Pembrolizumab Shows EFS Benefit in TNBC Without Complete Response

Lajos Pusztai, MD, DPhil, discusses key takeaways from analysis of the KEYNOTE-522 clinical trial of pembrolizumab plus chemotherapy in the neoadjuvant or adjuvant setting for patients with triple-negative breast cancer.

Lajos Pusztai, MD, DPhil, professor of medicine and coleader of Genetics, Genomics, and Epigenetics at Yale Cancer Center, discusses key takeaways from analysis of the KEYNOTE-522 (NCT03036488) clinical trial of pembrolizumab (Keytruda) plus chemotherapy in the neoadjuvant or adjuvant setting for patients with triple-negative breast cancer (TNBC).

The phase 3 KEYNOTE-522 study randomly assigned patients with stage II or III TNBC 2:1 to receive neoadjuvant pembrolizumab or placebo plus chemotherapy, followed by definitive surgery, then adjuvant pembrolizumab or placebo.

Pusztai says that the pembrolizumab benefited patients who had a pathologic complete response (pCR) but also appeared to benefit many who had a worse response to treatment based on their event-free survival (EFS).

Those with residual cancer burden scores of 2 (RCB2) which were the largest subpopulation that did not have a complete response, had a 3-year EFS rate of 75% with pembrolizumab versus 56% with chemotherapy alone, translating to an improvement in reduction of risk of local or distant recurrence, progression, or death. According to Pusztai, the greatest difference in the arms was a reduced risk of distant metastatic recurrence with pembrolizumab.

TRANSCRIPTION:

0:08 | The most important finding from my presentation is that the benefit from pembrolizumab extended beyond just increasing the pCR rates. Many patients who did not achieve pCR also benefited from pembrolizumab. We see this by plotting their EFS by the various residual disease categories for those who had less than a complete response. The largest statistically clearly significant benefit was seen among those who are in the RCB2 category, which happens to be the largest subpopulation among those who do not achieve a complete response.

0:56 | That was approximately 20% of the entire study population on the pembrolizumab arm and the chemotherapy alone arm combined that had this RCB2 extent of residual disease. If they were randomized to the pembrolizumab arm, the EFS at 3 years was 75% compared to only 56% in those who only received chemotherapy with the placebo. That's almost a 20% improvement in EFS. This means that we avoided in 20% of the patients, either local recurrence, distant recurrence, or progression [or death] during the neoadjuvant phase. In fact, the events that pembrolizumab prevented most were distant metastatic recurrences.