A retrospective study of tislelizumab combined with bevacizumab, pemetrexed, and carboplatin in driver-gene mutated advanced non-squamous non-small cell lung cancer after tyrosine kinase inhibitors failure.

Abstract

e20620 Background: Overcoming resistance to tumor targeted therapies is a major challenge in the management of driver-gene mutated non-small cell lung cancer (NSCLC). Recent clinical trials suggested that the combination approach of immunotherapy, bevacizumab and platinum-based chemotherapy was effective for driver-gene mutated NSCLC after tyrosine kinase inhibitors (TKIs) failure. Our retrospective study was aimed to examine the efficacy and safety of tislelizumab (TIS) combined with bevacizumab plus chemotherapy for advanced driver-gene mutated non-squamous NSCLC (nsq NSCLC) who had failed to TKIs therapies. Methods: We retrospectively collected medical records of driver-gene mutations advanced nsq NSCLC who had failed to TKIs therapies in the Affiliated Hospital of Zunyi Medical University and Second Affiliated Hospital of Zunyi Medical University from January 2021 to December 2023. The participants were sorted into two groups. Pts in TBCP group received TIS combined with bevacizumab, carboplatin and pemetrexed (BCP) for six cycles, followed by TIS with pemetrexed as maintenance therapy. Pts in BCP group received BCP regimen for six cycles, followed by pemetrexed as maintenance therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: A total of 12 pts were enrolled (6 pts in TBCP group and 6 pts in BCP group). In TBCP group, there was one patient with EGFR exon 19del, KRAS, BRAF V600 mutation and RET fusion, respectively. 2 pts harbored EGFR exon 21 L858R mutations. In BCP group, 4 pts harbored EGFR exon 19del, 1 patient with exon 21 L858R, and 1 patinet with BRAF V600 mutation. All pts were failed to previous TKI therapy. 3 pts (50%) had progression after two systemic treatment lines in ABCP group. 4 pts(66.7%) had progressive disease after at least two systemic regimen. As of 6 February 2024 (median follow-up, 18.6 months), significantly longer PFS was observed in TBCP group compared with BCP group (HR = 0.269 [95% CI: 0.068-1.065], p = 0.0080). Median PFS was 14.20 months (95% CI: 0.5010-5.379) and 8.65 months (95% CI: 0.1859-1.996) in TBCP group and BCP group, respectively. A higher ORR assessed was observed with TBCP group (66.7%) compared with BCP group (33.3%). The DCR were both 100% in two groups. Median OS was not reached. Grade 3-4 TRAEs occurred in 1 and 2 pts in TBCP group and BCP group, respectively. Conclusions: TIS combined with bevacizumab, carboplatin and pemetrexed has shown a promising anti-tumor efficacy with manageable safety profile for TKI failure driver-gene mutations advanced nsq NSCLC. However, these findings still need to be further confirmed by prospective clinical trials with larger sample sizes.