Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma.

BACKGROUND: While neoadjuvant immunotherapy for melanoma has shown promising results, the data have been limited by a relatively short follow-up time, with most studies reporting 2-year outcomes. The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death receptor 1 (PD-1) inhibition. PATIENTS AND METHODS: This is a follow-up study of a previously published phase Ib clinical trial of 30 patients with resectable stage III/IV cutaneous melanoma who received one dose of 200 mg IV neoadjuvant pembrolizumab 3 weeks before surgical resection, followed by 1 year of adjuvant pembrolizumab. The primary outcomes were 5-year overall survival (OS), 5-year recurrence-free survival (RFS), and recurrence patterns. RESULTS: We report updated results at 5 years of follow-up with a median follow-up of 61.9 months. No deaths occurred in patients with a major pathological response (MPR, <10% viable tumor) or complete pathological response (pCR, no viable tumor) (n = 8), compared to a 5-year OS of 72.8% for the remainder of the cohort (P = 0.12). Two of eight patients with a pCR or MPR had a recurrence. Of the patients with >10% viable tumor remaining, 8 of 22 patients (36%) had a recurrence. Additionally, the median time to recurrence was 3.9 years for patients with ≤10% viable tumor and 0.6 years for patients with >10% viable tumor (P = 0.044). CONCLUSIONS: The 5-year results from this trial represent the longest follow-up of a single-agent neoadjuvant PD-1 trial to date. Response to neoadjuvant therapy continues to be an important prognosticator with regard to OS and RFS. Additionally, recurrences in patients with pCR occur later and are salvageable, with a 5-year OS of 100%. These results demonstrate the long-term efficacy of single-agent neoadjuvant/adjuvant PD-1 blockade in patients with a pCR and the importance of long-term follow-up for these patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02434354.

Impact of chemotherapy on survival in surgically resected retroperitoneal sarcoma.

BACKGROUND: The role of systemic chemotherapy (CT) in the multimodality treatment strategy for retroperitoneal sarcomas (RPS) remains controversial. We hypothesized that chemotherapy does not improve overall survival for patients with surgically resected RPS. METHODS: The National Cancer Database was used to identify all patients with RPS that underwent surgical resection from 1998 to 2011. Univariate and multivariable Cox proportional hazards modeling were used to assess overall survival (OS) and logistic regression was used for associations. Propensity score (PS) modeling was performed to create balanced cohorts for analysis. RESULTS: A total of 8653 patients with surgically resected RPS were identified; 1525 (17.6%) received CT; 10.6% of patients (n = 163) in the neoadjuvant setting. Factors associated with receipt of CT included moderate (OR 2.3) to poorly differentiated (OR 4.3) tumors, leiomyosarcoma (OR 1.8) or undifferentiated pleomorphic sarcoma (OR 2.3) histology, and R2 resection status (OR 2.2) (all p < 0.05). Unadjusted median OS for patients receiving CT compared to surgery alone was 40 vs 68.2 months respectively (p < 0.01). Following propensity score matching, worse median OS persisted among the CT cohort (40 vs 52 months, p = 0.002). Receipt of chemotherapy was not associated with improved long term survival in adjusted models for the raw and propensity matched cohorts (HR 1.17, 95% CI: 1.04-1.31; p = 0.009). CONCLUSION: Current available chemotherapy regimens for RPS do not confer a survival benefit. Routine use of chemotherapy for RPS should be discouraged until new effective systemic agents become available.