Patients with early-stage triple-negative breast cancer demonstrated improved survival outcomes after treatment with perioperative (time around surgery) Keytruda (pembrolizumab) with chemotherapy, followed by Keytruda after surgery, according to a presentation at the 2024 ESMO Congress.
Findings from the phase 3 KEYNOTE-522 study were presented, which showed that the perioperative Keytruda-chemotherapy combination reduced the risk of death by 34%, compared with patients who received placebo (inactive drug) plus chemotherapy.
“Most importantly, [data from the study] demonstrated that [the Keytruda regimen] reduced the risk of death by 34%,” lead study author Dr. Peter Schmid, of Barts Cancer Institute at Queen Mary University in London, said in a press briefing at the ESMO Congress.
The Effect of Keytruda-Chemotherapy Versus Placebo-Chemotherapy Combinations
In the study, patients were randomly assigned to receive either Keytruda plus chemotherapy or placebo plus chemotherapy as first-line treatment perioperatively. After, patients in the respective treatment groups received Keytruda or placebo plus more chemotherapy after undergoing surgery.
The trial’s dual primary end points (main results measured at the end of the study) were pathological complete response (pCR; no more signs of cancer after treatment) rate and event-free survival (EFS; time after treatment when patients remain free from complications or events caused by cancer) in the intention-to-treat population.
Secondary end points included pCR and EFS in patients with PD-L1-positive tumors, and overall survival (OS; time patients live, regardless of disease status) among all patients and those with PD-L1-positive tumors.
At a median follow-up of 75.1 months, 784 patients treated in the Keytruda-chemotherapy group achieved a five-year OS rate of 86.6% versus 81.7% for 360 patients in the placebo group. The OS event rates were 14.7% and 21.8% for the Keytruda-chemotherapy and placebo groups, respectively.
Previously reported data, published in The New England Journal of Medicine, from the first interim analysis of KEYNOTE-522 showed that patients in the Keytruda group achieved a pCR rate of 64.8% compared with 51.2% in patients from the placebo group, at a median follow-up of 15.5 months.
Additionally, prior data from the fourth interim analysis, also published in The New England Journal of Medicine, demonstrated that the Keytruda regimen led to a significant improvement in EFS versus the placebo regimen. The 36-month EFS rate was 84.5% in the Keytruda group versus 76.8% in the placebo group.
In July 2021, the FDA approved Keytruda plus chemotherapy as a neoadjuvant (presurgical) treatment, then continued as Keytruda only as a treatment after surgery, for the treatment of patients with high-risk, early-stage triple-negative breast cancer based on prior data from KEYNOTE-522.
More from the KEYNOTE-522 Study
Updated efficacy analysis showed that the Keytruda regimen maintained a significant improvement in EFS versus the placebo regimen in the overall population. The five-year EFS rates were 81.2% for the Keytruda group versus 72.2% for the placebo group. EFS events were reported in 20.3% of patients in the experimental group versus 29.2% of patients in the control group.
Patients who achieved a pCR in the study also experienced an OS benefit, regardless of the treatment group. For responders, the five-year OS rate was 95.1% in 495 patients from the Keytruda group versus 94.4% in 217 patients from the placebo group. In non-responders, the five-year OS rate was 71.8% in 289 patients from the Keytruda group versus 65.7% in 173 patients from the placebo group.
Eligible patients enrolled in the trial must have been at least 18 years old, with triple-negative breast cancer in all foci (can only view tumor cells microscopically). Patients needed to have newly diagnosed, previously untreated, nonmetastatic disease, defined as tumor stage T1c, nodal stage N1-2, or tumor stage T2-4, nodal stage N0-2. Eligible patients had an ECOG performance status of 0 or 1 (meaning patients can perform daily tasks independently or with some restrictions) and adequate organ function. Notably, those with bilateral or multifocal primary tumors and inflammatory breast cancers were allowed to participate, according to the presentation.
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