumor cell novel capture by c-MET technology and prochelators as Targeted Prodrugs for Prostate Cancer; and travel expenses for Acerta Pharma, Genomic Health, and AstraZeneca. RAS reports honoraria and consulting/advisory roles for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, Roche/Genentech, Takeda, Yuhan, Amgen, Bayer, and Merck; consulting/advisory roles for Taiho Pharmaceutical, Yuhan, Takeda, Amgen, and Merck; and research funding for AstraZeneca and Boehringer Ingelheim. AW reports honoraria for Eisai and Merck; consulting/advisory roles for Merck and Bristol-Myers Squibb; speaker’s bureau for Astellas Pharma and Merck; and travel expenses for Astellas Pharma, Ipsen, and Merck. JK is employed by, and reports receiving leadership fees, patents, royalties or other intellectual property for, Heidelberg ImmunoTherapeutics; and reports research funding for Vaccibody. AL, TS, VA, and EK are employees of Novartis. DG is an employee of Novartis and Mercy BioAnalytics. TS has a spouse who is employed by Teva Pharmaceuticals. NRC is an employee of, and owns stock in, Novartis. CASP was an employee of Novartis and owns stock in, holds patents, royalties, or other intellectual property in Novartis, and is also employed by, and has stock options in, Larkspur Biosciences. RR is an employee of, and holds stock in, Novartis and Takeda. TH is an employee of ViiV Healthcare, owns stock in ViiV Healthcare and Novartis, and holds patents, royalties, or other intellectual property in Novartis. PYR is an employee of, and holds stock in, Novartis. DSH owns stock in MolecularMatch, Presagia, and OncoResponse; reports consulting/advisory roles and research funding for Bayer, Guidepoint Global, Alpha Insights, Axiom Biotechnologies, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza Therapeutics, WebMD, Infinity Pharmaceuticals, Amgen, Adaptimmune, Boxer Capital, ECOR1, Tavistock, Baxter, COG, Genentech, Group H, Janssen, Acuta, HCW Precision, Infinity, Prime Oncology, and ST Cube; research funding for Daiichi Sankyo, AbbVie, Kite Pharma, MedImmune, Molecular Templates, NCI-CTEP Fate Therapeutics, Novartis, Turning Point Therapeutics, Verstatem, Kyowa, Loxo Oncology, Merck, Eisai, Genmab, Ignyta, Mirati Therapeutics, miRNA, Mologen, Takeda, AstraZeneca, Navier, VM Oncology, Erasca, Inc, Eli Lilly, Bristol-Myers Squibb, EMD Serono, GlaxoSmithKline, Millenium, and Adlai Nortye; and travel expenses for Genmab, SITC, Bayer Schering Pharma, miRNA, Loxo Oncology, Amgen, AstraZeneca, Celgene, Eli Lilly, Genentech, GlaxoSmithKline, Janssen, Pfizer, Philips, and Takeda. MicM, WA, BDB, TL, NP, and AC report no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC)., Materials and Methods: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10., Results: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK ( p = 0.01), EGFR ( p < 0.01), and TP53 ( p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21-0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21-0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation., Conclusions: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression., Competing Interests: CONFLICTS OF INTEREST University of Utah authors CW, HB, THA, JM, SU, WA, DB, and DS received research funding from BMS for their institution for the work under consideration. Site primary investigators MBS, FB, AS, MP, BX, BG, and JLV received payments to their institutions for research time dedicated to this project. JMT, SJL, MC as employees of BMS received compensation from their employer for participation in this study and in preparation of the manuscript. WA has declared research funding from Astra Zeneca. FB has declared consulting fees from BMS and payments by BMS from the speaking bureau. MP has declared payment from Bayer for presentations. DS has declared consulting fees from BMS., (Copyright: © 2022 Willis et al.)

