Analyzing Advanced Triple-Negative Breast Cancer With Pembrolizumab and Chemotherapy

Apreliminary examination of the phase 3 trial, including pembrolizumab alongside chemotherapy, demonstrated a prolonged period without disease progression compared to chemotherapy alone in individuals with advanced triple-negative breast cancer. This benefit was explicitly observed in patients whose tumors exhibited the presence of programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of 10 or higher. The CPS is calculated by dividing the number of PD-L1-staining tumor cells, lymphocytes, and macrophages by the total number of viable tumor cells and multiplying the result by 100.

Patients diagnosed with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer were randomly assigned in a 2:1 ratio. The assigned treatment consisted of pembrolizumab at a dosage of 200 mg administered every 3 weeks, in combination with the chemotherapy regimen chosen by the investigator (nanoparticle albumin-bound paclitaxel, paclitaxel, or gemcitabine-carboplatin).

In contrast, the control group received a placebo and the same chemotherapy regimen. The main objectives of the study was to assess progression-free survival (previously reported) and overall survival in three specific patient subgroups: those with tumors expressing PD-L1 with a CPS of 10 or higher (referred to as the CPS-10 subgroup), those with tumors expressing PD-L1 with a CPS of 1 or higher (referred to as the CPS-1 subgroup), and the entire intention-to-treat population. Additionally, an evaluation of safety was conducted. A cohort comprising 847 individuals was subjected to randomization, with 566 individuals being allocated to the pembrolizumab-chemotherapy group and 281 individuals assigned to the placebo-chemotherapy group. The duration of the median follow-up period was 44.1 months. In the CPS-10 subgroup, the pembrolizumab-chemotherapy group exhibited a median overall survival of 23.0 months, while the placebo-chemotherapy group had a median survival of 16.1 months. The hazard ratio for death was 0.73, with a 95% CI of 0.55 to 0.95. The two-sided P= 0.0185 meets the criterion for significance. In the CPS-1 subgroup, the median overall survival was 17.6 months in the pembrolizumab-chemotherapy group and 16.0 months in the placebo-chemotherapy group. The hazard ratio was 0.86, with a 95% CI of 0.72 to 1.04.

The two-sided P= 0.1125 indicated that the results were not statistically significant. In the intention-to-treat population, the median overall survival was 17.2 months in the pembrolizumab-chemotherapy group and 15.5 months in the placebo-chemotherapy group. The hazard ratio was 0.89, with a 95% CI of 0.76 to 1.05. The significance of these results was not tested. Many patients in the pembrolizumab-chemotherapy group (68.1%) and the placebo-chemotherapy group (66.9%) experienced grade 3, 4, or 5 adverse events associated with the trial regimen. Notably, mortality occurred in 0.4% of patients in the pembrolizumab-chemotherapy group, while no deaths were reported in the placebo-chemotherapy group. In the cohort of individuals diagnosed with advanced triple-negative breast cancer, whose tumors exhibited PD-L1 expression with a Combined Positive Score of 10 or higher, the inclusion of pembrolizumab alongside chemotherapy yielded a notable extension in overall survival when compared to the administration of chemotherapy as a standalone treatment.

Source: https://pubmed.ncbi.nlm.nih.gov/35857659/

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02819518

Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Perez-Garcia J, Iwata H, Masuda N, Torregroza Otero M, Gokmen E, Loi S, Guo Z, Zhou X, Karantza V, Pan W, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022 Jul 21;387(3):217-226. doi: 10.1056/NEJMoa2202809. PMID: 35857659.