Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis.

Objective: This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC).

Methods: NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared.

Results: Of 57 study subjects, 63.2% received third- and later-line therapy, with median progression-free survival (mPFS) of 4 months, overall response rate (ORR) of 10.5%, and disease control rate (DCR) of 80.7%. The incidence of therapy-related adverse events was 42.1%, and there was only one case presenting grades 3 and 4 adverse events (1.8%). Among driver gene-negative participants, vinorelbine combination therapy regimens achieved longer mPFS (4.6 vs. 1.2 months, hazards ratio = 0.11, P < 0.0001) and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine combined with immune checkpoint inhibitors showed the highest response, with mPFS of 5.6 months (95% CI 4.8 to 6.4 months), ORR of 25%, and DCR of 81.3%. Among participants with gradual resistance to osimertinib, continuing osimertinib in combination with metronomic oral vinorelbine achieved mPFS of 6.3 months (95% CI 0.1 to 12.5 months) and DCR of 86.7%.

Conclusion: Metronomic oral vinorelbine and its combination therapy regimens are favorable options as second- and later-line therapy for advanced NSCLC patients, with acceptable efficacy and tolerable toxicity. Vinorelbine combination therapy regimens show higher efficacy and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine may have a synergistic effect with immunotherapy and EGFR-TKI targeted therapy.