Abstract 13P
Background
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.
Methods
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.
Results
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: 13P
Subgroup analysis of PFS by cohort
| Cohort 1 | Cohort 2 | |||||
| Median PFS (mo) | HR (95% CI) | P | Median PFS (mo) | HR (95% CI) | P | |
| Overall | 7.6 | / | / | 10.9 | / | / |
| Prior EGFR mutation type | ||||||
| Exon 21 L858R mutation | 11.7 | 0.33 (0.17, 0.63) | <0.001 | 10.9 | 1.37 (0.61,3.09) | 0.438 |
| Exon 19 deletion | 6.5 | 14.8 | ||||
| Prior EGFR TKI treatment | ||||||
| 1st/2nd+3rd G | 6.0 | 1.83 (1.00,3.36) | 0.049 | 6.7 | 2.18 (0.77,6.23) | 0.136 |
| 3rd G | 5.7 | 1.21 (0.44, 3.27) | 0.726 | 14.8 | 1.18 (0.39, 3.54) | 0.767 |
| 1st/2nd G | 9.8 | 14.2 | ||||
PFS, progression-free survival; mo, months; HR, hazard ratio; CI, confidence interval; G, generation; NE, not estimable.
Conclusions
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.
Clinical trial identification
NCT04405674.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.