Pembro-chemo improves PFS in Asian patients with inoperable/metastatic TNBC

The addition of pembrolizumab to chemotherapy led to better progression-free survival (PFS) compared with chemotherapy only in Asian patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC), according to a subgroup analysis of the KEYNOTE-355 study presented at ESMO Asia 2020.

This subgroup analysis comprised the 160 patients enrolled in Asian* countries in the phase III KEYNOTE-355 study. Adults with locally recurrent inoperable or metastatic TNBC and ECOG performance status 0–1 with a disease-free interval of ≥6 months were randomized 2:1 to receive intravenous pembrolizumab (200 mg Q3W up to 35 administrations) plus chemotherapy** or chemotherapy plus placebo, with chemotherapy continued until disease progression or toxicity.  

Patients in the pembrolizumab-chemotherapy and chemotherapy-alone groups had a median age of 55 and 50 years, respectively, 33.6 and 38.3 percent, respectively, had PD-L1 combined positive score (CPS) ≥10, and about two-thirds (65.5 and 61.7 percent, respectively) received gemcitabine/carboplatin as chemotherapy in this study. Patients were followed up for a median 25.7 months.

Overall, in the intention-to-treat (ITT) Asian population, there was a 39 percent reduction in progression or death with pembrolizumab plus chemotherapy vs chemotherapy alone (64.6 percent vs 80.9 percent; hazard ratio [HR], 0.61, 95 percent confidence interval [CI], 0.41–0.90), with a median PFS of 8.8 vs 6.7 months. [ESMO Asia 2020, abstract 43O]

The benefits were more pronounced among patients with PD-L1 CPS ≥10 (median 17.3 vs 5.6 months), with 52.6 and 77.8 percent of patients, respectively, experiencing PFS events (HR, 0.45, 95 percent CI, 0.22–0.91)

The PFS benefit with pembrolizumab plus chemotherapy vs chemotherapy alone was also noted in patients with CPS ≥1 (median 7.7 vs 5.6 months), with PFS events occurring in 63.0 and 86.1 percent, respectively (HR, 0.56, 95 percent CI, 0.36–0.89).

The PFS benefits noted with pembrolizumab-chemotherapy vs chemotherapy alone were evident across multiple subgroups including age, type of on-study chemotherapy, receipt of prior adjuvant or neoadjuvant chemotherapy, and number of metastatic sites.

Grade 3–4 treatment-related adverse events (TRAEs) occurred at a similar rate between the pembrolizumab-chemotherapy and chemotherapy-alone groups (77.9 percent vs 78.7 percent), but more often led to discontinuation of any drug in the pembrolizumab group (22.1 percent vs 8.5 percent). There were no fatal TRAEs. Common TRAEs in both groups were decreased neutrophil and white blood cell count. Immune-mediated AEs of any grade occurred in more pembrolizumab-chemotherapy than chemotherapy-alone recipients (25.7 percent vs 4.3 percent), with only pembrolizumab recipients experiencing grade 3–4 immune-mediated AEs (4.4 percent).

Findings comparable to main population

The PFS benefits with pembrolizumab-chemotherapy in the Asian population were similar to those of the overall ITT study population (n=847; median 7.5 vs 5.6 months; HR, 0.82), specifically in the 323 patients with PD-L1 CPS ≥10 (median 9.7 vs 5.6 months; HR, 0.65; p=0.0012). [J Clin Oncol 2020;38:1000]

“The safety and tolerability profiles in patients from the Asian region were [also] comparable to that of the overall study population. Pembrolizumab plus chemotherapy was tolerable [and] no new safety signals were identified,” noted study author Dr Mastura Md Yusof from Pantai Hospital, Kuala Lumpur, Malaysia.

“These findings support the addition of pembrolizumab to chemotherapy for the first-line treatment of Asian patients with metastatic TNBC with PD-L1 CPS ≥10,” she concluded.

“[These findings also suggest] that all our current doubts of using immunotherapy in TNBC are also valid for the Asian population,” pointed out discussant Dr Evandro de Azambuja from the Institut Jules Bordet, Brussels, Belgium.

Questions that need answering include identifying the appropriate chemotherapy partner for the immunotherapy drug, use of biomarkers to identify the population that would reap the most benefits from immunotherapy, and the long-term toxicities, both immune-related and financial, he said.