1098P - Anti-PD1-based neoadjuvant therapy in resectable stage III or IV melanoma patients: A systematic review and meta-analysis

Background

Neoadjuvant therapy (NAT) with immunotherapy (anti-PD1-based) has shown promising event-free survival (EFS) and pathologic complete response (pCR) in resectable melanoma patients. We performed a systematic review and meta-analysis to evaluate anti-PD1-based NAT for stage III and IV resectable melanoma.

Methods

We searched PubMed, Scopus, and Cochrane Library databases for clinical trials and observational cohort studies. Outcomes of interest were pCR, major pathologic response (MPR), EFS, and overall survival (OS). Subgroups analysis included clinical stages and mucosal and acral melanomas (MM/AM) subpopulation. Heterogeneity was examined with I2 statistics; We used a DerSimonian and Laird random effects model.

Results

Eleven studies were included, comprising nine phase II/Ib clinical trials and two observational cohort studies with 486 patients. Of them, 85% had cutaneous melanoma, and 15% had MM/AM. Overall, 43% received single-agent NAT. In a pooled analysis, the pCR rate was 35.1% (95%CI 25.7-44.4). Stage III patients achieved a pCR of 36.9% (95%CI 28.9-71.5), whereas studies including stages III/IV reported pCR in 34.1% (95%CI 19.9-48.4). Single-agent therapy led to pCR in 30.5% (95%CI 20.2-40.9) of patients, while those treated with combination therapy had a pCR rate of 42.1% (95%CI 25.6-58.5). MPR was reached in 49.0% (95% 39.6-58.5) of patients. 231 (82.4%) remained free-of-events with a minimum follow-up of 14.6 months. OS was 90.1% (95%CI 86.0-93.1) in two years (27 deaths). Overall pathological response (CR+MPR+PR) was seen in 71.2% (95%CI 63.5-79.0) of patients, and the overall radiographic response in 50.8% (95%Cl 45.0-56.5). According to pCR, responders had a greater EFS than non-responders with an OR of 0.10 (95%CI 0.02-0.49 p=0.004). Among MM/AM, 19.9% (95%CI 7.8-34.9) of patients had pCR. There were no treatment-related deaths or delays of surgery.

Conclusions

Our study supports anti-PD1-based NAT anti-tumor activity in patients with resectable melanoma. Patients with pCR and stage III seem to benefit most from NAT, while rare melanomas still have a worse response. Other ongoing studies and more mature data are needed to confirm our findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M.F. Ribeiro: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. All other authors have declared no conflicts of interest.