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FOR A METASTATIC NSCLC PATIENT

HE HAS

ONE CHANCE

AT FIRST-LINE THERAPY

Knowing his mutation status may mean the difference between getting the right first-line treatment or not

ARE YOU SURE YOU MADE THE RIGHT CHOICE?

TEST EVERY mNSCLC PATIENT

In metastatic NSCLC

ONE MISSED PATIENT
IS ONE TOO MANY

BE SURE your patients get all the molecular testing they need

 

~1 IN 3 patients with lung adenocarcinoma has an actionable mutation1-3

 

BE SURE to test all mNSCLC patients for oncogenic mutations, regardless of phenotype

  • National Comprehensive Cancer Network® (NCCN®) recommends clinicopathologic features such as ethnicity, smoking status, or histology NOT be used to select patients for EGFR mutational testing4

BE SURE. Don’t settle for an unknown molecular status

  • NCCN recommends that repeat biopsy and/or plasma testing should be done if initial biopsy is insufficient, if feasible4
RET has recently been added as an actionable mutation.4,5

BE SURE to test all mNSCLC patients for oncogenic mutations, regardless of phenotype

  • National Comprehensive Cancer Network® (NCCN®) recommends clinicopathologic features such as ethnicity, smoking status, or histology NOT be used to select patients for EGFR mutational testing4

BE SURE. Don’t settle for an unknown molecular status

  • NCCN recommends that repeat biopsy and/or plasma testing should be done if initial biopsy is insufficient, if feasible4
RET has recently been added as an actionable mutation.4,5
* Based on 3 studies of patients with adenocarcinoma; Sholl et al (2015) included 733 patients with lung adenocarcinoma but did not test patients for ROS1 rearrangements or NTRK fusions.1-3
Percentage adjusted based on aggregate of Sholl et al, Stransky et al, and Bergethon et al.
To be sure of your first-line treatment choice is to know their full molecular profile first

KNOW MUTATION STATUS BEFORE INITIATING FIRST-LINE IMMUNOTHERAPY

KNOW BEFORE IO

IN METASTATIC NSCLC WITH ACTIONABLE MUTATIONS,
START WITH GUIDELINE-RECOMMENDED TARGETED THERAPY

IMMUNOTHERAPY IS NOT

AN APPROPRIATE FIRST-LINE CHOICE

Sequential immunotherapy (IO) followed by TKI treatment could harm patients with targetable mNSCLC6-8‡

Based on 3 studies of 649 NSCLC patients with actionable mutations treated with immunotherapy followed by TKIs. Adverse reactions, including ILD, were observed following the sequential use of IO followed by TKI therapy in patients with mNSCLC who had actionable mutations.6-8

ARE YOU TREATING WITH IO BEFORE YOU KNOW MUTATION STATUS?

In patients with actionable mutations in metastatic NSCLC

PD-L1 EXPRESSION IS IRRELEVANT TO FIRST-LINE TREATMENT9

NCCN NCCN NCCN recommends that patients with mNSCLC and PD-L1 expression levels ≥1% be confirmed EGFR, ALK, BRAF, ROS1, MET exon 14 skipping, NTRK1/2/3, and RET negative before they are treated with immune checkpoint inhibitors.
  • According to 2021 ASCO Guidelines, first-line targeted therapy is recommended for patients with stage IV NSCLC and an actionable mutation10

IN FIRST-LINE TREATMENT OF METASTATIC NSCLC WITH AN ACTIONABLE MUTATION, IMMUNOTHERAPY IS

Crossed Out IconNOT SEQUENTIALLY SAFE Treatment with TKIs after IO may increase risk of toxicity6-8II

Crossed Out IconNOT INDICATED First-line indications for IO exclude patients with EGFR or ALK mutations11-13

Crossed Out IconNOT TARGETED THERAPY IO does not target the driver of disease

Crossed Out IconNOT EFFECTIVE In a study of IO in treatment-naïve EGFRm patients, ORR was 0%14¶

  • 11 large, pivotal first-line IO trials—including studies of pembrolizumab, nivolumab, and atezolizumab—did not allow treatment-naïve EGFRm or ALK+ patients15-26#
Thumbs Down Icon

In patients with mNSCLC and an actionable mutation, first-line IO is not guideline recommended

§The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays or commercial laboratories.4
II Based on 3 studies of 649 NSCLC patients with actionable mutations treated with immunotherapy followed by TKIs. Adverse reactions, including ILD, were observed following the sequential use of IO followed by TKI therapy in patients with mNSCLC who had actionable mutations.6-8
Phase 2, single-arm study of pembrolizumab in patients with advanced EGFRm NSCLC. 82% of enrolled patients were treatment naïve. No responses were observed in the 10 of 11 patients treated, even in patients with PD-L1 expression ≥50%. The patient who did have a response was revealed to be EGFR wild-type upon repeat analysis.14
# KEYNOTE-024, KEYNOTE-042, KEYNOTE-021 Cohort G, KEYNOTE-189, CHECKMATE 026, CHECKMATE 227, CHECKMATE 9LA, IMpower110, IMpower130, IMpower132, and IMpower150 did not allow patients with treatment-naïve metastatic EGFRm NSCLC. In the IMpower130 and IMpower150 trials, EGFRm patients were allowed only after progression on EGFR-TKI therapy or intolerance to EGFR-TKI treatment. There are no head-to-head trials comparing IO and EGFR- or ALK-TKIs in patients with EGFR or ALK mutation–positive mNSCLC.15-26
Confirm mutation negative—IO use followed by TKIs could be unsafe if your mNSCLC patient has an actionable mutation

