Neoadjuvant followed by adjuvant pembrolizumab in melanoma: time biases in the data analysis of the SWOG S1801 trial.

The SWOG S1801 trial investigated the role of pembrolizumab, an anti-PD1 immune checkpoint inhibitor, in the perioperative setting of stage III or IV melanoma. This phase 2 trial compared two groups: one receiving pembrolizumab both before and after surgery (neoadjuvant-adjuvant), and another receiving it only post-surgery (adjuvant-only), with event-free survival (EFS) as the primary endpoint. Neoadjuvant strategies, involving pre-surgical drug administration, potentially offer rapid tumor control and a unique opportunity to assess tumor response. However, they may expose to toxicity and delay or preclude surgery. The study met its primary endpoint, with a 72 % EFS rate in the neoadjuvant-adjuvant group, and 49 % in the adjuvant group. Here, we question the results' applicability with three potential limitations. Key concerns include an arbitrary rule in event assignment, possibly affecting the event distribution over time. Second, different rates of early censoring between groups introduce the possibility of informative censoring, which could have led to an artefactual benefit in EFS. Lastly, phase 2 trial results, by definition, carry risk of fluke results, and should be confirmed in phase 3 trial before wide adoption. Collectively, these factors must be integrated into a careful interpretation of the SWOG S1801 trial outcomes. More robust data are needed to fully appraise strengths and limitations of neoadjuvant pembrolizumab in melanoma treatment.