TNBC patients benefit from pembrolizumab in combination with various chemotherapies
medwireNews: Beneficial outcomes with pembrolizumab plus chemotherapy persist with different types of chemotherapy in patients with previously untreated, locally recurrent, inoperable, or metastatic triple-negative breast cancer (TNBC), exploratory analysis of the KEYNOTE-355 trial suggests.
The presenting author told delegates of the 2020 San Antonio Breast Cancer Symposium that the addition of pembrolizumab to chemotherapy, regardless of which chemotherapy partner was chosen, particularly benefited PD-L1 enriched patients.
These results expand upon the prespecified interim analysis of the previously reported phase 3 trial, which showed that the addition of pembrolizumab to chemotherapy significantly reduced the risk for disease progression or death by 35% among patients with a combined positive score (CPS) for PD-L1 expression of 10 or more.
In total, 847 patients were randomly assigned to receive pembrolizumab 200 mg every 3 weeks or placebo alongside investigators’ choice of chemotherapy from nab-paclitaxel 100 mg/m2 or paclitaxel 90 mg/m2 on days 1, 8, and 15 of a 28-day cycle or gemcitabine 1000 mg/m2 with carboplatin AUC 2 on days 1 and 8 of a 21-day cycle.
In the intention-to-treat (ITT) population, the median progression-free survival (PFS) in the pembrolizumab and placebo groups was 7.5 versus 5.4 months when given with nab-paclitaxel, 8.0 versus 3.8 months with paclitaxel, and 7.4 versus 7.4 months with gemcitabine–carboplatin. The hazard ratios (HRs) favored pembrolizumab over placebo, at a significant 0.69 and 0.57 for the two taxanes, respectively, and a nonsignificant 0.93 for gemcitabine plus carboplatin.
When stratified by PD-L1 expression, patients with a CPS of at least 1 or at least 10 also had longer PFS if given pembrolizumab rather than placebo alongside chemotherapy.
“Interestingly, [pembrolizumab] treatment effects increased with PD-L1 enrichment,” Hope Rugo (University of California San Francisco Comprehensive Cancer Center, USA) explained.
Indeed, among patients with a CPS of at least 10, median PFS in the pembrolizumab group was 9.9, 9.6, and 8.0 months with nab-paclitaxel, paclitaxel, and gemcitabine–carboplatin, respectively, versus 5.5, 3.6, and 7.2 months in the placebo group, giving corresponding HRs of 0.57, 0.33, and 0.77, the first two of which were significant.
Similarly, pembrolizumab was associated with a significant improvement in median PFS among patients with a CPS of 1 or more who received nab-paclitaxel or paclitaxel, at 6.3 versus 5.3 months and 9.4 versus 3.8 months, respectively (HRs=0.66 and 0.46). But again the difference between the pembrolizumab and placebo arms was not significant for those given gemcitabine–carboplatin, at an identical median of 7.5 months in both arms and a nonsignificant HR of 0.86.
But she noted that “although subgroup analyses by on-study [chemotherapy] were prespecified, the trial was not powered to compare efficacy among treatment groups by different [chemotherapy regimens.”
Patients given pembrolizumab also had better objective response rates, disease control rates, and duration of responses than patients who received placebo. Rugo noted that for these secondary endpoints there was also a trend toward increased benefit from the pembrolizumab–chemotherapy combination with PD-L1 enrichment.
Overall, Rugo concluded that these findings “further support a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic TNBC.”
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