Methods and Study Design of KEYNOTE-522 for TNBC


Lajos Pusztai, MD, DPhil, discusses the methods and design of the phase 3 KEYNOTE-522 trial.

Lajos Pusztai, MD, DPhil, professor of Medicine (Medical Oncology), and co-leader of Genetics, Genomics, and Epigenetics at Yale Cancer Center, discusses the methods and design of the phase 3 KEYNOTE-522 (NCT03036488) trial.

In KEYNOTE-522, investigators evaluated treatment with pembrolizumab (Keytruda) plus chemotherapy administered in the neoadjuvant or adjuvant setting to patients with triple-negative breast cancer (TNBC) compared with placebo plus chemotherapy.

Among those included in the double-blind trial were patients with previously untreated stage 2 or 3 TNBC. Patients were randomized in a 2:1 fashion to receive either neoadjuvant therapy with 4 cycles of pembrolizumab at a dose of 200 mg or placebo every 3 weeks in combination with paclitaxel and carboplatin, followed 4 cycles of pembrolizumab or placebo plus doxorubicin/cyclophosphamide or epirubicin/cyclophosphamide. Then, patients were given either adjuvant pembrolizumab or placebo after definitive surgery every 3 weeks for up to a total of 9 cycles.


0:08 | KEYNOTE-522 was a randomized, double-blind placebo-controlled trial for stage 2 and stage 3 triple-negative breast cancer. Patients had to have a 2 cm or greater invasive cancer, or they could have a smaller tumor, but the lymph node involvement had to be noted as positive.

0:29 | Several years ago, we developed a method to quantify the extent of residual cancer, so if you have no residual cancer at all or no viable cancer at the completion of new adjuvant chemotherapy, then we call this a pathologic complete response, or RCB, residual cancer burden 0. But there is a huge range of viable residual cancer in a subset of patients. We developed a method that combines the maximum size of the cancer, the cellularity of the cancer, the number of lymph nodes, which are involved, and the size of the lymph node involvement into a single core, the core score that we call RCB, and this score could be used to categorize patients into RCB0, 1, 2, or 3. Then as the score increases, the extent of the residual disease increases and the expected survival or prognosis of the patient gets worse and worse.

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