The recommended frontline therapy for patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC is osimertinib (osi), a 3rd‐generation (gen) EGFR tyrosine kinase inhibitor (TKI); however, most will develop resistance. Approximately 28% of frontline pts treated with a 1st/2nd-gen EGFR TKI die before receiving a 2nd line of therapy (LOT) (Nieva Drugs Real World Outcomes 2022; 9:333–345). This analysis estimated mortality in EGFRm NSCLC after starting frontline osi and before 2nd LOT to determine if there is an improvement to historical rates.
Data from the ConcertAI (Cambridge, MA) Patient360 NSCLC database (>100 geographically dispersed community US oncology practices) were analyzed descriptively. Included pts were diagnosed with advanced NSCLC between 1 Jan 2018 and 16 Aug 2022, had confirmed EGFR exon 19 deletions (ex19del) or exon 21 L858R mutations, and received osi (primary analysis) or 1st/2nd-gen EGFR TKI (ie, afatinib, erlotinib, or gefitinib) as frontline monotherapy.
In the ConcertAI Patient360 database, 1,135 pts had confirmed EGFR ex19del or L858R; of which 467 (41%) received osi as frontline monotherapy. Among this frontline osi population, 119 (25%) died before receiving a subsequent LOT. Documented start of a 2nd LOT was observed in 133 (28%) of frontline osi-treated pts. The remaining 215 (46%) did not have documented start of a 2nd LOT, which could be due to ongoing frontline use. A similar proportion of frontline 1st/2nd-gen EGFR TKI pts died prior to a 2nd LOT (20%;
Patient attrition
| Of patients receiving frontline, n (%) | Osimertinib (n = 467) | 1st or 2nd-gen EGFR TKI (n = 61) |
|---|---|---|
| Median follow-up | 2.1 years | 2.9 years |
| Died during frontline | 119 (25) | 12 (20) |
| No documented start of 2nd LOT | 215 (46) | 8 (13) |
| Started 2nd LOT | 133 (28) | 41 (67) |
Cross-cohort analysis was not conducted, and therefore, confounding factors cannot be ruled out.
The proportion of EGFRm NSCLC pts dying while on frontline osi (25%) remains high, demonstrating many never get to a 2nd LOT. Further optimization of frontline therapy is needed to improve patient outcomes.
Medical writing support was provided by Lumanity Communications, Inc.
The authors.
Janssen.
N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Eli Lilly, MSD, Pfizer, Roche, Takeda. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, ONO, BMS, Eli Lilly, Boehringer Ingelheim, Takeda, MSD, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Celltrion, Amgen, Nippon Kayaku, Takeda, Pfizer, ONO, Janssen, AnHeart Therapeutics Inc; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Eli Lilly, Janssen, Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Takeda, ONO; Non-Financial Interests, Personal, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Personal, Member: ASCO. T.M. Kim: Financial Interests, Personal, Advisory Role: Honoraria for lectures from AstraZeneca, IMBDx, Inc., Takeda, and Yuhan; Financial Interests, Personal, Other: AstraZeneca, Janssen, Regeneron, Samsung. L. Demirdjian: Financial Interests, Personal, Full or part-time Employment: Janssen. A.B. Bourla: Financial Interests, Personal, Full or part-time Employment: Flatiron Health/ Roche Group, Janssen R & D. A. Abdul Sultan: Financial Interests, Personal, Full or part-time Employment: Janssen. P. Mahadevia: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics.