Pts with NSCLC and MET exon 14 skipping (METex14; 3–4%) or MET amplification (METamp; 1–2%) have not been well characterized; this study aimed to address this gap.
This non-interventional descriptive cohort study used real-world data extracted from electronic medical records from academic oncology centers in Israel, The Netherlands, Taiwan, and the USA. Pts had confirmed diagnosis of advanced (stage IIIB–IV) NSCLC (date of diagnosis=index date) between 1 Jan 2010 and 30 Sept 2018 and MET alterations. Medical history was assessed prior to and at the index date (baseline period) and outcomes from first date of treatment to death, loss to follow-up, or end of the study period.
70 pts had METex14 tumors and 47 pts had METamp tumors; testing methods were heterogenous. Concomitant oncogenic mutations were more common in METamp than METex14 pts; 9% of METex14 pts had concomitant METamp. Records of systemic therapy for advanced disease were available for 58 (83%) pts in the METex14 cohort and 36 (77%) pts in the METamp cohort. Common treatments (METex14 vs METamp) were platinum-based therapy (1st line [1L], 44 vs 41%; 2nd line [2L], 35 vs 30%) and MET inhibitor monotherapy (1L, 33 vs 29%; 2L, 30 vs 39%). Immune checkpoint inhibitors (±chemotherapy) were used across 1L (13 vs 16%) and 2L (35 vs 13%). Median (95% CI) time to next treatment or death was 6.3 months (4.8, 10.9) for 1L (n=52) and 7.8 months (3.9, 11.3) for 2L (n=23) in the METex14 cohort and 9.0 months (6.1, 11.7) for 1L (n=34) and 5.1 months (3.3, 12.8) for 2L (n=23) in the METamp cohort. Median (95% CI) overall survival from start of 1L therapy (any) was 12.0 months (6.8, 19.2) in METex14 and 22.0 months (9.8, 31.2) in the METamp cohort Patient records were from Israel (n=18), The Netherlands (n=13), Taiwan (n=23), and the USA (n=63). *Data on brain metastases were available for 52 pts in the METex14 cohort and 28 pts in the METamp cohort.
METex14 (n=70) METamp (n=47) Biopsy method; liquid/tissue 81%/20% 77%/26% Age, median (range); years 74 (37, 92) 63 (37, 87) Gender, male 51% 68% Race: White Asian Other 59% 34% 7% 85% 4% 11% Smoking history (ever smokers) 49% 79% Advanced disease at diagnosis 83% 65% Histology: Adenocarcinoma squamous cell carcinoma sarcomatoid 84% 1% 6% 82% 4% 2% Brain metastases* 19% 25% Comorbidity: Uncomplicated diabetes peripheral vascular disease chronic obstructive pulmonary disease 10% 9% 9% 6% 2% 13%
Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in pts with METex14 who were older and had more advanced disease at diagnosis. Screening for these alterations in pts with advanced NSCLC is warranted.
Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Syneos Health, London, UK.
Merck KGaA, Darmstadt, Germany.
Merck KGaA, Darmstadt, Germany.
J.C-H. Yang: Advisory/Consultancy, personal fees: Boehringer Ingelheim; Advisory/Consultancy, personal fees: Eli Lilly; Advisory/Consultancy, personal fees: Bayer; Advisory/Consultancy, personal fees: Roche/Genentech; Advisory/Consultancy, personal fees: Chugai Pharmaceutical; Advisory/Consultancy, personal fees: MSD; Advisory/Consultancy, personal fees: Pfizer; Advisory/Consultancy, personal fees: Novartis; Advisory/Consultancy, personal fees: BMS; Advisory/Consultancy, personal fees: Ono Pharmaceuticals; Advisory/Consultancy, personal fees: AstraZeneca; Advisory/Consultancy, personal fees: ACT Genomics; Advisory/Consultancy, personal fees: Merck Serono; Advisory/Consultancy, personal fees: Celgene; Advisory/Consultancy, personal fees: Yuhan Pharmaceuticals; Advisory/Consultancy, personal fees: Daiichi Sankyo; Advisory/Consultancy, personal fees: Hansoh Pharmaceuticals; Advisory/Consultancy, personal fees: Takeda Pharmaceuticals; Advisory/Consultancy, personal fees: Blueprint Medicines; Advisory/Consultancy, personal fees: Amgen. J-Y. Shih: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Chugai Takeda; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb. N. Peled: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Foundation Medicine; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Gaurdant360; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): NovellusDx; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Takeda. E. Smit: Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Takeda; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Seattle Genetics. R. Camidge: Advisory/Consultancy: Anchiarno; Advisory/Consultancy: Amgen; Advisory/Consultancy, Leadership role, Research grant/Funding (self), Principle investigator for company sponsored trials (institution): Takeda; Advisory/Consultancy: Roche; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Pfizer; Advisory/Consultancy: CBT Pharmaceuticals; Advisory/Consultancy, Interstitial Lung Disease adjudication committee: Daiichi-Sankyo; Advisory/Consultancy, data safety monitoring board: G1 Therapeutics; Advisory/Consultancy, data safety monitoring board: Bio-Thera; Advisory/Consultancy: Blueprint; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Abbvie; Advisory/Consultancy: Achilles; Advisory/Consultancy: BeyondSpring; Advisory/Consultancy, standing Scientific Review Committee: Apollomics; Advisory/Consultancy, standing Scientific Review Committee: 14ner/Elevation; Advisory/Consultancy: Archer; Advisory/Consultancy: Helssin; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Bristol-Myers Squibb; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Medtronic; Advisory/Consultancy: Ribon; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): AstraZeneca; Advisory/Consultancy: Arrys/Kyn; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Hengrui; Advisory/Consultancy, Scientific Review Committee and Principle investigator for company sponsored trials (institution): Hansoh; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Roche/Genentech; Advisory/Consultancy: Inivata; Leadership role, Principle investigator for company sponsored trials (institution): GlaxoSmithKline; Leadership role, Principle investigator for company sponsored trials (institution): Inhibrx; Leadership role, Principle investigator for company sponsored trials (institution): Lycera; Leadership role, Principle investigator for company sponsored trials (institution): MedImmune; Leadership role, Principle investigator for company sponsored trials (institution): Merck; Leadership role, Principle investigator for company sponsored trials (institution): Pfizer; Leadership role, Principle investigator for company sponsored trials (institution): Phosplatin; Leadership role, Principle investigator for company sponsored trials (institution): Psioxus; Leadership role, Principle investigator for company sponsored trials (institution): Rain; Leadership role, Principle investigator for company sponsored trials (institution): Seattle Genetics; Leadership role, Principle investigator for company sponsored trials (institution): Symphogen; Leadership role, Principle investigator for company sponsored trials (institution): Tolero. D. Carbone: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Nexus Oncology; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bayer; Advisory/Consultancy: Biothera; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Helsinn Therapeutics; Advisory/Consultancy: Incyte; Advisory/Consultancy: Inivata; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Peregrine Pharmaceuticals; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Synta. D. Oksen, E. Boutmy, A. Johne: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. P. Paik: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Calithera; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Lilly; Advisory/Consultancy: Takeda; Research grant/Funding (self), Research grant/Funding (institution): EMD Serono. All other authors have declared no conflicts of interest.