Abstract 54P
Background
METΔ14ex is the driver alteration for approximately 3% of non-small cell lung cancers (NSCLC) and associated with a higher PD-L1 expression, but unclear benefit from immunotherapy (IO).
Methods
Seventy-eight consecutive patients with metastatic NSCLC harboring METΔex14 who received first-line IO as monotherapy or chemoimmunotherapy (CHT+IO) in 10 German academic lung cancer centers were analyzed.
Results
The median age was 72 years (range 49-86), 34 patients (44%) were female, 47 (60%) were active or former smokers, and 23 (29%) presented with brain metastases. The Eastern Cooperative Group (ECOG) performance status was 0, 1, 2 and 3 in 27 (35%), 28 (36%), 18 (23%) and 4 (5%) cases, respectively. The most common histology was adenocarcinoma (n=61, 78%). IO was given to 43 (55%) patients as monotherapy, and to 35 (45%) combined with CHT. For patients with PD-L1 tumor proportion score (TPS) ≥50% (n=52, 67%), 1-49% (n=14, 18%) and <1% (n=12, 15%), disease control rates (DCR) were 56%, 57% and 100% (p=0.015), respectively. Other efficacy parameters including overall response rate (ORR), median progression-free survival (mPFS) and median overall survival (mOS) by PD-L1 tumor proportion score (TPS) and type of treatment are summarized in the table. Primary progressive disease/early death (before radiologic reassessment) under IO monotherapy, but not under CHT+IO, was significantly associated with never-smoker status (p=0.041). No significant correlations were found between smoking status and PD-L1 TPS (p=0.595).
Table: 54P
| TPS≥50% / IO n=43 | TPS≥50% / CHT+IO n=9 | TPS 1-49% / CHT+IO n=14 | TPS 0% / CHT+IO n=12 | p-value | |
| ORR (%) | 35 | 56 | 43 | 50 | 0.599 |
| DCR (%) | 54 | 67 | 57 | 100 | 0.030 |
| mPFS (mo) | 3 | 4 | 6 | 15 | 0.520 |
| mOS (mo) | 14 | 5 | 15 | 16 | 0.690 |
Conclusions
Our exploratory analysis suggests an association between higher PD-L1 TPS and worse clinical outcomes under IO in patients with NSCLC harboring METΔ14ex. Although these results should be interpreted with caution, they contrast the favorable effect of PD-L1 expression for IO efficacy in other NSCLC and underline the need for alternative biomarkers for IO in this patient population.
Legal entity responsible for the study
Thoraxklinik Heidelberg.
Funding
Deutsches Zentrum für Lungenforschung; Merck.
Disclosure
J.B. Kuon: Financial Interests, Personal, Invited Speaker: BMS, AstraZeneca, Pfizer. D. Misch: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Novartis, Roche, Sanofi, Takeda. D. Kauffmann-Guerrero: Financial Interests, Personal, Advisory Board: BMS, Boehringer Ingelheim, MSD, Roche, Pfizer, AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Other: Novartis. M. Hilbrandt: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. B. Hackanson: Financial Interests, Personal, Invited Speaker: BMS, MSD, Boehringer Ingelheim, Pfizer, Roche, AstraZeneca. M. Faehling: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, MSD; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, Gilead, Roche, Daiichi Sankyo, Mirati, Revolution Medicines. M. Kirchner: Financial Interests, Personal, Invited Speaker: Veracyte Inc. M. Allgäuer: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. C. Grohe: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Takeda, MSD, Novartis, Pfizer, Roche, AbbVie, Tesaro/GSK, Blueprint Medicines. A. Tufman: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Daiichi Sankyo, AstraZeneca, Roche, Pfizer, BMS, MSD, Sanofi, Lilly, Novartis. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo. N. Frost: Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, BeiGene, Berlinchemie, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Merck Sharp&Dohme, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda. A. Stenzinger: Financial Interests, Personal, Advisory Board: Aignostics, AstraZeneca, Janssen, Bayer, Seattle Genetics, Pfizer, MSD, Eli Lilly, Illumina, Thermo Fisher, Amgen; Financial Interests, Institutional, Advisory Board: BMS, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: Roche, Incyte; Financial Interests, Institutional, Research Grant: Bayer, Chugai, BMS, Incyte. M. Thomas: Financial Interests, Personal, Advisory Board: Sanofi, Lilly, BMS, MSD, Roche, Boehringer, Janssen, AstraZeneca, Amgen, Novartis; Financial Interests, Personal, Invited Speaker: Sanofi, Lilly, MSD, Roche, GSK, Pfizer, Janssen, AstraZeneca, Amgen, Novartis; Financial Interests, Institutional, Advisory Board: Takeda; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Funding: Roche, Takeda, BMS, AstraZeneca, Amgen. P. Christopoulos: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, MSD, Takeda, Roche, Daiichi Sankyo; Financial Interests, Personal, Expert Testimony: Chugai; Financial Interests, Personal, Invited Speaker: Gilead, Thermo Fisher; Financial Interests, Institutional, Funding: AstraZeneca, Boehringer Ingelheim, Amgen, Novartis, Roche; Financial Interests, Personal, Funding: Takeda. All other authors have declared no conflicts of interest.