1326P - Clinical and genomic characteristics of advanced non-small cell lung cancer (aNSCLC) patients (pts) with long-term response to first-line (1L) immunotherapy: A real-world study

Background

Immune checkpoint inhibitors (ICIs), alone or combined with chemotherapy, have been shown to be more efficacious than chemotherapy in 1L treatment of aNSCLC. We aimed to examine clinical and genomic sequencing data of patients with aNSCLC, who had no progression of disease for at least two years since the start of 1L ICIs.

Methods

Working databases of five Israeli cancer centers were searched for cases of aNSCLC pts who commenced 1L treatment with ICIs between 2018-2021, and had no progression of disease for at least two years since the start of 1L ICI treatment. Data collected of identified pts included sex, age, ECOG-PS, histology, genomic sequencing results (performed as part of standard of care), response, progression free survival (PFS) according to treating physicians' assessments and overall survival (OS) by death dates. End of two years from initiation of 1L ICI was the index date. Time to event data was calculated by Kaplan-Meier method. Data cut-off was at November 2023.

Results

209 pts fit the inclusion criteria. Median age was 65y (range 33 - 90); males were 64.6%; never smokers 6.2%; ECOG PS 0/1/2-4 28.7%/61.4%/9.9%; weight loss>5% of body weight within six months prior to diagnosis 17.2%; baseline liver/brain metastasis was reported in 4.8%/22.0%; oligometastatic disease in 80.9%; PDL1 <1%/1-49%/≥50% 18.0%/16.6%/61.1%; KRAS mutation 24.4%; TP53 mutation 22.5%; STK11/KEAP1/both 3.8%/0.5%/0%. Objective response rate (ORR) to 1L ICI was 91% (95% CI: 86%-94%); Median follow-up was 25.0 m (95% CI: 24.0-29.0 m); median PFS 24.5 m (95% CI: 20.5-29.0 m); median OS 28.8 m (95% CI: 26.0-31.8 m) - all from the index date. 58 pts (28% of the cohort; 95% CI: 22-34%) progressed after the index date. Median PFS for these pts was 13.0 m (95% CI: 10.0-19.0 m). Of these, 27 were rechallenged with ICI. ORR to rechallenge was 44% (95% CI: 25%-65%).

Conclusions

In real-life setting, aNSCLC long-term responders to 1L ICI have high rates of oligometastatic disease and high PDL1 expression, and low rates of never-smoking history, baseline liver metastasis and STK11/KEAP1 mutations. Response to rechallenge is similar to previously reported data.

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Daher: Non-Financial Interests, Personal and Institutional, Local PI: Merck Sharp & Dohme; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, Bristol Myers Squibb, Roche. W. Shalata: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, Bristol Myers Squibb. A. Zer, D. Urban, H. Gantz Sorotsky: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, Bristol Myers Squibb, Roche. A. Yaakobson: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, Bristol Myers Squibb; Non-Financial Interests, Personal and Institutional, Local PI: Merck Sharp & Dohme, Bristol Myers Squibb. S. Shamai: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Roche. T. Shentzer Kutiel: Non-Financial Interests, Personal and Institutional, Local PI: Merck Sharp & Dohme; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme. M.T. Moskovitz: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, Bristol Myers Squibb, Roche; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Roche. J. Bar: Financial Interests, Personal, Advisory Board: MSD, Takeda, Roche, Pfizer, AbbVie, Bayer, AstraZeneca, Merck-Serono, J-C healthcare, Medison Pharma, Amgen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Other, Steering committee: AbbVie, Merck Healthcare KGaA, Roche, AstraZeneca; Financial Interests, Institutional, Local PI: MSD, Roche, Takeda, AbbVie; Financial Interests, Institutional, Other, local sub-investigator: Novartis; Financial Interests, Institutional, Research Grant: OncoHost, ImmuneAI, AstraZeneca; Non-Financial Interests, Other, Committee member: IASLC. All other authors have declared no conflicts of interest.