Abstract 1301P
Background
In the treatment of aNSCLC there is increasing tension between empiric combination Tx vs precision Tx enabled by timely CGP. While elevated PD-L1 IHC may select for immune checkpoint inhibitor (ICI) benefit, concurrent EGFR/ALK/RET drivers indicate ICI resistance. Studying a RW aNSCLC clinicogenomic database (CGDB), we hypothesized that Tx prior to receipt of CGP results would enrich for chemo-based regimens (+/- ICI), while Tx after CGP results would enrich for precision approaches like matched targeted therapy (mTT) or ICI alone.
Methods
Pts with aNSCLC were selected from the Flatiron Health-Foundation Medicine (FH-FM) CGDB, a nationwide (US-based) de-identified EHR-derived clinical DB linked to FM CGP (9/2015-12/2020). To study impact of CGP results, we assessed pts without prior genotyping or Tx who received PD-L1 results ≤15 days prior to CGP results and studied whether Tx was initiated before or after CGP results. PD-L1 IHC was performed by FM using Dako 22C3 using tumor proportion scoring (TPS); CGP was done using FoundationOne or FoundationOneCDx.
Results
We selected 608 pts who received PD-L1+ IHC results (TPS ≥1%) before CGP results (median 7 days, range 1-15). In 525 (86%) pts initiating Tx after receipt of CGP results, 51% received precision Tx (37% ICI, 14% mTT) while in 83 (14%) pts who initiated Tx before CGP results, 76% received a chemo-based regimen (33% chemo + ICI, 43% chemo alone). Furthermore, when limited to 323 pts with high PD-L1 (TPS ≥50%), pts initiating Tx after receipt of CGP remained enriched for precision Tx, defined as monotherapy ICI or mTT, (65%) vs those initiating tx before CGP (34%). Notably, of 94 (15%) pts with CGP positive for a companion diagnostic (CDx) driver, 76% received mTT, highlighting the need for further education to fully enable actionability.
Conclusions
In pts with aNSCLC and ≥1% PD-L1 IHC undergoing tissue CGP, the majority of pts initiate Tx after CGP results with 51% receiving precision therapy. In the minority who initiate Tx before CGP results, chemo-based therapy is more common. Strategies to enable timely receipt of CGP results offer the potential to maximize access to precision therapies like mTT and ICI in aNSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Foundation Medicine.
Funding
Foundation Medicine.
Disclosure
A.M. VanderWalde: Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: ConcertAI; Financial Interests, Personal, Advisory Role: Elsevier; Financial Interests, Personal, Advisory Role: George Clinical; Financial Interests, Personal, Advisory Role: Caris Life Sciences; Financial Interests, Personal, Advisory Board: Mirati. J. Lee: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. K. Tolba: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. A. Ward: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. M. Cooper: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine. R.S.P. Huang: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. J. Venstrom: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. G. Oxnard: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. A.B. Schrock: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. L. Schwartzberg: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Helsinn; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Spectrum; Financial Interests, Personal, Funding: Amgen; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Puma.