53808 Adjuvant Pembrolizumab Versus Placebo in Stage IIB or IIC Melanoma: Exploratory Post Hoc Analyses of Patients with New Primary Melanoma and Other Skin Cancers from the Phase 3 KEYNOTE-716 Study

Background: The phase 3 KEYNOTE-716 study (NCT03553836) showed improved RFS (HR, 0.62 [95% CI, 0.49-0.79]) and DMFS (HR, 0.59 [95% CI, 0.44-0.79]) with adjuvant pembrolizumab versus placebo in stage IIB or IIC melanoma. We describe additional post hoc analyses from KEYNOTE-716.

Methods: Patients ≥12 years with newly diagnosed, resected stage IIB or IIC melanoma were randomly assigned 1:1 to receive pembrolizumab 200 mg (adult) or 2 mg/kg (pediatric) intravenously Q3W or placebo for ≤17 cycles. A post hoc sensitivity RFS analysis, in which new primary melanoma were counted as events, was conducted in all randomized patients.

Results: Of 976 patients, 487 were assigned to pembrolizumab and 489 to placebo. Median follow-up was 39.4 months (range, 26.0-51.4). Overall, 35 patients (7.2%) in the pembrolizumab group and 58 (11.9%) in the placebo group were diagnosed with new skin cancer. Diagnosis of new primary melanoma (2.3% vs 1.8%) and new primary melanoma in situ (1.2% vs 1.8%) was similar between pembrolizumab and placebo groups. Compared with pembrolizumab, basal cell carcinoma (3.9% vs 5.3%) and squamous cell carcinoma (1.6% vs 3.9%) were more common in the placebo group. In the sensitivity analysis, RFS was improved with pembrolizumab (HR, 0.65 [95% CI, 0.52-0.81]). The 36-month RFS rate was 73.4% for the pembrolizumab group and 61.2% for the placebo group.

Conclusion: The results suggest that patients with stage IIB or IIC melanoma have a high risk of developing new skin cancer. The RFS benefit of adjuvant pembrolizumab over placebo remained after accounting for new primary melanoma.