Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas

Compared with the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improved event-free survival in patients with resectable melanoma, the first results of the phase 2 SWOG S1808 trial demonstrated.

A current fundamental question for treating patients with resectable cancer is whether treatment with immunotherapy before surgery induces an enhanced anti-tumour immune response or simply delays curative surgery. In a small melanoma stage III patient cohort (n=20), neoadjuvant immunotherapy induced an immune response from a larger population of T cells compared with adjuvant immunotherapy [1].

To follow-up on this preliminary study, Dr Sapna Patel (MD Anderson Cancer Center, TX, USA) presented the first results of the phase 2 randomised SWOG S1808 trial (NCT03698019), which compared neoadjuvant pembrolizumab with adjuvant pembrolizumab in patients with resectable, stage III–IV melanoma [2].

The SWOG S1808 trial randomised 313 patients with resectable, stage III–IV melanoma to an adjuvant arm consisting of surgery followed by a maximum of 18 cycles of pembrolizumab (200 mg every 3 weeks), or a neoadjuvant arm consisting of treatment with 3 cycles of pembrolizumab followed by surgery and 15 cycles of pembrolizumab. The primary endpoint of the study was event-free survival (EFS). An event was defined as no surgery due to progression or toxicity, failure to start adjuvant treatment within 84 days of surgery, melanoma recurrence after surgery, or death of any cause.

With a median follow-up of 14.7 months, EFS was significantly longer in the neoadjuvant arm compared with the adjuvant arm (HR 0.58; P=0.004). The 2-year EFS rate was 72% versus 49% (neoadjuvant vs adjuvant arm). Overall survival data are not yet mature. In the neoadjuvant arm, 14 of 38 events took place before surgery (compared with 1 of 67 events in the adjuvant arm). Tumour-related events occurred in 20% (n=31) of participants in the neoadjuvant arm versus 40% (n=61) of participants in the adjuvant arm. In the neoadjuvant arm, 9 participants achieved a radiological complete response and 59 participants achieved a radiological partial response. A central pathological review is underway. No new safety issues were observed.

“Compared with the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improved EFS in patients with resectable melanoma,” summarised Dr Patel.

1. Blank CU, et al. Nat Med. 2018;24(11):1655–1661.
2. Patel S, et al. Neoadjuvant versus adjuvant pembrolizumab for resected stage III-IV melanoma (SWOG S1801). Abstract LBA6, ESMO Congress 2022, 09–13 September, Paris, France.

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Posted on 16 November, 2022