13P Tislelizumab (TIS) plus chemotherapy (chemo) with or without bevacizumab (beva) for patients with EGFR-mutated nonsquamous non-small cell lung cancer (nsq-NSCLC) after progression on EGFR tyrosine kinase inhibitor (TKI) therapy

This multicenter, open-label, phase II study evaluated TIS plus platinum-based chemo (cohort 1) or TIS plus mono-chemo and beva (cohort 2) in EGFR-mutated nsq-NSCLC patients (pts) who progressed on EGFR-TKI therapies. Our previous results showed that cohort 1 met its primary endpoint (1-year PFS rate, 23.8%). Here, we reported the primary analysis results of cohort 2 and updated results of cohort 1. In cohort 2, pts received TIS plus nab-paclitaxel and beva (induction), followed by TIS plus beva (maintenance). Primary endpoint was 1-year PFS rate; we planned to enroll 54 pts (85% power to detect an increase from historical control of 7% to 23% at a one-side 0.05 significance level). Updated efficacy analysis was provided for cohort 1. For cohort 2 (median follow-up:10.5 months mo), 54 pts were enrolled. Among 52 pts in efficacy analysis set, 1-year PFS rate was 46.1% (90% CI 32.5-58.7), which met the primary endpoint. Median PFS was 10.9 (95% CI 6.4-15.1) mo. The ORR and DCR were 55.8% (95% CI 41.3-69.5) and 96.2% (95% CI 86.8-99.5), respectively. Grade 3-4 TRAEs occurred in 31.5% (17/54) of pts. 38.9% (21/54) of pts experienced irAEs. For cohort 1 (median follow-up: 20.4 mo), median PFS and OS were 7.6 (95% CI 5.8-9.4) mo and 27.1 (95% CI 16.1-NE) mo, respectively. Pts with EGFR exon 19 deletion or progressed on 1st/2nd and 3rd generation (G) EGFR-TKIs have significant shorter PFS compared to pts with EGFR exon 21 L858R mutation or progressed on 1st/2nd G EGFR-TKIs in cohort 1; while no significant differences were observed in cohort 2 (Table). Table: 13PSubgroup analysis of PFS by cohortCohort 1Cohort 2Median PFS (mo)HR (95% CI)PMedian PFS (mo)HR (95% CI)POverall7.6//10.9//Prior EGFR mutation typeExon 21 L858R mutation11.70.33 (0.17, 0.63)<0.00110.91.37 (0.61,3.09)0.438Exon 19 deletion6.514.8Prior EGFR TKI treatment1st/2nd+3rd G6.01.83 (1.00,3.36)0.0496.72.18 (0.77,6.23)0.1363rd G5.71.21 (0.44, 3.27)0.72614.81.18 (0.39, 3.54)0.7671st/2nd G9.814.2PFS, progression-free survival; mo, months; HR, hazard ratio; CI, confidence interval; G, generation; NE, not estimable. Open table in a new tab PFS, progression-free survival; mo, months; HR, hazard ratio; CI, confidence interval; G, generation; NE, not estimable. For pts with EGFR-mutated nsq-NSCLC after EGFR-TKI failure, TIS plus mono-chemo and beva (cohort 2) was effective with favorable safety profile; TIS plus platinum-based chemo (cohort 1) demonstrated encouraging OS benefit. This study provides extended treatment options for this patient population.