Pembrolizumab

An open-label phase II study (SWOG S1801 [NCT03698019]) conducted at 90 sites in the United States enrolled 313 patients with resectable macroscopic stage IIIB to stage IV melanoma. Patients were randomly assigned (1:1) to receive either three cycles of neoadjuvant pembrolizumab (200 mg intravenously [IV] every 3 weeks) followed by surgery and fifteen cycles of adjuvant pembrolizumab (n = 154 patients) or primary surgery followed by eighteen cycles of adjuvant pembrolizumab (n = 159 patients).[20] The primary end point was EFS in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Exclusion criteria included prior immunotherapy for melanoma, active autoimmune disease in patients who had received systemic treatment within 2 years before trial entry, uveal melanoma, and any history of brain metastasis.

An open-label phase II study (SWOG S1801 [NCT03698019]) conducted at 90 sites in the United States enrolled 313 patients with resectable macroscopic stage IIIB to stage IV melanoma. Patients were randomly assigned (1:1) to receive either three cycles of neoadjuvant pembrolizumab (200 mg intravenously [IV] every 3 weeks) followed by surgery and fifteen cycles of adjuvant pembrolizumab (n = 154 patients) or primary surgery followed by eighteen cycles of adjuvant pembrolizumab (n = 159 patients).[20] The primary end point was EFS in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Exclusion criteria included prior immunotherapy for melanoma, active autoimmune disease in patients who had received systemic treatment within 2 years before trial entry, uveal melanoma, and any history of brain metastasis.

The median duration of follow-up was 14.7 months in both groups. A total of 105 events occurred (38 in the neoadjuvant-adjuvant group and 67 in the adjuvant-only group). EFS was significantly longer in the neoadjuvant-adjuvant group than in the adjuvant-only group (P = .004). The EFS rate at 2 years was 72% (95% confidence interval [CI], 64%–80%) in the neoadjuvant-adjuvant group and 49% (95% CI, 41%–59%) in the adjuvant-only group.[20][Level of evidence B1]

An open-label phase II study (SWOG S1801 [NCT03698019]) conducted at 90 sites in the United States enrolled 313 patients with resectable macroscopic stage IIIB to stage IV melanoma. Patients were randomly assigned (1:1) to receive either three cycles of neoadjuvant pembrolizumab (200 mg intravenously [IV] every 3 weeks) followed by surgery and fifteen cycles of adjuvant pembrolizumab (n = 154 patients) or primary surgery followed by eighteen cycles of adjuvant pembrolizumab (n = 159 patients).[20] The primary end point was EFS in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Exclusion criteria included prior immunotherapy for melanoma, active autoimmune disease in patients who had received systemic treatment within 2 years before trial entry, uveal melanoma, and any history of brain metastasis.

At the time of data cutoff, 36 deaths (14 in the neoadjuvant-adjuvant group and 22 in the adjuvant-only group) were reported. This small number of deaths precluded a comparison of overall survival (OS). The benefit of neoadjuvant-adjuvant pembrolizumab was seen across all subgroups of patients including those with BRAF pathogenic variants.

An open-label phase II study (SWOG S1801 [NCT03698019]) conducted at 90 sites in the United States enrolled 313 patients with resectable macroscopic stage IIIB to stage IV melanoma. Patients were randomly assigned (1:1) to receive either three cycles of neoadjuvant pembrolizumab (200 mg intravenously [IV] every 3 weeks) followed by surgery and fifteen cycles of adjuvant pembrolizumab (n = 154 patients) or primary surgery followed by eighteen cycles of adjuvant pembrolizumab (n = 159 patients).[20] The primary end point was EFS in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Exclusion criteria included prior immunotherapy for melanoma, active autoimmune disease in patients who had received systemic treatment within 2 years before trial entry, uveal melanoma, and any history of brain metastasis.

Among the 152 patients in the neoadjuvant–adjuvant group who had received at least one dose of pembrolizumab, 11 (7%) had at least one grade 3 or 4 adverse event that was deemed by the investigators to be related to pembrolizumab. The incidence of adverse events of grade 3 or higher during adjuvant therapy was similar in the two groups (12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group). No new toxic effects of pembrolizumab were observed in either trial group. No deaths attributed by the investigators to pembrolizumab occurred in either group.