Pre-Surgical Keytruda Provides Promising Advancement in TNBC Treatment

Adding the immunotherapy agent Keytruda (pembrolizumab) to pre-surgical chemotherapy led to significantly improved outcomes in patients with early triple-negative breast cancer (TNBC), according to a primary analysis of the phase 3 KEYNOTE-522 clinical trial.

Two groups of patients with stage 2 or stage 3 early TNBC were examined in this analysis: one group received pre-surgical (neoadjuvant) Keytruda plus chemotherapy and then chemotherapy after surgery, while the other had neoadjuvant chemotherapy plus a placebo and then chemotherapy after surgery.

KEYNOTE-522 Findings

The main goals of the study were pathologic complete response, which is defined as the complete disappearance of all cancer at the time of surgery, and event-free survival. Both study endpoints were met.

“We have previously shown that pathologic (complete response) was positive with the addition of (Keytruda) to chemotherapy. It increased and improved pathologic (complete response) from 51.2% in the control arm to 64.8% in the chemotherapy plus Keytruda arm,” Dr. Peter Schmid, professor of Cancer Medicine at the Barts Cancer Institute in London, said in an interview with CURE®.

Schmid continued, “We also have now presented long-term follow-up data in terms of event-free survival — the second primary endpoint — where with 39 months median overall survival, we show a statistically significant and again meaningful improvement in event-free survival.”

The three-year event-free survival rates are about 60% in the Keytruda group, compared with 24% in the placebo group.

Breaking Down the Findings by Cancer Subtype

Keytruda works by inhibiting PD-1, a protein found on immune cells that can mask cancer cells. When the drug stops PD-1/PD-L1 pathway from working, it helps the patient’s immune system recognize and attack the cancer. Interestingly, though, Schmid explained that there was not much difference in outcomes between patients whose tumors were PD-L1 positive and PD-L1 negative.

When it came to the stage of the cancer, there was a slightly better improvement in pathologic complete response rates for patients with lymph node involvement compared to those without disease in their lymph nodes.

“But in terms of event-free long-term survival and reduction of recurrences, we see a similar benefit whether the patients have stage 2 or stage 3 disease,” Schmid said.

Safety and Side Effects of Neoadjuvant Keytruda

Immunotherapy agents like Keytruda work by activating the patient’s immune system to find and fight cancer. In doing so, the introduction of one of these drugs can put patients at risk of developing immune-related side effects, which can affect any organ system in the body.

In KEYNOTE-522, Schmid said that the immune-related side effects were generally manageable, and that there were no new safety signals, meaning new side effects from Keytruda that were not previously observed in prior studies and patients being treated with the drug.

“So overall, if learned from the KEYNOTE-522 study is that the addition of one year of immune therapy to primary therapy for stage 2/stage 3 TNBC with six months of neoadjuvant chemotherapy and six months in the adjuvant setting, significant improved both pathologic complete response rates and — more importantly — long-term outcomes, reducing recurrences in these patients significantly,” Schmid concluded.

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