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Multicenter Study
. 2024 Dec;33(12):e70049.
doi: 10.1002/pds.70049.

Determining Line of Therapy from Real-World Data in Non-Small Cell Lung Cancer

Connor B Grady  1 , Wei-Ting Hwang  1 , Joshua E Reuss  2 , Wade Iams  3 , Amanda Cass  3 , Geoffrey Liu  4 , Devalben Patel  4 , Stephen V Liu  2 , Gabriela Liliana Bravo Montenegro  2 , Tejas Patil  5 , Jorge J Nieva  6 , Amanda Herrmann  6 , Kristen A Marrone  7 , Vincent K Lam  7 , William Schwartzman  8 , Jonathan Dowell  8 , Liza C Villaruz  9 , Kelsey Leigh Miller  10 , Jared Weiss  10 , Fangdi Sun  11 , Vamsidhar Velcheti  12 , D Ross Camidge  5 , Charu Aggarwal  13 , Lova Sun  13 , Melina E Marmarelis  13
Affiliations
Multicenter Study

Determining Line of Therapy from Real-World Data in Non-Small Cell Lung Cancer

Connor B Grady et al. Pharmacoepidemiol Drug Saf. 2024 Dec.

Abstract

Introduction: Determining lines of therapy (LOT) using real-world data is crucial to inform clinical decisions and support clinical research. Existing rules for determining LOT in patients with metastatic non-small cell lung cancer (mNSCLC) do not incorporate the growing number of targeted therapies used in treatment today. Therefore, we propose rules for determining LOT from real-world data of patients with mNSCLC treated with targeted therapies.

Methods: LOT rules were developed through expert consensus using a real-world cohort of 550 patients with ALK+ or ROS1+ mNSCLC in the multi-institutional, electronic medical record-based Academic Thoracic Oncology Medical Investigators Consortium's (ATOMIC) Driver Mutation Registry. Rules were subsequently modified based on a review of appropriate LOT determination. These resulting rules were then applied to an independent cohort of patients with EGFR+ mNSCLC to illustrate their use.

Results: Six rules for determining LOTs were developed. Among 1133 patients with EGFR mutations and mNSCLC, a total of 3168 regimens were recorded with a median of 2 regimens per patient (IQR, 1-4; range, 1-13). After applying our rules, there were 2834 total LOTs with a median of 2 LOTs per patient (IQR, 1-3; range, 1-11). Rules 1-3 kept 11% of regimen changes from advancing the LOT. When compared to previously published rules, LOT assignments differed 5.7% of the time, mostly in LOTs with targeted therapy.

Conclusion: These rules provide an updated framework to evaluate current treatment patterns, accounting for the increased use of targeted therapies in patients with mNSCLC, and promote standardization of methods for determining LOT from real-world data.

Keywords: ALK; EGFR; ROS1; non‐small cell lung cancer; real‐world data.

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Conflict of interest statement

C.B.G., W.‐T.H., A.C., G.L., D.P., G.L.B.M., A.H., W.S., J.D., K.L.M., V.V., D.R.C. declare no conflicts of interest. J.E.R.: Advisory Board/Consultant: Genentech/Roche, Sanofi/Genzyme, Personalis, Guardant, AstraZeneca, BMS, Arcus, AbbVie, Daiichi Sankyo. Research Funding (to institution): Genentech/Roche, Verastem, Nuvalent, Mesothelioma Applied Research Foundation, LUNGevity Foundation. Honoraria/Speaking Fees: AstraZeneca, Merck. W.I.: Consultant for OncLive, Clinical Care Options, Chardan, Cello Health, Curio Science. Advisory Board/DSMC for Genentech, Mirati, Outcomes Insights, Jazz Pharmaceuticals, GI Therapeutics, Takeda, AstraZeneca, Sanofi, Janssen, Amgen, Bristol Myers Squibb, Novocure. S.V.L.: Advisory Board/Consultant for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Mirati, Novartis, Regeneron, Sanofi, Takeda, Turning Point Therapeutics. Research grant (to institution) from Alkermes, Elevation Oncology, Genentech, Gilead, Merck, Merus, Nuvalent, RAPT, Turning Point Therapeutics. Data Safety Monitoring Board for Candel Therapeutics. T.P.: Advisory Role (advisory boards or consultations) in last 3 years: AstraZeneca, Biocept, Boehringer Ingelheim, Bristol‐Myers Squibb, Bicara, Caris, Guardant Health, Guidepoint, EMD Serono, Janssen, Jazz Pharmaceuticals, Mirati Therapeutics, Natera, Pfizer, Sanofi, Regeneron, Roche/Genentech, Takeda. Advisory Committees: Elevation Oncology (DSMB). Research Funding: EMD Serono, Janssen, Gilead. J.J.N.: Stock/Ownership interests in Epic Sciences, Cansera, Quantagene, Indee P/L. Consulting for AstraZeneca, Naveris, Aadi biosciences, Atla, MindMed, ANP Technologies. Research funding to institution from Merck, Genentech. Patent pending on movement and unexpected healthcare encounters. K.A.M. has received consulting/advisory fees from AstraZeneca, Amgen, Janssen, Mirati Therapeutics, Daiichi Sankyo/Lilly and Puma Biotechnology, as well as Honoraria from AstraZeneca. KAM receives research funding to Johns Hopkins University from Bristol‐Myers Squibb and Mirati Therapeutics. V.K.L. reports serving in a consultant/advisory role for Seattle Genetics, Bristol‐Myers Squibb, AstraZeneca, Guardant Health, Takeda, and AnHeart Therapeutics, and has received research funding from BMS, Merck, Seattle Genetics, Astra Zeneca. L.C.V. reports researching funding from Janssen, BMS, Merck, Regeneron, GSK, AstraZeneca, BioAtla, Black Daimon Therapeutics, Jazz, Genentech, BeiGene. Consulting fees from Takeda, Janssen, InterVenn Biosciences, Sanofi, Daiichi Sankyo, Jazz, BMS, Gilead. C.A. reports receiving institutional research funding from AstraZeneca, Genentech, Incyte, MacroGenics, Medimmune, and Merck Sharp & Dohme, and receiving consultation fees from Genentech, Lilly, Celgene Merck, AstraZeneca, Blueprint Genetics, Shionogi, Daiichi Sankyo/Astra Zeneca, Regeneron/Sanofi, Eisai, BeiGene, Turning Point, Pfizer, Janssen, Boehringer Ingelheim. L.S. reports research funding from Blueprint (Inst), Seagen (Inst), IO Biotech (Inst), Erasca (Inst). Consulting with Sanofi Genzyme, Regeneron, Genmab, Seagen, and Bayer. M.E.M. reports researching funding from Eli Lilly (Inst), AstraZeneca (Inst), Merck (Inst), Genentech (Inst) consulting role with Astra Zeneca, Novocure, Boehringer Ingelheim, Janssen, Takeda, Blueprint Pharmaceuticals, Bayer, Bristol Myers Squibb, Ikena; Honorarium from Thermo Fisher; stock in Merck, Johnson & Johnson.

Figures

FIGURE 1
FIGURE 1
Algorithm for line of therapy determination.
See this image and copyright information in PMC

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