IF YOUR mNSCLC PATIENT IS MUTATION POSITIVE,
START WITH GUIDELINE-RECOMMENDED TARGETED THERAPY

In a clinical study of patients with actionable mutations in metastatic NSCLC

TARGETED THERAPY SIGNIFICANTLY
IMPROVED OVERALL SURVIVAL

Purple and White Check Icon

Confirming mutational status and treating with targeted therapy may give your eligible patients the best chance for a longer life

OVERALL SURVIVAL IN mNSCLC PATIENTS WITH AN ONCOGENIC DRIVER TREATED WITH OR WITHOUT TARGETED THERAPY AND PATIENTS WITH NO ACTIONABLE MUTATION27**

Overall survival in mNSCLC patients with an oncogenic driver treated with or without targeted therapy and in mNSCLC patients with no actionable mutation28

Overall survival in mNSCLC patients with an oncogenic driver treated with or without targeted therapy and in mNSCLC patients with no actionable mutation28

Median overall survival (95% CI): Actionable mutation + targeted therapy, 3.49 years (3.02-4.33); actionable mutation + no targeted therapy, 2.38 years (1.81-2.93); no actionable mutation, 2.08 years (1.84-2.46).

** Multicenter US study of 1017 patients with metastatic lung adenocarcinoma to determine the frequency of 10 oncogenic drivers including MET amplifications, ALK rearrangements, and EGFR alterations.27
When you find an actionable mutation, treat first with guideline-recommended targeted therapy—it may lead to
a longer life

FOR OPTIMAL TREATMENT SELECTION, TEST, KNOW, TREAT

In patients with mNSCLC and an actionable mutation

CHOOSE FIRST-LINE GUIDELINE-RECOMMENDED TARGETED THERAPY, NOT IO—IT’S YOUR PATIENT’S BEST CHANCE AT A LONGER LIFE

Yellow and Black Check IconTEST

all eligible patients with mNSCLC for actionable mutations to see if targeted therapy is appropriate4††

Yellow and Black Check IconKNOW

if your patient is mutation negative before choosing IO because it is not guideline recommended in first line for patients with actionable mutations4

Yellow and Black Check IconTREAT

mutation-positive patients with first-line targeted therapy because it may lead to a longer life27

NCCNNCCN NCCN recommends treatment with targeted therapy take precedence over treatment with immunotherapy in patients with mNSCLC and certain oncogenic drivers, even when PD-L1 expression levels are elevated.4
†† Molecular testing is recommended for nonsquamous mNSCLC and mNSCLC not otherwise specified; testing can be considered for patients with metastatic squamous NSCLC.4

TO BE SURE YOU KNOW THEIR FULL MOLECULAR PROFILE, COMBINE TISSUE AND LIQUID BIOPSY

INTEGRATE LIQUID BIOPSY

In metastatic NSCLC

INTEGRATE LIQUID BIOPSY

TO BE SURE OF THEIR STATUS

Optimal treatment starts with knowing the driver of their disease

ARE YOU USING BOTH TISSUE AND LIQUID BIOPSY?

In metastatic NSCLC

LIQUID BIOPSY PLUS TISSUE TESTING ARE CRITICAL TO FINDING MORE ACTIONABLE MUTATIONS‡‡

LIQUID BIOPSY CAN HELP YOU BE SURE OF YOUR PATIENT’S STATUS

Boxed Check Mark
In cases of QNS (quantity not sufficient)
In patients with tissue QNS, ~28% were found to have actionable mutations with liquid biopsy28§§
Boxed Check Mark
When tissue is not feasible
In patients who were unable to have a tissue biopsy, ~23% were found to have actionable mutations with liquid biopsy28§§
Boxed Check Mark
When fast turnaround time is critical
Liquid biopsy results were received within a median of 9 days, according to a clinical study29IIII¶¶
  
Use both liquid biopsy and tissue to help make a difference for every mNSCLC patient identified

Use both liquid biopsy and tissue testing to help make a difference for every mNSCLC patient identified

  • Liquid biopsy and tissue testing together increased detection of actionable mutations by 17% over mutations found in tissue alone28
‡‡If plasma test is negative, consider reflexing to tissue testing.30
§§ Single-center prospective US study of 323 patients with stage IV NSCLC using next-generation sequencing as the testing platform.28
IIII Multicenter US study of 323 patients with stage IIIB or IV NSCLC using next-generation sequencing as the testing platform.29
¶¶ TAT is for next-generation sequencing.

