Neoadjuvant pembrolizumab outperforms it as adjuvant in resectable melanoma

Compared with the same treatment given entirely in the adjuvant setting, this application improves event-free survival in resectable stage III–IV melanoma patients.

Neoadjuvant immunotherapy appears to induce an immune response from a larger population of T cells

A current fundamental question in the treatment of patients with resectable cancer is whether treatment with immunotherapy before surgery induces an enhanced anti-tumour immune response or simply delays curative surgery. The rationale in favour of neoadjuvant immunotherapy is that, compared with adjuvant immunotherapy, it has been shown to induce an immune response from a larger population of T cells1.

To further prove this hypothesis, 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 melanoma2.

SWOG S1808 randomised 313 patients with resectable, stage III–IV melanoma to an adjuvant arm consisting of surgery followed by a maximum of 18 cycles 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.

Neoadjuvant pembrolizumab favoured EFS in all pre-specified subgroups

With a median follow-up of 14.7 months, EFS was significant longer in the neoadjuvant arm compared with the adjuvant arm (HR 0.58; P=0.004). Neoadjuvant pembrolizumab favoured EFS in all pre-specified subgroups, e.g. age, stage, LDH, ulceration, and BRAF status. Two-year EFS rate was 72% versus 49%. Overall survival data are not yet mature. In the neoadjuvant arm, 14 of 38 events took place before surgery (vs 1 of 67 events in the adjuvant arm). Tumour-related events occurred in 20% (n=331) of participants in the neoadjuvant arm versus 40% (n=61) of participants in the adjuvant arm. In the neoadjuvant arm, 9 patients achieved a radiological complete response, and 59 patients achieved a radiological partial response. 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.

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