LBA48 Pathologic response and exploratory analyses of neoadjuvant-adjuvant versus adjuvant pembrolizumab (PEM) for resectable stage IIIb-IV melanoma from SWOG S1801

Primary efficacy results from SWOG S1801 showed an improved event-free survival (EFS) in patients who received neoadjuvant-adjuvant (NAT) PEM compared to adjuvant (AT) PEM. In pooled analyses and smaller neoadjuvant studies, pathologic response has been suggested as an important surrogate marker of clinical outcome. S1801 was a randomized phase II trial for clinically detectable, resectable AJCC 8th edition stage IIIB-IV melanoma. Participants were randomized 1:1 to AT PEM (surgery then 18 doses of PEM q3w) or NAT PEM (3 doses pre-operative PEM, surgery, 15 doses PEM q3w). Sites submitted surgical specimens for central review. For determination of pathologic response to NAT, these specimens were assessed for percentage of necrosis and viable tumor by a single pathologist blind to the clinical results. As of August 31, 2023, 281 participants had surgery (138 NAT, 143 AT). Of those randomized to NAT, 109 specimens were reviewed for pathologic response, 89 were lymph node specimens. Pathologic response and recurrence-free survival (RFS) outcomes for these lymph node specimens are shown in the table. 130 of 138 NAT participants who underwent surgery had RECIST response data; 15 (12%) achieved complete response (CR), 50 (38%) partial response (PR) for an overall response rate of 50%; 50 (38%) experienced stable disease (SD), and 15 (12%) progression of disease (PD).Table: LBA48Path response N (%)NAT N=89pathologic complete response (pCR)36 (40%)pathologic near complete response (pnCR)10 (11%)pathologic partial response (pPR)26 (29%)pathologic non-response (pNR)17 (19%)2-year RFS1 by path response % (95% CI)N=89pCR (n=36)97% (92-100)pnCR (n=10)80% (59-100)pPR (n=26)73% (58-92)pNR (n=17)48% (28-82)2-year RFS1 by RECIST 1.1 responseN=130CR (n=15)93% (82-100)PR (n=50)89% (81-99)SD (n=50)64% (52-80)PD (n=15)67% (47-95)1RFS measured from date of surgery Open table in a new tab 1RFS measured from date of surgery The use of NAT with single-agent PEM in resectable stage IIIB-IV melanoma results in a 51% major pathologic response rate (pCR + pnCR) with 40% pathologic complete responses. 2-year RFS rates are highest in those achieving pathologic or radiographic response.