In a significant advancement in cancer research, Dr. Zefei Jiang and his team from The Fifth Medical Center of  Chinese PLA General Hospital published the article "Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial" in Nature Medicine(IF=83) on January 1, 2024. This pivotal study investigates the efficacy and safety of combining toripalimab, an immune checkpoint inhibitor, with nab-paclitaxel in treating metastatic or recurrent triple-negative breast cancer (TNBC). TNBC, marked by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, presents limited treatment options and a poor prognosis. The study addresses the urgent need for more effective therapies for this aggressive breast cancer subtype.

The TORCHLIGHT trial enrolled 531 women with metastatic or recurrent TNBC from 54 centers, randomized in a 2:1 ratio to receive either toripalimab plus nab-paclitaxel (353 patients) or placebo plus nab-paclitaxel (178 patients). The study population included 300 patients with PD-L1-positive TNBC.

Key findings from the study include:

• Progression-Free Survival (PFS): In the PD-L1-positive population, the median PFS was 8.4 months in the toripalimab group compared to 5.6 months in the placebo group (HR 0.65; 95% CI 0.470–0.906; P=0.0102). In the intention-to-treat (ITT) population, the median PFS was 8.4 months for the toripalimab group versus 6.9 months for the placebo group (HR 0.77; 95% CI 0.602–0.994; P=0.0445).
• Overall Survival (OS): The median OS was significantly improved in the toripalimab group, with 32.8 months in the PD-L1-positive population versus 19.5 months in the placebo group (HR 0.62; 95% CI 0.414–0.914; P=0.0148). In the ITT population, the median OS was 33.1 months for the toripalimab group compared to 23.5 months for the placebo group (HR 0.69; 95% CI 0.513–0.932; P=0.0145).
• Safety: The incidence of treatment-emergent adverse events (TEAEs) was similar between the two groups, with 99.2% in the toripalimab group and 98.9% in the placebo group. Grade ≥3 TEAEs occurred in 56.4% of the toripalimab group compared to 54.3% of the placebo group. Serious adverse events (SAEs) were more frequent in the toripalimab group (27.2% vs. 17.1%), but the overall safety profile was considered acceptable.

Results

The trial’s results demonstrated the efficacy and safety of the toripalimab plus nab-paclitaxel regimen:

（Nat Med. 2024 Jan ;30(1): 249-256. doi:10.1038/s41591-023-02677-x.）

• Progression-Free Survival (PFS): In the PD-L1-positive subgroup, the median PFS was 8.4 months in the toripalimab group versus 5.6 months in the placebo group, with a hazard ratio (HR) of 0.65 (95% CI 0.470–0.906; P=0.0102). In the intention-to-treat (ITT) population, the median PFS was 8.4 months for the toripalimab group compared to 6.9 months for the placebo group (HR 0.77; 95% CI 0.602–0.994; P=0.0445).
• Overall Survival (OS): The median OS in the PD-L1-positive population was significantly better in the toripalimab group at 32.8 months, compared to 19.5 months in the placebo group (HR 0.62; 95% CI 0.414–0.914; P=0.0148). For the ITT population, the median OS was 33.1 months in the toripalimab group versus 23.5 months in the placebo group (HR 0.69; 95% CI 0.513–0.932; P=0.0145).
• Objective Response Rate (ORR): The ORR was similar between the two groups, with 66.0% in the toripalimab group and 68.0% in the placebo group for the PD-L1-positive population, and 64.3% versus 64.0% in the ITT population. However, the duration of response (DoR) was significantly longer in the toripalimab group, with a median DoR of 10.8 months compared to 5.6 months in the placebo group (HR 0.55; 95% CI 0.366–0.830; P=0.0040) for the PD-L1-positive subgroup, and 8.5 months versus 6.9 months in the ITT population (HR 0.64; 95% CI 0.468–0.881; P=0.0060).
• Safety: Treatment-emergent adverse events (TEAEs) occurred in 99.2% of patients in the toripalimab group and 98.9% in the placebo group. Grade ≥3 TEAEs were observed in 56.4% of the toripalimab group and 54.3% of the placebo group. Serious adverse events (SAEs) were more frequent in the toripalimab group (27.2% vs. 17.1%). The primary TEAEs included hypothyroidism, nausea, and asthenia. The immune-related adverse events (irAEs) were also higher in the toripalimab group, including hypothyroidism (13.3% vs. 4.0%), rash (9.3% vs. 8.6%), and hyperthyroidism (7.1% vs. 1.1%).

The study’s significance lies in demonstrating that the addition of toripalimab to nab-paclitaxel significantly improves PFS and OS in patients with PD-L1-positive metastatic or recurrent TNBC. This combination therapy provides a promising new treatment option for this challenging cancer subtype, addressing a critical unmet need and offering hope for improved patient outcomes.

Conclusion

The TORCHLIGHT trial provides compelling evidence supporting the use of toripalimab plus nab-paclitaxel as a first-line treatment for metastatic or recurrent triple-negative breast cancer. The significant improvements in progression-free and overall survival highlight the potential of this combination therapy to enhance patient outcomes. These findings are pivotal in shaping future treatment protocols for TNBC, emphasizing the importance of integrating immune checkpoint inhibitors with chemotherapy. This study underscores the need for further research to optimize treatment strategies and validate these results in broader populations