The addition of toripalimab to nab-paclitaxel significantly improves progression-free survival (PFS) in patients with PD-L1-positive metastatic or recurrent triple-negative breast cancer (TNBC), according to results from the TORCHLIGHT trial presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

These findings were presented by lead author Zefei Jiang, MD, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

The phase 3 TORCHLIGHT trial evaluated the efficacy and safety of toripalimab, a monoclonal antibody targeting PD-1, in combination with nab-paclitaxel as a first-line treatment for metastatic or recurrent TNBC. The primary study end point was PFS as assessed by blinded independent central review, first in the PD-L1-positive population and then in the intention-to-treat (ITT) population. Secondary end points included overall survival (OS) and safety.

A total of 531 patients were enrolled in the study and randomized in a 2:1 ratio to receive either toripalimab (n = 353) or placebo (n = 178). Among these, 200 patients in the toripalimab group and 100 patients in the placebo group had PD-L1-positive TNBC. Patients were stratified by PD-L1 expression, prior paclitaxel therapy, and the line of prior therapy.

Interim analysis was conducted with a median follow-up of 14 months. In the PD-L1 positive subgroup, median PFS was 8.4 months with toripalimab vs 5.6 months with placebo (hazard ratio [HR], 0.653, 95% confidence interval [CI], 0.470 to 0.906; P = 0.0102). The trend towards improved PFS was also observed in the ITT population with a median PFS of 8.4 months with toripalimab vs 6.9 months with placebo (HR, 0.773; 95% CI, 0.602 to 0.994).

Descriptive analysis of OS showed a similar trend, with toripalimab demonstrating improved OS in both the PD-L1 positive and ITT populations. The median OS in the PD-L1-positive population was 32.8 months with toripalimab vs 19.5 months with placebo (HR, 0.615; 95% CI, 0.414 to 0.914). Median OS in the ITT population was 33.1 months vs 23.5 months, respectively (HR, 0.691; 95% CI, 0.513 to 0.932).

Regarding safety, no new safety concerns were identified. Grade ≥3 adverse events (AEs) and fatal AEs were similar between the toripalimab and placebo arms. However, AEs leading to discontinuation of toripalimab or placebo and immune-related AEs were more frequent in the toripalimab arm.

In conclusion, the addition of toripalimab to nab-paclitaxel as a first-line treatment for patients with PD-L1-positive metastatic or recurrent TNBC significantly improved PFS. Final analyses of PFS and OS outcomes are still pending, as patients continue to be followed.

Source:

Jiang Z, Ouyang Q, Sun T, et al. TORCHLIGHT: A randomized, double-blind, phase III trial of toripalimab versus placebo, in combination with nab-paclitaxel(nab-P) for patients with metastatic or recurrent triple-negative breast cancer (TNBC). Presented at the ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract LBA1013