According to pathologic response and exploratory analyses from the phase 2 SWOG S1801 study, treatment with neoadjuvant and adjuvant pembrolizumab resulted in promising response rates among patients with resectable stage IIIB-IV melanoma. Additionally, pathologic and radiographic response was associated with higher recurrence-free survival (RFS) rate at 2 years.

These results were presented at the European Society for Medical Oncology Congress in Madrid, Spain, by lead author, Sapna Patel, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas. 

Previously reported efficacy results from this trial “showed an improved event-free survival in patients who received neoadjuvant-adjuvant [pembrolizumab] compared to adjuvant [pembrolizumab],” stated Dr Patel and coauthors. “In pooled analyses and smaller neoadjuvant studies, pathologic response has been suggested as an important surrogate marker of clinical outcome.”

In this study, 281 patients were randomized on a 1-to-1 basis to receive either 18 doses of adjuvant pembrolizumab once every 3 weeks following surgical resection (n = 143) or 3 doses of pre-operative pembrolizumab followed by surgical resection and 15 doses of post-operative pembrolizumab once every 3 weeks (n = 138). Surgical specimens were submitted for central review. Based on the percentage of necrosis and viable tumor, pathologic response in the neoadjuvant-adjuvant arm was assessed by a single pathologist blind to clinical results. 

At the data cutoff point, 109 specimens from patients in the neo/adjuvant arm were reviewed for pathologic response. Of 138 patients in this arm that underwernt surgery, 130 had RECIST response data. Complete response was achieved in 15 patients and partial response was achieved in 50 patients. Overall response rate was 50%. Stable disease was established in 50 patients. There were 15 patients who experienced disease progression. Patients in the neo/adjuvant arm who experienced a pathologic complete response (n = 36), had a 2-year recurrence-free survival rate of 97%. Patients with a pathologic non-response (n = 17), had a 2-year RFS rate of 48%. Patients with a complete response by RECIST v1.1 (n = 15), had a 2-year RFS rate of 93%, while patients with progressive disease (n = 15) had a RFS rate of 67%.

“The use of [neoadjuvant-adjuvant] with single-agent [pembrolizumab] in resectable stage IIIB-IV melanoma results in a 51% major pathologic response rate with 40% pathologic complete responses,” concluded Dr Patel and coauthors. “2-year RFS rates are highest in those achieving pathologic or radiographpic response."

Source:

Patel S, Othus M, Wright P, et al. Pathologic response and exploratory analyses of neoadjuvant-adjuvant versus adjuvant pembrolizumab (PEM) for resectable stage IIIb-IV melanoma from SWOG S1801. Presented at the 2023 ESMO Congress; October 20-24, 2023; Madrid, Spain. Abstract LBA48