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Translational Therapeutics

Immune biomarkers and response to checkpoint inhibition of BRAFV600 and BRAF non-V600 altered lung cancers

British Journal of Cancer volume 126, pages 889–898 (2022)Cite this article

Subjects

Abstract

Background

While 2–4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours.

Methods

Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020.

Results

In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I–III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17–6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS).

Conclusions

A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.

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Fig. 1: Overall survival of patients with lung cancers according to the type of BRAF alteration.
Fig. 2: Response to ICI according to BRAF mutation class, TMB and PD-L1 status.
Fig. 3: Time on ICI (in years) among patients with BRAF-altered lung cancer.

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Data availability

All genomic data from sequenced tumours are included in the cBioportal for Cancer Genomics repository (http://cbioportal.org/msk-impact). Relevant clinical data are included in the manuscript.

References

  1. Chen D, Zhang LQ, Huang JF, Liu K, Chuai ZR, Yang Z, et al. BRAF mutations in patients with non-small cell lung cancer: a systematic review and meta-analysis. PLoS ONE. 2014;9:e101354.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Paik PK, Arcila ME, Fara M, Sima CS, Miller VA, Kris MG, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011;29:2046–51.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cardarella S, Ogino A, Nishino M, Butaney M, Shen J, Lydon C, et al. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res. 2013;19:4532–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Marchetti A, Felicioni L, Malatesta S, Grazia Sciarrotta M, Guetti L, Chella A, et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol. 2011;29:3574–9.

    Article  CAS  PubMed  Google Scholar 

  5. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.

    Article  CAS  PubMed  Google Scholar 

  6. Lin Q, Zhang H, Ding H, Qian J, Lizaso A, Lin J, et al. The association between BRAF mutation class and clinical features in BRAF-mutant Chinese non-small cell lung cancer patients. J Transl Med. 2019;17:298.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7:596–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dankner M, Rose AAN, Rajkumar S, Siegel PM, Watson IR. Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations. Oncogene. 2018;37:3183–99.

    Article  CAS  PubMed  Google Scholar 

  9. Baik CS, Myall NJ, Wakelee HA. Targeting BRAF-mutant non-small cell lung cancer: from molecular profiling to rationally designed therapy. Oncologist. 2017;22:786–96.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Litvak AM, Paik PK, Woo KM, Sima CS, Hellmann MD, Arcila ME, et al. Clinical characteristics and course of 63 patients with BRAF mutant lung cancers. J Thorac Oncol. 2014;9:1669–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Villaruz LC, Socinski MA, Abberbock S, Berry LD, Johnson BE, Kwiatkowski DJ, et al. Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium. Cancer. 2015;121:448–56.

    Article  CAS  PubMed  Google Scholar 

  12. Kinno T, Tsuta K, Shiraishi K, Mizukami T, Suzuki M, Yoshida A, et al. Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations. Ann Oncol. 2014;25:138–42.

    Article  CAS  PubMed  Google Scholar 

  13. Yao Z, Yaeger R, Rodrik-Outmezguine VS, Tao A, Torres NM, Chang MT, et al. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature. 2017;548:234–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yao Z, Torres NM, Tao A, Gao Y, Luo L, Li Q, et al. BRAF mutants evade ERK-dependent feedback by different mechanisms that determine their sensitivity to pharmacologic inhibition. Cancer Cell. 2015;28:370–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fontana E, Valeri N. Class(y) dissection of BRAF heterogeneity: beyond non-V600. Clin Cancer Res. 2019;25:6896–8.

    Article  CAS  PubMed  Google Scholar 

  16. Dagogo-Jack I, Martinez P, Yeap BY, Ambrogio C, Ferris LA, Lydon C, et al. Impact of BRAF mutation class on disease characteristics and clinical outcomes in BRAF-mutant lung cancer. Clin Cancer Res. 2019;25:158–65.

    Article  CAS  PubMed  Google Scholar 

  17. Tissot C, Couraud S, Tanguy R, Bringuier PP, Girard N, Souquet PJ. Clinical characteristics and outcome of patients with lung cancer harboring BRAF mutations. Lung Cancer. 2016;91:23–8.

