Event-Free Survival Improvement Noted in KEYNOTE-522 Study for Patients With Triple-Negative Breast Cancer


Pembrolizumab plus chemotherapy as adjuvant/neoadjuvant therapy demonstrated positive even-free survival outcomes in the KEYNOTE-522 study for patients with triple-negative breast cancer.

Positive event-free survival (EFS) outcomes found with adjuvant/neoadjuvant pembrolizumab (Keytruda) plus neoadjuvant chemotherapy in the phase 3 KEYNOTE-522 (NCT03036488) study for patients with high-risk early-stage triple-negative breast cancer, Merck announced in a press release.

Investigators examined neoadjuvant pembrolizumab plus chemotherapy followed by single-agent pembrolizumab in the adjuvant setting compared with the neoadjuvant chemotherapy and adjuvant placebo. The phase 3 trial represents the first time an anti–PD-1 therapy has yielded a statistically significant EFS result in this patient population.

At the median follow-up of 39 months, investigators found that pembrolizumab had produced a statistically significant EFS benefit (HR, 0.63; 95% CI, 0.48-0.82; P = .00031), compared with chemotherapy alone. Investigators defined EFS as time from randomization to the first occurrence of disease progression precluding definitive surgery, local or distant recurrence, second primary cancer, or death.

At the 3-year follow-up, 84.5% patients in the pembrolizumab group were alive and did not experience an event compared with 76.8% of patients in the placebo group.

“Given the high rates of recurrence within the first 5 years of diagnosis, patients with high-risk early-stage TNBC need new treatment options,” Peter Schmid, MD, Centre for Experimental Cancer Medicine Lead at Barts Cancer Institute in London, England, said in a press release.

This was a double-blind randomized trial enrolled 1174 patients and randomized patients 2:1 to pembrolizumab every 3 weeks plus weekly paclitaxel with carboplatin every week or every 3 weeks for 4 cycles, followed by pembrolizumab plus cyclophosphamide every 3 weeks, and either doxorubicin or epirubicin for 4 cycles as neoadjuvant therapy prior to surgery, followed by 9 cycles of pembrolizumab every 3 weeks for adjuvant therapy post-surgery. The placebo arm received the same treatment except patients received the matching placebo instead of pembrolizumab.

As previously reported, the trial met 1 of 2 primary end points of pathological complete response (pCR), with 64.8% (95% CI, 59.9%-69.5%) of patients in the pembrolizumab/chemotherapy combination group achieving this outcome versus 51.2% (95% CI, 44.1%-58.3%) with chemotherapy.

For patients who were in the PD-L1–positive group, defined at those with a combined positive score of 10 or higher, there was a 33% reduced risk of EFS events with pembrolizumab compared with the placebo group (HR, 0.67; 95% CI, 0.49-0.92). In the PD-L1–negative group, patients receiving the pembrolizumab regimen had a reduced risk EFA events by 52% compared with the placebo-chemotherapy group (HR, 0.48; 95% CI, 0.28-0.85).

In 98.9% of patients receiving pembrolizumab, treatment-related adverse effects (TRAEs) occurred compared with 99.7% in the placebo group. Grade 3 or greater TRAEs occurred in 77.1% of patients on pembrolizumab compared with 73.3% receiving chemotherapy. In the pembrolizumab group, 0.5% of patients died and 0.3% died in the placebo-chemotherapy group.

Immune-mediated AEs (IMAEs) of any grade were found in 43.6% of patients receiving pembrolizumab and 21.9% receiving placebo-chemotherapy. The most commonly reported with pembrolizumab were infusion reactions and hypothyroidism. IMAEs led to death in 0.3% of the pembrolizumab group compared with none in the chemotherapy group.

Merck has submitted these new EFS data to the FDA for review. The FDA had previously issued a complete letter response to the company regarding a supplemental biologics license application for the agent in this indication, as they voted in favor of waiting for further data before approval.

“KEYNOTE-522 was designed to study whether the combined neoadjuvant and adjuvant regimen with Keytruda could help treat the cancer earlier. Now, with more than 3 years of follow-up, we see the potential of this approach. These event-free survival data are very encouraging for patients and show that this combination of Keytruda plus chemotherapy as neoadjuvant therapy, followed by single-agent Keytruda as adjuvant therapy, may offer women with high-risk early-stage TNBC a new treatment option for this aggressive disease,” Schmid said.


Keytruda (pembrolizumab) plus chemotherapy before surgery and continued as a single agent after surgery showed statistically significant event-free survival (EFS) results versus neoadjuvant chemotherapy alone in high-risk early-stage TNBC. News Release. July 15, 2021. Accessed July 16, 2021. https://bit.ly/3z1TbD5

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