Treatment Sequencing and Immunotherapy Rechallenge in Advanced Non-Small-Cell Lung Cancer: Final 24-Month Real-World...

Nivolumab is approved for the treatment of advanced non-small cell lung cancer (aNSCLC) after prior chemotherapy. The Lung Initiative on Sequence Therapy (LIST) study evaluated long-term outcomes, safety and feasibility of immunotherapy rechallenge in French patients with previously treated aNSCLC in routine practice. We report the results of the final 24-month analysis.

LIST was a longitudinal, prospective, observational study enrolling patients with aNSCLC who had received ≥ 1 prior line of therapy and were initiating treatment with nivolumab. Patients were classified into three cohorts according to prior immunotherapy exposure: immunotherapy-naïve (cohort 1); immunotherapy-experienced and discontinued prior immunotherapy for reasons other than immunotherapy-related toxicity (cohort 2); and discontinued because of immunotherapy-related toxicity (cohort 3). The primary endpoint was time to treatment discontinuation (TTD). Secondary endpoints included overall survival (OS), progression-free survival (PFS), response at 24 months, safety and quality of life (QoL).

A total of 522 patients were included (cohort 1, n = 280; cohort 2, n = 197; cohort 3, n = 45). Median TTD was 3.8, 3.2 and 3.4 months in cohorts 1, 2 and 3, respectively, with 24-month discontinuation-free rates of 7.9%, 6.0% and 7.1%. Median OS was 12.3, 9.5 and 9.8 months, and median PFS was 3.2, 2.6 and 3.9 months across cohorts 1, 2 and 3, respectively. Disease progression was the most common reason for nivolumab discontinuation. Numerically higher discontinuation-free rates were observed in patients who were younger (< 75 years), had better performance status, had non-squamous histology, were current smokers or had demonstrated prolonged benefit with prior immunotherapy. Safety outcomes were consistent with the established nivolumab profile, with no new safety signals. Among patients with available data, QoL changes were generally small.

Consistent with results from previous analyses, this final 24-month analysis of LIST demonstrated real-world effectiveness and safety of nivolumab in patients with aNSCLC. Nivolumab rechallenge appears to be an option in selected patients, based on patient and disease characteristics and prior immunotherapy history.

ClinicalTrials.gov identifier NCT04500535.