{"id":655639,"date":"2026-10-24T10:10:09","date_gmt":"2026-10-24T10:10:09","guid":{"rendered":"https:\/\/www.newsbeep.com\/il\/655639\/"},"modified":"2026-10-24T10:10:09","modified_gmt":"2026-10-24T10:10:09","slug":"keynote-b49-trial-immunotherapy-in-hr-her2%e2%88%92-breast-cancer","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/il\/655639\/","title":{"rendered":"KEYNOTE-B49 Trial: Immunotherapy in HR+\/HER2\u2212 Breast Cancer"},"content":{"rendered":"

The phase III KEYNOTE-B49<\/a> trial met its primary progression-free survival (PFS) endpoint with pembrolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with PD-L1\u2013positive, hormone receptor\u2013positive (HR+), HER2-negative advanced breast cancer after endocrine-based therapy.<\/p>\n

Median PFS was 6.7 versus 6.0 months, with a hazard ratio of 0.74. However, the final analysis did not demonstrate a statistically significant overall survival (OS) improvement. Treatment-related toxicity and discontinuations were more frequent with pembrolizumab.<\/p>\n

The findings were reported at ESMO 2026 in abstract LBA51.<\/p>\n

Background<\/p>\n

Patients with HR+\/HER2\u2212 advanced breast cancer whose disease progresses after endocrine-based therapy need additional treatment options. The role of immune checkpoint inhibition in this setting remains less well defined than in triple-negative breast cancer.<\/p>\n

KEYNOTE-B49 evaluated whether adding pembrolizumab to first-line chemotherapy could improve outcomes in patients with PD-L1\u2013positive disease following progression on endocrine-based treatment.<\/p>\n

\"KEYNOTE-B49<\/p>\n

Methods and Study Design<\/p>\n

KEYNOTE-B49 (NCT04895358<\/a>) was a randomized, double-blind, placebo-controlled phase III trial enrolling 342 patients with locally recurrent inoperable or metastatic HR+\/HER2\u2212 breast cancer, PD-L1 combined positive score (CPS) \u22651, and prior endocrine therapy who were candidates for first-line chemotherapy.<\/p>\n

Patients were randomized equally to:<\/p>\n

Pembrolizumab plus chemotherapy (n = 171): Pembrolizumab 200 mg every three weeks for up to 35 cycles, combined with physician\u2019s choice of paclitaxel, nab-paclitaxel, liposomal doxorubicin, or capecitabine.
\nPlacebo plus chemotherapy (n = 171): Placebo on the same schedule, combined with one of the chemotherapy options.<\/p>\n

The primary endpoint was PFS assessed by blinded independent central review according to RECIST v1.1 in the CPS \u22651 population. The key secondary endpoint was OS in the same population. Multiplicity was controlled at a one-sided \u03b1 of 0.025.<\/p>\n

A protocol amendment reduced the sample size because of low PD-L1 prevalence. Nearly all patients had previously received a CDK4\/6 inhibitor: 99.4% in the pembrolizumab arm and 98.8% in the placebo arm.<\/p>\n

Results<\/p>\n

The primary PFS analysis used a September 22, 2025 data cutoff, with median follow-up of 29.1 months. The final analysis used a March 16, 2026 cutoff, with median follow-up of 34.9 months.<\/p>\n

Primary PFS endpoint: Median PFS was 6.7 months (95% CI 6.2\u20138.3) with pembrolizumab plus chemotherapy versus 6.0 months (95% CI 4.2\u20138.1) with placebo plus chemotherapy. The HR was 0.74 (95% CI 0.58\u20130.95; one-sided P = 0.0089), meeting the prespecified statistical criterion and corresponding to a 26% reduction in the hazard of progression or death.
\nLandmark PFS: At the primary analysis, estimated 12-month PFS was 26.3% versus 20.3%, and estimated 24-month PFS was 15.0% versus 4.3%, respectively.
\nUpdated PFS: At the final cutoff, the descriptive PFS update remained consistent with the primary analysis (HR 0.74; 95% CI 0.58\u20130.95). Median PFS remained 6.7 versus 6.0 months. Updated 24-month PFS estimates were 14.1% versus 3.5%.
\nPFS in the CPS \u226510 subgroup: At the primary analysis, median PFS was 7.5 months with pembrolizumab plus chemotherapy versus 4.4 months with placebo plus chemotherapy (HR 0.59; 95% CI 0.35\u20130.98). This subgroup result should be interpreted separately from the multiplicity-controlled primary analysis.
\nOverall survival in the CPS \u22651 population: At the final analysis, median OS was 21.0 months (95% CI 18.9\u201322.9) versus 22.2 months (95% CI 17.6\u201326.3), respectively. There was no statistically significant improvement (HR 1.04; 95% CI 0.81\u20131.33; one-sided P = 0.6185).
\nOS in the CPS \u226510 subgroup: Among 36 patients per arm, median OS was 22.9 versus 22.5 months (HR 0.82; 95% CI 0.47\u20131.43). These results did not establish an OS benefit in this subgroup.
\nSafety: Grade \u22653 treatment-related adverse events occurred in 37.6% of patients receiving pembrolizumab plus chemotherapy versus 32.7% receiving placebo plus chemotherapy. Treatment-related adverse events led to treatment discontinuation in 11.2% versus 5.4%, respectively.<\/p>\n

\"KEYNOTE-B49\"<\/p>\n

Interpretation<\/p>\n

KEYNOTE-B49 demonstrated a statistically significant PFS improvement with pembrolizumab plus chemotherapy in the PD-L1 CPS \u22651 population. The difference in median PFS was modest, although the landmark estimates showed greater separation between treatment arms at later timepoints.<\/p>\n

The PFS improvement was not accompanied by a demonstrated OS benefit, and treatment-related toxicity and discontinuations were more frequent with pembrolizumab.<\/p>\n

The CPS \u226510 subgroup showed a numerically larger PFS treatment effect. However, this does not establish greater benefit relative to the CPS 1\u20139 subgroup without a treatment-by-biomarker interaction analysis.<\/p>\n

Conclusion<\/p>\n

KEYNOTE-B49 met its primary PFS endpoint in patients with PD-L1 CPS \u22651 HR+\/HER2\u2212 advanced breast cancer after endocrine-based therapy but did not demonstrate an OS benefit.<\/p>\n

The findings show improved disease control with pembrolizumab plus chemotherapy, accompanied by increased treatment-related toxicity and discontinuations. The CPS \u226510 subgroup findings require cautious interpretation and do not establish an OS benefit or a definitive threshold for selecting treatment.<\/p>\n","protected":false},"excerpt":{"rendered":"The phase III KEYNOTE-B49 trial met its primary progression-free survival (PFS) endpoint with pembrolizumab plus chemotherapy compared with…\n","protected":false},"author":2,"featured_media":655640,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[163,85,46],"class_list":["post-655639","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-il","tag-israel"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/655639","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=655639"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/655639\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/655640"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=655639"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=655639"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=655639"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}