Olubukola Ayodele, Breast Cancer Lead at University Hospitals of Leicester NHS Trust, Co-Convenor (Co-Chair) at London Global Cancer Week, shared on LinkedIn:
“ESMO2026 Day 2 | KEYNOTE-B49
Does immunotherapy have a role in HR+/HER2− metastatic breast cancer?
We’ve seen immunotherapy transform outcomes in triple-negative breast cancer. But can we achieve similar benefits in HR+/HER2− disease?
KEYNOTE-B49 provides an important, if disappointing, answer.
The trial:
Phase III, double-blind study randomising 342 patients with PD-L1 CPS ≥1, HR+/HER2− advanced breast cancer to:
• Pembrolizumab + chemotherapy
• Placebo + chemotherapy
Patients had progressed after endocrine therapy and were candidates for first-line chemotherapy. Almost 99% had received CDK4/6 inhibitors.
The primary endpoint was PFS, with OS a key secondary endpoint.
The results:
Progression-free survival:
- 6.7 vs 6.0 months
- HR 0.74 (95% CI 0.58–0.95)
- P=0.0089 (one-sided)
Overall survival:
- 21.0 vs 22.2 months
- HR 1.04 (95% CI 0.81–1.33)
- No survival benefit.
In patients with PD-L1 CPS ≥10:
- PFS: 7.5 vs 4.4 months (HR 0.59)
- OS: 22.9 vs 22.5 months (HR 0.82)
The CPS ≥10 findings are exploratory and do not establish a survival advantage.
Safety:
Grade ≥3 treatment-related adverse events occurred in 37.6% vs 32.7%.
Treatment-related discontinuations were higher with pembrolizumab: 11.2% vs 5.4%.
My take:
Although KEYNOTE-B49 met its primary endpoint, the absolute median PFS difference was only 0.7 months, without an OS benefit.
The higher PD-L1 subgroup showed a larger PFS effect, but the absence of a convincing OS signal makes it difficult to identify a population with meaningful clinical benefit.
Importantly, the trial underwent protocol amendments and sample-size reduction because of lower-than-expected PD-L1 prevalence, limiting its ability to answer some subgroup questions.
We also need to consider the rapidly changing treatment landscape.
With ADCs demonstrating substantial activity after endocrine therapy, adding immunotherapy to conventional chemotherapy becomes a harder proposition without clear survival or quality-of-life gains.
Statistical significance does not always translate into clinical significance.
KEYNOTE-B49 does not establish pembrolizumab plus chemotherapy as a new standard in HR+/HER2− metastatic breast cancer.
The biological question remains interesting, particularly whether immunotherapy could be more effective in combination with ADCs or in better-defined molecular subgroups.”
You can also read: 20 Posts Not to Miss from ESMO Congress 2026: Day 2