    Article  PubMed  Google Scholar 

  18. Cui G, Liu D, Li W, Fu X, Liang Y, Li Y, et al. A meta-analysis of the association between BRAF mutation and nonsmall cell lung cancer. Medicine. 2017;96:e6552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Planchard D, Besse B, Groen HJM, Souquet PJ, Quoix E, Baik CS, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17:984–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mazieres J, Cropet C, Montané L, Barlesi F, Souquet PJ, Quantin X, et al. Vemurafenib in non-small-cell lung cancer patients with BRAF(V600) and BRAF(nonV600) mutations. Ann Oncol. 2020;31:289–94.

    Article  CAS  PubMed  Google Scholar 

  21. Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17:642–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland A, et al. Dabrafenib plus trametinib in patients with previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18:1307–16.

    Article  CAS  PubMed  Google Scholar 

  23. Subbiah V, Puzanov I, Blay JY, Chau I, Lockhart AC, Raje NS, et al. Pan-cancer efficacy of vemurafenib in BRAF (V600)-mutant non-melanoma cancers. Cancer Discov. 2020;10:657–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Non-small cell lung cancer (version 2.2021) 2020. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.

  25. Dagogo-Jack I. Durable response to dabrafenib combined with trametinib in a patient with NSCLC harboring a BRAF G469A mutation. J Thorac Oncol. 2020;15:e174–e6.

    Article  CAS  PubMed  Google Scholar 

  26. Negrao MV, Raymond VM, Lanman RB, Robichaux JP, He J, Nilsson MB, et al. Molecular landscape of BRAF-mutant NSCLC reveals an association between clonality and driver mutations and identifies targetable non-V600 driver mutations. J Thorac Oncol. 2020;15:1611–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dudnik E, Peled N, Nechushtan H, Wollner M, Onn A, Agbarya A, et al. BRAF mutant lung cancer: programmed death ligand 1 expression, tumor mutational burden, microsatellite instability status, and response to immune check-point inhibitors. J Thorac Oncol. 2018;13:1128–37.

    Article  CAS  PubMed  Google Scholar 

  28. Guisier F, Dubos-Arvis C, Viñas F, Doubre H, Ricordel C, Ropert S, et al. Efficacy and safety of anti-PD-1 immunotherapy in patients with advanced NSCLC with BRAF, HER2, or MET mutations or RET translocation: GFPC 01-2018. J Thorac Oncol. 2020;15:628–36.

    Article  CAS  PubMed  Google Scholar 

  29. Mansuet-Lupo A, Alifano M, Pécuchet N, Biton J, Becht E, Goc J, et al. Intratumoral immune cell densities are associated with lung adenocarcinoma gene alterations. Am J Respir Crit Care Med. 2016;194:1403–12.

    Article  CAS  PubMed  Google Scholar 

  30. Rihawi K, Giannarelli D, Galetta D, Delmonte A, Giavarra M, Turci D, et al. BRAF mutant NSCLC and immune checkpoint inhibitors: results from a real-world experience. J Thorac Oncol. 2019;14:e57–e9.

    Article  PubMed  Google Scholar 

  31. Gainor JF, Shaw AT, Sequist LV, Fu X, Azzoli CG, Piotrowska Z, et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin Cancer Res. 2016;22:4585–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Berghoff AS, Bellosillo B, Caux C, de Langen A, Mazieres J, Normanno N, et al. Immune checkpoint inhibitor treatment in patients with oncogene- addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary round-table discussion. ESMO Open. 2019;4:e000498.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, et al. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung cancer—a meta-analysis. J Thorac Oncol. 2017;12:403–7.

    Article  PubMed  Google Scholar 

  34. Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol. 2018;36:633–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Spigel DR, Schrock AB, Fabrizio D, Frampton GM, Sun J, He J, et al. Total mutation burden (TMB) in lung cancer (LC) and relationship with response to PD-1/PD-L1 targeted therapies. J Clin Oncol. 2016;34:9017–9017.

    Article  Google Scholar 

  36. Nagahashi M, Sato S, Yuza K, Shimada Y, Ichikawa H, Watanabe S, et al. Common driver mutations and smoking history affect tumor mutation burden in lung adenocarcinoma. J Surg Res. 2018;230:181–5.

    Article  PubMed  Google Scholar 

  37. Offin M, Rizvi H, Tenet M, Ni A, Sanchez-Vega F, Li BT, et al. Tumor mutation burden and efficacy of EGFR-tyrosine kinase inhibitors in patients with EGFR-mutant lung cancers. Clin Cancer Res. 2019;25:1063–9.