ALK, anaplastic lymphoma kinase; ASCO, American Society of Clinical Oncology; BRAF, B-Raf proto-oncogene; CI, confidence interval; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, erythroblastic oncogene B 2; ILD, interstitial lung disease; KRAS, Kirsten rat sarcoma viral oncogene; MEK1, mitogen-activated protein kinase 1; MET, mesenchymal-epithelial transition; mNSCLC, metastatic non-small cell lung cancer; NRAS, neuroblastoma RAS viral oncogene homolog; NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; ORR, overall response rate; PD-L1, programmed death-ligand 1; PIK3CA, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; QNS, quantity not sufficient; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1; TAT, turnaround time; TKI, tyrosine kinase inhibitor.

References: 1. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777. 2. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846. doi:10.1038/ncomms5846. 3. Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8):863-870. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.4.2021. ©National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 3, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Kohno T, Ichikawa H, Totoki Y, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012;18(3):375-377. 6. Oshima Y, Tanimoto T, Yuji K, Tojo A. EGFR-TKI-associated interstitial pneumonitis in nivolumab-treated patients with non-small cell lung cancer. JAMA Oncol. 2018;4(8):1112-1115. 7. Schoenfeld AJ, Arbour KC, Rizvi H, et al. Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. Ann Oncol. 2019;30(5):839-844. 8. Lin JJ, Chin E, Yeap BY, et al. Increased hepatotoxicity associated with sequential immune checkpoint inhibitor and crizotinib therapy in patients with non-small cell lung cancer. J Thorac Oncol. 2019;14(1):135-140. 9. Brahmer JR, Govindan R, Anders RA, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC). J Immunother Cancer. 2018;6(1):75. 10. Hanna NH, Robinson AG, Temin S, et al. Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol. 2021;39(9):1040-1091. 11. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2020. 12. Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2021. 13. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc.; 2021. 14. Lisberg A, Cummings A, Goldman JW, et al. A phase II study of pembrolizumab in EGFR-mutant, PD-L1+, tyrosine kinase inhibitor naïve patients with advanced NSCLC. J Thorac Oncol. 2018;13(8):1138-1145. 15. Reck M, Rodríguez-Abreu D, Robinson AG, et al; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1–positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. 16. Clinicaltrials.gov. Study of MK-3475 (pembrolizumab) versus platinum-based chemotherapy for participants with PD-L1-positive advanced or metastatic non-small cell lung cancer (MK-3475-042/KEYNOTE-042). https://clinicaltrials.gov/ct2/show/NCT02220894. Accessed July 1, 2020. 17. Langer CJ, Gadgeel SM, Borghaei H, et al; KEYNOTE-021 Investigators. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508. 18. Broderick JM. Frontline pembrolizumab combo improves survival in phase III NSCLC trial. https://www.onclive.com/web-exclusives/frontline-pembrolizumab-combo-improves-survival-in-phase-iii-nsclc-trial. Published January 16, 2018. Accessed July 1, 2020. 19. Carbone DP, Reck M, Paz-Ares L, et al; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non–small-cell lung cancer. N Engl J Med. 2017;376(25):2415-2426. 20. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-2104. 21. Clinicaltrials.gov. A study of nivolumab and ipilimumab combined with chemotherapy compared to chemotherapy alone in first line NSCLC (CheckMate 9LA). https://clinicaltrials.gov/ct2/show/NCT03215706. Accessed July 1, 2020. 22. EU Clinical Trials Register. A phase III multicenter, randomized, open-label study evaluating the efficacy and safety of atezolizumab (MPDL3280A, anti-PD-L1 antibody) in combination with carboplatin+nab-paclitaxel for chemotherapy-naive patients with stage IV non-squamous non-small cell lung cancer. EudraCT number 2014-003206-32. 23. Kowanetz M, Socinski MA, Zou W, et al. IMpower150: efficacy of atezolizumab plus bevacizumab and chemotherapy across PD-L1 expression subgroups defined by the SP142 and SP263 IHC assays confirm all-comer benefit in 1L metastatic NSCLC. Presented at: AACR; April 14-18, 2018; Chicago, IL. 24. Papadimitrakopoulou VA, Cobo M, Bordoni R, et al. IMpower132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC [oral presentation]. Presented at: IASLC WCLC; September 23-26, 2018; Toronto, Canada. 25. Spigel D, de Marinis F, Giaccone G, et al. IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC. Presented at: European Society for Medical Oncology; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA78. 26. Clinicaltrials.gov. A study of atezolizumab (MPDL3280A) compared with a platinum agent (cisplatin or carboplatin) + (pemetrexed or gemcitabine) in participants with stage IV non-squamous or squamous non-small cell lung cancer (NSCLC) [IMpower110]. https://clinicaltrials.gov/ct2/show/NCT02409342. Accessed July 1, 2020. 27. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. 28. Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173-180. 29. Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed non-small cell lung cancer. Clin Cancer Res. 2019;25(15):4691-4700. 30. Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631-1641.

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Lung Cancer and COVID-19

Resources from GO2 Foundation for Lung Cancer

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