medwireNews: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab significantly improves event-free survival (EFS) rates versus neoadjuvant chemotherapy alone in people with a new diagnosis of early-stage triple-negative breast cancer, KEYNOTE-522 study data show.
Speaking at the ESMO Virtual Plenary, Peter Schmid, from Queen Mary University London in the UK, said that the findings were “clinically meaningful” and “clearly support pembrolizumab plus platinum-containing neoadjuvant chemotherapy, followed by adjuvant pembrolizumab after surgery, as a new standard-of-care treatment regimen for patients with high-risk, early-stage triple-negative breast cancer.”
Prior analyses from the phase 3 trial showed that individuals who received pembrolizumab had a significantly higher pathologic complete response rate than those given placebo, at 64.8% versus 51.2%, as well as a trend for improved EFS.
In all, 1174 patients with previously untreated, nonmetastatic (stage T1c N1-2 or T2-4 N0-2), triple-negative disease were randomly allocated to treatment with neoadjuvant pembrolizumab 200 mg (n=784) or placebo (n=390) every 3 weeks, each given with four cycles of paclitaxel plus carboplatin, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide.
Following surgery, participants received adjuvant pembrolizumab or placebo for a further nine cycles or until recurrence or unacceptable toxicity.
In the current definitive EFS analysis, carried out after a median 39.1 months of follow-up, significantly fewer patients in the pembrolizumab group than in the placebo group had disease progression that precluded definitive surgery, a local or distant recurrence, a second primary cancer, or had died from any cause, at rates of 15.7% and 23.8%, respectively, and a hazard ratio (HR) of 0.63.
The 36-month EFS rate was 84.5% in the pembrolizumab group and 76.8% in the placebo group, with the median not reached in either group.
Schmid said that the effect of pembrolizumab “seems to be consistent across most subgroups.” In particular, people with PD-L1-positive disease have a similar level of benefit to those with PD-L1-negative disease, as do people with node-positive versus node-negative disease.
The most common EFS event was distant recurrence, which occurred in 7.7% of patients in the pembrolizumab group and 13.1% of those in the placebo group.
The researchers also observed a trend for improved overall survival (OS) among the individuals given pembrolizumab rather than placebo, with 3-year OS rates of 89.7% versus 86.9% and a non-significant HR of 0.72, but Schmid noted that the data are still immature and follow-up continues.
He also reported that adverse events (AEs) were “consistent with the known profiles of each regimen, with no new safety concerns.”
Grade 3 or worse treatment-related AEs were experienced by 77.1% of the pembrolizumab group and 73.3% of the placebo group, with events dominated by chemotherapy-related effects such as nausea, alopecia, and anemia. Immune-mediated AEs occurred at any grade in 43.6% and 21.9% of patients, respectively, while treatment-related deaths were recorded in a respective 0.3% and 0.0%.
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ESMO Virtual Plenary; 15–16 July 2021