Patients with terminal cancers commonly receive aggressive and sub-optimal treatment near the end of life, which may not be beneficial in terms of duration or quality of life. To improve end-of-life care, it is essential to develop methods that can accurately predict the short-term risk of death. However, most prediction models for patients with cancer are static in the sense that they only use patient features at a fixed time. We proposed a dynamic prediction model (DPM) that can incorporate time-dependent predictors. We apply this method to patients with advanced non-small-cell lung cancer from a real-world database. Inverse probability of censoring weighted AUC with bootstrap inference was used to compare predictions among models. We found that increasing ECOG performance status and decreasing albumin had negative prognostic associations with overall survival (OS). Moreover, the negative prognostic implications strengthened over the patient disease course. DPMs using both time-independent and time-dependent predictors substantially improved short-term prediction accuracy compared to Cox models using only predictors at a fixed time. The proposed model can be broadly applied for prediction based on longitudinal data, including an estimation of the dynamic effects of time-dependent features on OS and updating predictions at any follow-up time.

Background: Collecting, monitoring, and responding to patient-generated health data (PGHD) are associated with improved quality of life and patient satisfaction, and possibly with improved patient survival in oncology. However, the current state of adoption, types of PGHD collected, and degree of integration into electronic health records (EHRs) is unknown., Methods: The NCCN EHR Oncology Advisory Group formed a Patient-Reported Outcomes (PRO) Workgroup to perform an assessment and provide recommendations for cancer centers, researchers, and EHR vendors to advance the collection and use of PGHD in oncology. The issues were evaluated via a survey of NCCN Member Institutions. Questions were designed to assess the current state of PGHD collection, including how, what, and where PGHD are collected. Additionally, detailed questions about governance and data integration into EHRs were asked., Results: Of 28 Member Institutions surveyed, 23 responded. The collection and use of PGHD is widespread among NCCN Members Institutions (96%). Most centers (90%) embed at least some PGHD into the EHR, although challenges remain, as evidenced by 88% of respondents reporting the use of instruments not integrated. Forty-seven percent of respondents are leveraging PGHD for process automation and adherence to best evidence. Content type and integration touchpoints vary among the members, as well as governance maturity., Conclusions: The reported variability regarding PGHD suggests that it may not yet have reached its full potential for oncology care delivery. As the adoption of PGHD in oncology continues to expand, opportunities exist to enhance their utility. Among the recommendations for cancer centers is establishment of a governance process that includes patients. Researchers should consider determining which PGHD instruments confer the highest value. It is recommended that EHR vendors collaborate with cancer centers to develop solutions for the collection, interpretation, visualization, and use of PGHD.

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive malignancy that affects older adults with frequent comorbidities, making real-world treatment decisions challenging. This study compares the overall survival (OS) of patients with MPM by physician's choice of first-line (1L) platinum chemotherapy (PC), second-line (2L) immunotherapy versus chemotherapy, and by receipt of maintenance therapy (MT)., Methods: The study included patients diagnosed with advanced MPM in the Flatiron Health electronic health record-derived database who initiated PC with pemetrexed in the 1L setting between 2011 and 2019. Patients in the 2L therapy analysis received single-agent chemotherapy versus immunotherapy after the progression of disease from our 1L cohort. Patients in the MT cohort were identified on the basis of continued receipt of pemetrexed with or without bevacizumab after dropping PC at prespecified intervals. The OS of patients by choice of 1L PC, 2L immunotherapy versus chemotherapy, and receipt of MT was summarized by means of Kaplan-Meier survival estimates and compared in the context of propensity score matching weighted analyses., Results: In propensity score matching weighting analysis from 2065 patients with MPM, there was no evidence of an OS difference by choice of 1L PC (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 0.89-1.31, p  = 0.43), suggestive evidence of an OS difference by choice of 2L immunotherapy versus chemotherapy (HR = 0.68, 95% CI: 0.42-1.08; p  = 0.10), and no evidence of an OS difference by receipt of MT (HR = 0.92, 95% CI: 0.72-1.16, p  = 0.46)., Conclusions: Using real-world, propensity score-matched weighted analysis of MPM, we found there was no difference in OS by choice of 1L PC, 2L immunotherapy or chemotherapy, or by receipt of MT., (© 2022 The Authors.)