Pembrolizumab Improves Event-Free Survival in Early TNBC


Lee Schwartzberg, MD, discusses the results of the KEYNOTE-522 trial of pembrolizumab in patients with early triple-negative breast cancer.

Lee Schwartzberg, MD, chief medical director of West Cancer Center and chief of the division of hematology/oncology at the University of Tennessee Health Science Center, discusses the results of the KEYNOTE-522 (NCT03036488) trial of pembrolizumab (Keytruda) in patients with early triple-negative breast cancer (TNBC).

In the phase 3 trial, 1174 patients with previously untreated stage II or stage III TNBC were randomized 2:1 to receive neoadjuvant chemotherapy using carboplatin, paclitaxel, doxorubicin, and cyclophosphamide in addition to either 200 mg of pembrolizumab or placebo every 3 weeks, according to Schwartzberg. After surgery, patients received adjuvant pembrolizumab or placebo every 3 weeks for up to 9 cycles.

The primary end points were pathological complete response (pCR) at the time of definitive surgery and event-free survival (EFS) in the intent-to-treat population. According to Schwartzberg, the study met its success criterion for pCR at the first interim follow-up, with a pCR of 64.8% with pembrolizumab versus 51.2% with chemotherapy alone. At a median follow-up of 39 months, EFS was 84.5% with pembrolizumab compared with 76.8% with chemotherapy alone (HR, 0.63; 95% CI, 0.48-0.82; P = .00031).

Schwartzberg says that due to the favorable efficacy results, pembrolizumab is becoming the standard of care for both node-positive and node-negative patients with stage II or III TNBC.


0:08 | The study that has led to approval in this case with pembrolizumab, again, is KEYNOTE-522. That was a large trial and patients received aggressive chemotherapy with 4 drugs, and that included carboplatin, paclitaxel, [doxorubicin] or another anthracycline, and cyclophosphamide, all given prior to surgery. And they also either received pembrolizumab every 3 weeks with that, or placebo.

The results when initially published showed an improvement in the pCR rate which was substantial. So that's the first surrogate marker that pembrolizumab was getting something there. And now we have 3-year EFS of the data, which is, if you will, a harder end point. And it shows almost an 8% improvement in the risk of developing recurrent disease if you get pembrolizumab, which is really very substantial. So that has become the standard of care.

Now in KEYNOTE-522, the pembrolizumab was given both in the neoadjuvant setting and in the adjuvant setting, meaning after the surgery, whether you had a pCR rate or not, patients continued pembrolizumab and so it's based on that entire year of therapy; although not all patients did that, the majority did. So that has become the standard of care now to use a KEYNOTE–522-type of program to treat patients with stage II or III TNBC, and that includes both node-negative and node-positive patients.

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