Pembrolizumab plus chemotherapy extends PFS in breast cancer subset
The addition of pembrolizumab to various chemotherapy partners improved PFS among certain patients with inoperable or metastatic triple-negative breast cancer, according to study results presented at ASCO20 Virtual Scientific Program.
Results of the randomized phase 3 KEYNOTE-355 trial — which included patients with previously untreated, locally recurrent inoperable or metastatic disease whose tumors expressed PD-L1 — also showed the combination of pembrolizumab (Keytruda, Merck) and chemotherapy was well-tolerated.
“There is a significant need for treatment regimens that can help women with metastatic triple-negative breast cancer,” Javier Cortes, MD, PhD, head of the breast cancer program at IOB Institute of Oncology, Quironsalud Group in Spain, said in a Merck-issued press release. “The results of this study demonstrate that, if approved, Keytruda in combination with chemotherapy may offer certain women a new option for first-line treatment.”
Results of three prior trials showed monotherapy with the anti-PD-1 agent pembrolizumab induced antitumor activity with a manageable safety profile for patients with metastatic triple-negative breast cancer.
The double-blind KEYNOTE-355 trial assessed chemotherapy with or without pembrolizumab for 847 patients with previously untreated, locally recurrent inoperable or metastatic disease.
All patients had a disease-free interval of at least 6 months.
Cortes and colleagues randomly assigned 566 patients pembrolizumab plus one of three chemotherapy regimens — nab-paclitaxel, paclitaxel or gemcitabine/carboplatin. The other 281 patients received placebo plus chemotherapy.
Treatment continued for up to 35 cycles of pembrolizumab or placebo, or until disease progression or unacceptable toxicity.
Researchers stratified by chemotherapy type (taxane vs. gemcitabine/carboplatin), PD-L1 status (combined positive score [CPS] < 1 or 1) and whether patients had undergone prior neoadjuvant treatment with the same class of chemotherapy.
PFS assessed by blinded independent central review and OS, by tumor PD-L1 expression and among all patients, served as dual primary endpoints.
Median follow-up was 17.5 months in the pembrolizumab group and 15.5 months in the placebo group.
Results showed the addition of pembrolizumab to chemotherapy significantly improved PFS among patients with a CPS of 10 or higher (median, 9.7 months vs. 5.6 months; HR = 0.65; 95% CI, 0.49-0.86).
The PFS difference between pembrolizumab and placebo among patients with a CPS of 1 or higher did not meet the boundary for statistical significance (median, 7.6 months vs. 5.6 months; HR = 0.74; 95% CI, 0.61-0.9), and formal testing in the intention-to-treat population was not performed (median, 7.5 months vs. 5.6 months; HR = 0.82; 95% CI, 0.69-0.97). However, the treatment effect of pembrolizumab increased with PD-L1 enrichment, researchers noted.
Follow-up is continuing for OS.
Researchers reported no new safety concerns. A comparable percentage of patients in the pembrolizumab and placebo groups experienced any-grade treatment-related adverse events (96.3% vs. 95%) or grade 3 to grade 5 treatment-related adverse events (68.1% vs. 66.9%). Two deaths due to treatment-related adverse events occurred in the pembrolizumab group, whereas none occurred in the placebo group.
The most common grade 3 to grade 5 treatment-related adverse events in the pembrolizumab group were neutropenia (29.7%), decreased neutrophil count (17.4%) and anemia (16.4%), whereas the most common of these in the chemotherapy-alone group were neutropenia (29.9%), decreased neutrophil count (20.3%) and anemia (14.6%).
A higher percentage of patients assigned pembrolizumab discontinued treatment due to adverse events (18.1% vs. 11%).
One-quarter (25.6%) of patients assigned pembrolizumab experienced immune-mediated adverse events, compared with 6% of those assigned chemotherapy alone. The most common immune-mediated adverse event in the pembrolizumab group was hypothyroidism (15.5%).
Grade 3 or grade 4 immune-mediated adverse events and infusion reactions occurred among 5.5% of patients assigned pembrolizumab and 0% assigned placebo. – by Mark Leiser
Reference:
Cortes J, et al. Abstract 1000. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
Disclosures: Merck funded this study. Cortes reports research funding to his institution from, consultant/advisory roles with, honoraria from, stock or other ownership interests in, or travel, accommodations or expenses from AstraZeneca, Bayer, Celgene, Cellestia Biotech, Clovis Oncology, Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Guardant Health, MedSIR, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Seattle Genetics, Servier and other pharmaceutical companies. Please see the abstract for all other researchers’ relevant financial disclosures.
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It is very exciting to see that a checkpoint inhibitor has activity with chemotherapy agents other than nab-paclitaxel (Abraxane, Celgene) for front-line therapy of triple-negative breast cancer. We currently only have randomized data for atezolizumab (Tecentriq, Genentech) in combination with nab-paclitaxel. This regimen is limited in that, unfortunately, many of our patients with triple-negative disease have a relatively short disease-free interval after completing neoadjuvant or adjuvant therapy that contains a taxane. In these cases, it is an important option to treat with alternative chemotherapy agents.
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Cortes J, et al. Abstract 1000. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.