    Article  CAS  PubMed  Google Scholar 

  38. Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30:1321–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cheng DT, Mitchell TN, Zehir A, Shah RH, Benayed R, Syed A, et al. Memorial Sloan Kettering-integrated mutation profiling of actionable cancer targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17:251–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51:202–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Vokes NI, Liu D, Ricciuti B, Jimenez-Aguilar E, Rizvi H, Dietlein F, et al. Harmonization of tumor mutational burden quantification and association with response to immune checkpoint blockade in non-small-cell lung cancer. JCO Precis Oncol. 2019;3:1–12.

  42. Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N. Engl J Med. 2018;378:2093–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gaule P, Smithy JW, Toki M, Rehman J, Patell-Socha F, Cougot D, et al. A quantitative comparison of antibodies to programmed cell death 1 ligand 1. JAMA Oncol. 2017;3:256–9.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N. Engl J Med. 2018;378:2078–92.

    Article  CAS  PubMed  Google Scholar 

  45. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl J Med. 2016;375:1823–33.

    Article  CAS  PubMed  Google Scholar 

  46. Shen R, Martin A, Ni A, Hellmann M, Arbour KC, Jordan E, et al. Harnessing clinical sequencing data for survival stratification of patients with metastatic lung adenocarcinomas. JCO Precis Oncol. 2019;3:1–9.

    CAS  PubMed  Google Scholar 

  47. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl J Med. 2019;381:1535–46.

    Article  CAS  PubMed  Google Scholar 

  48. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl J Med. 2015;372:2521–32.

    Article  CAS  PubMed  Google Scholar 

  49. Planchard D, Besse B, Groen HJM, Souquet P-J, Quoix E, Baik CS, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17:984–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23:703–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

YRMG gratefully acknowledges receipt of the Kristina M. Day Young Investigator Award from Conquer Cancer, the ASCO Foundation. She has received training as part of an institutional K30 grant from the National Cancer Institute (CTSA #UL1TR00457). The authors acknowledge funding for Memorial Sloan Kettering Cancer Center received through the NIH/NCI institutional P30 CA008748 grant. The authors appreciate the editorial and administrative contributions of Clare Wilhelm, Reeja Thomas and Jessica Moore.

Funding

This research was supported in part by the National Cancer Institute of the National Institutes of Health P30 CA008748.

Author information

Author notes

  1. These authors contributed equally: Yonina R. Murciano-Goroff, Terry Pak.

Authors and Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Yonina R. Murciano-Goroff, Sebastian Mondaca, Mark G. Kris, Paul K. Paik, Gregory J. Riely, Helena A. Yu, Charles M. Rudin, Matthew D. Hellmann, Piro Lito, Rona Yaeger, Alexander Drilon, Bob T. Li & Michael Offin

  2. Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Terry Pak, Stephanie L. Wu, Josiah D. Land, Larry W. Buie & Dazhi Liu

  3. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jessica R. Flynn & Glenn Heller

  4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Joseph Montecalvo & Natasha Rekhtman

  5. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Darragh Halpenny & Andrew J. Plodkowski

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Contributions

MO and BTL conceived of/ designed the study. YRMG, TP, SM, DH, AJP, DL and MO acquired the data. All authors were involved in data analysis and/or interpretation. YRMG and MO drafted the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Michael Offin.

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This study was approved by the institutional review board of Memorial Sloan Kettering Cancer Center.

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Not applicable.

