Pembrolizumab plus chemotherapy significantly improves survival in advanced triple-negative breast cancer expressing programmed death ligand 1, with a combined positive score of 10 or more compared to chemotherapy alone, according to a phase 3 trial.
Triple-negative breast cancer (TNBC) lacks the expression of estrogen and progesterone receptors and involves overexpression of human epidermal growth factor receptor 2. Pembrolizumab monotherapy has durable anti-tumor activity in advanced TNBC, particularly among patients with higher programmed death ligand 1 (PD-L1) expression.
A study in The New England Journal of Medicine examined whether the addition of pembrolizumab would improve the anti-tumor activity of chemotherapy in patients with previously untreated inoperable or metastatic TNBC.
Study Population
A total of 847 patients were included and randomized to the pembrolizumab–chemotherapy group (n=566) or placebo–chemotherapy group (n=281). At the data-cutoff point, the median time since randomization was 44.1 months. The baseline characteristics were well-balanced between the groups. The median duration of exposure was 26.4 and 23.1 weeks in the pembrolizumab–chemotherapy and placebo–chemotherapy groups, respectively.
Pembrolizumab Boosts Overall Survival in Advanced Cancer Patients
In the combined positive score (CPS) of 10 or more (CPS-10) subgroups, 70.5% of patients in the pembrolizumab–chemotherapy group and 81.6% of patients in the placebo–chemotherapy group died. The median overall survival was 23 months in the pembrolizumab–chemotherapy group and 16.1 months in the placebo–chemotherapy group (p=0.0185).
Survival Disparity in CPS-10 Subgroup With Pembrolizumab vs. Placebo
The final analysis showed that adding pembrolizumab to chemotherapy resulted in statistically significant longer overall survival than chemotherapy alone. No significant between-group difference was observed in overall survival in the CPS of 1 or more (CPS-1) subgroups. In the intention-to-treat population, the median overall survival was 17.2 and 15.5 months, respectively (significance not tested). The improvement in overall survival with pembrolizumab increased with higher PD-L1 expression at a threshold of CPS 10 or more, with similar benefits observed with a CPS of 10 or more and a CPS of 20 or more.
Pembrolizumab–Chemotherapy Group Demonstrated Longer Progression-Free Survival The median progression-free survival (PFS) in the pembrolizumab–chemotherapy group was 9.7 months and 5.6 months in the placebo–chemotherapy (hazard ratio (HR): 0.66) in the CPS-10 subgroup, 7.6 vs. 5.6 months (HR: 0.75) in the CPS-1 subgroup, and 7.5 vs. 5.6 months (HR: 0.82) in the intention-to-treat population.
Pembrolizumab Combination Yielded Higher Tumor Response Rates
A confirmed objective tumor response occurred in 52.7% vs. 40.8% (CPS-10 subgroup), 44.9% vs. 38.9% (CPS-1 subgroup), and 40.8% vs. 37% (intention-to-treat population) of patients in the pembrolizumab–chemotherapy vs. placebo–chemotherapy groups, respectively. Moreover, the duration of tumor response was longer in the pembrolizumab–chemotherapy group than in the placebo–chemotherapy group.
Adverse Events of the Pembrolizumab-Chemotherapy Combination
Treatment-related adverse events occurred in 96.3% and 95% of patients in the pembrolizumab–chemotherapy group and placebo–chemotherapy group, respectively. Treatment-related adverse events of grade 3 or higher occurred in 68.1% and 66.9% of the patients in the two groups, respectively, with death occurring in 0.4% of patients in the pembrolizumab–chemotherapy group and in no patients in the placebo–chemotherapy group. Immune-mediated adverse events occurred in 26.5% and 6.4% of the patients in the two groups, respectively, but did not cause death.
Source
Cortés, J., Rugo, H. S., Cescon, D. W., Im, S., Yusof, M. M., Gallardo, C., Lipatov, O., Barrios, C. H., Pérez-García, J. M., Iwata, H., Masuda, N., Otero, M. T., Erhan, G., Sherene, L., Guo, Z., Zhou, X., Karantza, V., Pan, W., & Schmid, P. (2022). Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. The New England Journal of Medicine, 387(3), 217–226. https://doi.org/10.1056/nejmoa2202809
