Dr Naert meets Dr Punie: the KEYNOTE 522 trial

In this discussion, Dr Eline Naert, a medical oncologist at Ghent University Hospital, and Dr Kevin Punie, from GZA Antwerp, delve into the five-year event-free survival analysis of the KEYNOTE 522 trial, which involved adding pembrolizumab to neoadjuvant chemotherapy in stage 2 and 3 early triple-negative breast cancer patients.

Dr Punie highlights the significance of the updated five-year event-free survival analysis, emphasising that this period captures the majority of benefit regarding early relapses. The analysis reveals a stable hazard ratio of 0.63, but notably, an absolute improvement of 9% in event-free survival in the combination arm compared to the chemotherapy-only arm. This level of clinical benefit is comparable to the addition of trastuzumab in early HER2-positive disease.

The conversation shifts to sub-analysis, particularly the difference of 4% in pathologic complete response rates. Dr. Naert queries whether this difference justifies the additional toxicity of pembrolizumab. Dr. Punie points out that it’s a non-randomized analysis, making interpretation challenging. He underscores the main impact of pembrolizumab, which is increasing the number of patients with better outcomes. Even if one could predict PCR with chemotherapy alone, the 4% difference is not definitive, as the significance of achieving PCR may differ between chemo-only and chemo-plus-IO groups.

Regarding older patients (65 and above), Dr. Punie notes that in fit individuals, the regimen is considered. De-escalation of chemotherapy may be an option for patients with clear indications for pembrolizumab, such as stage 3 or node-positive disease, even in older individuals.

The conversation concludes with a question about managing patients found to be BRCA positive during the KEYNOTE 522 regimen. Dr. Punie suggests a sequential approach, given the need for adjuvant radiotherapy and the timeline for starting olaparib. He emphasises the importance of offering PARP inhibitors to these patients, considering the substantial risk of relapse they face.