Competing interests

MSK was awarded grants from the National Institutes of Health/National Cancer Institute during the conduct of the study. YRMG acknowledges receipt of travel, accommodation, and expenses from AstraZeneca. MGK reports personal fees from AstraZeneca, Pfizer, Regeneron, Daiichi Sankyo, outside the submitted work; he has received honoraria for participation in educational programs from WebMD, OncLive, Physicians Education Resources, Prime Oncology, Intellisphere, Creative Educational Concepts, Peerview, i3 Health, Paradigm Medical Communications, AXIS, Carvive Systems, AstraZeneca, and Research to Practice. Funds for travel and lodging, and food and beverage have been provided by AstraZeneca, Pfizer, Regeneron, and Genentech. Dr. Kris is an employee of Memorial Sloan Kettering. Memorial Sloan Kettering has received research funding from The National Cancer Institute (USA), The Lung Cancer Research Foundation, Genentech Roche, and PUMA Biotechnology for research conducted by Dr. Kris. Memorial Sloan Kettering has an institutional agreement with IBM for Watson For Oncology and receives royalties from IBM. MSK has licensed testing for EGFR T790M to MolecularMD. PKP reports grants and personal fees from Celgene; personal fees from Takeda, Abbvie, Lilly, Boehringer Ingelheim, EMD Serono, Calithera, Bicara, Xencor, GlaxoSmithKline, AstraZeneca, outside the submitted work. GJR reports grants from Novartis, Roche, Genentech, Millennium, GlaxoSmithKline, Pfizer, Infinity Pharmaceuticals, ARIAD; non-financial support from Merck Sharp & Dohme, outside the submitted work. In addition, Dr. Riely has a patent US20170273982A1 pending, and a patent WO2017164887A8 pending. HAY reports grants and personal fees from AstraZeneca and Daiichi; grants and non-financial support from Lilly, grants from Novartis, Pfizer, and Cullinan; personal fees from Blueprint Medicine, Janssen, outside the submitted work. In addition, Dr. Yu has a patent US20170273982A1 pending, and a patent WO2017164887A1 pending. CMR reports personal fees from AbbVie, Amgen, Ascentage, AstraZeneca, Bicycle, Celgene, Daiichi Sankyo, Genentech/Roche, Ipsen, Jansen, Jazz, Lilly/Loxo, Pfizer, PharmaMar, Syros, Vavotek, Bridge Medicines, Harpoon Therapeutics, and Earli outside the submitted work. M.D.H. reports personal fees from AstraZeneca/MedImmune; grants and personal fees from Bristol-Myers Squibb; personal fees from Merck, Genentech/Roche, Novartis, Janssen Pharmaceuticals, Nektar, Syndax Pharmaceuticals, Mirati Therapeutics, Shattuck Labs, outside the submitted work. In addition, Dr. Hellmann has a patent PCT/US2015/062208 pending and Stock and Other Ownership Interests: Shattuck Labs; Dr. Hellman is a Damon Runyon Clinical Investigator supported (in part) by the Damon Runyon Cancer Research Foundation (CI-98-18) and is a member of the Parker Institute for Cancer Immunotherapy. LWB reports personal fees from Amgen, Jazz Pharmaceuticals, Heron, Pfizer, outside the submitted work. PL reports research support to MSK from Mirati, Revolution Medicines, Amgen and Strategia during the conduct of the study. Dr Lito is listed as an inventor on patent applications filed by MSKCC describing therapeutic interventions for BRAF or KRAS mutant tumours. Dr. Lito is supported in part by the NIH/NCI (1R01CA230745-01 and 1R01CA230267-01A1), the Pew Charitable Trusts and the Damon Runyon Cancer Research Foundation. AD reports personal fees from Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, Abbvie, 14ner/Elevation Oncology, Remedica Ltd., ArcherDX, Monopteros, Elevation Oncology, Novartis, EMD Serono, Melendi, Faculty RTP, Repare RX, Pfizer, Liberum, outside the submitted work; and Associated research paid to MSK from Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; research from Foundation Medicine; royalties from Wolters Kluwer; other support from Merck, Puma, Merus, Boehringer Ingelheim; Únd CME honoraria from Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis, Peerview Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options. DL reports personal fees from Pfizer, Heron Therapeutics, outside the submitted work. BTL reports non-financial support from Amgen, Genentech, and Boehringer Ingelheim; grants and non-financial support from Lilly, AstraZeneca, Daiichi Sankyo; grants and personal fees from Guardant Health, Hengrui Therapeutics, MORE Health; grants from Amgen, Illumina, GRAIL, Bolt Biotherapeutics; personal fees from Resolution Bioscience, Jiangsu Hengrui Medicine, outside the submitted work; Dr. Li is an inventor on two institutional patents at MSK and has intellectual property rights as a book author at Karger Publishers. The remaining authors declare no competing interests.

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Murciano-Goroff, Y.R., Pak, T., Mondaca, S. et al. Immune biomarkers and response to checkpoint inhibition of BRAFV600 and BRAF non-V600 altered lung cancers. Br J Cancer 126, 889–898 (2022). https://doi.org/10.1038/s41416-021-01679-1

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