1381P - TOGETHER: Pooled real-world datasets of METex14 skipping NSCLC and adjusted comparison of upfront (chemo-)immunotherapy with tepotinib from VISION

Background

The TOGETHER study was designed for flexible pooling of METex14 skipping non-small cell lung cancer (NSCLC) patient (pt) datasets to characterize real-world (rw) outcomes before approval of MET inhibitors.

Methods

Seven datasets were used to analyze rw progression-free (rwPFS) and overall (rwOS) survival in advanced NSCLC with METex14 skipping according to Kaplan-Meier. Indirect treatment comparisons (ITC) were performed with propensity score reweighting of pts who received first-line (1L) immunotherapy (IO) alone or with chemotherapy (chemo) to match the characteristics of 111 pts with positive tissue biopsies (T+) who received 1L tepotinib in the VISION study (NCT02864992; data cut: Nov 2022).

Results

As of Jan 2023, TOGETHER included 309 pts (mean [SD] age 71.1 [9.7] years, 48% male, 52% with smoking history [SM]), with 615 lines of therapy administered between 2004 and 2022. For 1L IO+chemo (n=26; mean age 66.8 [SD 12.4], 65% SM) median rwPFS in TOGETHER was 5.7 months (95% CI: 3.1, 17.5) before and 6.9 mo (95% CI: 5.7, 29.4) after weighting, compared with 15.9 mo (95% CI: 11.3 , ne) for 1L tepotinib (HR 0.52 [0.29, 0.93]; p=0.03). For 1L IO monotherapy (n=48; mean age 73.2 [SD 9.1], 67% SM), median rwPFS in TOGETHER was 3.9 mo (95% CI: 2.7, 7.1) before and 3.4 mo (95% CI: 2.0, 9.7) after weighting compared with 15.9 mo for 1L tepotinib (HR 0.37 [0.24, 0.58]; p<0.01). Although confounded by subsequent treatments, median OS was also longer for tepotinib with 29.7 mo (95% CI: 19.1, ne) compared with 22.1 mo (95% CI: 12.6, ne) for IO+chemo (HR 0.77; p=0.38) and 18.9 mo (HR 0.64; p=0.05) for IO monotherapy. Other rw 1L treatments were chemo (n=128; mean age 69.3 [SD 9.5], 55% SM) with a median rwPFS of 4.8 mo (95% CI: 4.1, 6.2), and crizotinib (n=62; mean age 74.6 [SD 11.0], 56% SM) with a median rwPFS of 7.4 mo (95% CI: 4.4, 10.9). Median rwPFS was shorter for 2L+ chemo (4.3 mo, n=95) or 2L+ IO monotherapy (3.3 mo, n=83), and longer for 2L+ crizotinib (8.1 mo, n=68).

Conclusions

This large retrospective analysis shows poor rw outcomes for METex14 skipping NSCLC pts under standard treatments prior to the uptake of novel MET inhibitors. Matched ITC suggests longer PFS and OS with 1L tepotinib compared with 1L IO+chemo or IO monotherapy.

Clinical trial identification

NCT02864992.

Editorial acknowledgement

Medical writing assistance (funded by the Merck Healthcare KGaA, Darmstadt, Germany) was provided by Syneos Health, London, UK.

Legal entity responsible for the study

Merck Healthcare KGaA, Darmstadt, Germany.

Funding

Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Disclosure

P. Christopoulos: Financial Interests, Personal, Research Funding: Amgen, AstraZeneca, Boehringer Ingelheim, Merck Healthcare KGaA, Darmstadt, Germany, Novartis, Roche, Takeda; Financial Interests, Personal, Advisory Board, Lecture fees: AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Takeda, Thermo Fisher. S. Ekman: Financial Interests, Personal, Other, Unrestricted grant for Investigator Initiated Study: Boehringer Ingelheim; Financial Interests, Personal, Other, Non-remunerated Expert Meetings: MSD, BMS, Takeda, AstraZeneca, Amgen, Boenringer Ingelheim . F. Guisier: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, BMS, Janssen, MSD, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi; Financial Interests, Institutional, Research Funding: Pfizer, Roche, Takeda. C. Ho: Financial Interests, Personal, Research Funding: AstraZeneca, Roche; Financial Interests, Other, Honoraria: AbbVie, Amgen, AstraZeneca, Bayer, BMS, CADTH, Eisai, Jazz, Janssen, Merck Healthcare KGaA, Darmstadt, Germany, Novartis, Pfizer, Roche, Sanofi. D. Kazdal: Financial Interests, Personal, Other, Personal fees: Agilent, AstraZeneca, Bristol Myers Squibb, Ilumina, Incyte, Lilly, Pfizer, Takeda. J.B. Kuon: Financial Interests, Personal, Research Grant: AstraZeneca, BMS; Financial Interests, Personal, Other, Speaker honoraria: Takeda, Pfizer, Roche, AstraZeneca, BMS. F. Haglund de Flon: Financial Interests, Personal, Research Funding: Ilumina, Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Other, Honoraria: Roche. A. Stenzinger: Financial Interests, Personal, Advisory Board, Speaker Bureau as well: Aignostics, Amgen, AstraZeneca, Bayer, BMS, Eli Lilly, Ilumina, Incyte, Janssen, MSD, Novartis, Pfizer, Qlucore, Roche, Seagen, Takeda, Thermo Fisher; Financial Interests, Personal, Other, Grants: Bayer, BMS, Chugai, Incyte. A. Hatswell: Financial Interests, Personal, Full or part-time Employment: Delta Hat Limited. T. McLean: Financial Interests, Personal, Full or part-time Employment: Merck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA. S. Bergman: Financial Interests, Personal, Full or part-time Employment: Merck AB, Solna, Sweden, an affiliate of Merck KGaA. K. Orlowski: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare Germany GmbH, Darmstadt, Germany, an affiliate of Merck KGaA. A.M. OBrate Grupp: Financial Interests, Personal, Other, Employee: Merck Healthcare KGaA, Darmstadt, Germany. H. Vioix: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. M. Thomas: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim , Celgene, Chugai, Janssen Oncology, Lilly, Merck Healthcare KGaA, Darmstadt, Germany, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Board, since 2020: BeiGene; Financial Interests, Personal, Advisory Board, Since 2020 : Daiichi Sankyo, GSK, Sanofi ; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Merck Healthcare KGaA, Darmstadt, Germany, Roche, Takeda; Non-Financial Interests, Personal, Other, travel costs: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Lilly, Merck Healthcare KGaA, Darmstadt, Germany, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda. All other authors have declared no conflicts of interest.