PURPOSE: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space. METHODS: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. To continue on study, patients are required to have radiographic or clinical benefit. The coprimary end points are safety and pathologic complete response. Key secondary end points are response rate and organ-sparing at one year for patients who declined surgery. Exploratory analyses include interrogation of the tumor immune microenvironment using imaging mass cytometry. RESULTS: A total of 35 patients were enrolled, including 27 patients with colorectal cancer and eight patients with noncolorectal cancer. Among 33 evaluable patients, best overall response rate was 82%. Among 17 (49%) patients who underwent surgery, the pathologic complete response rate was 65%. Ten patients elected to receive one year of pembrolizumab followed by surveillance without surgical resection (median follow-up of 23 weeks [range, 0-54 weeks]). An additional eight did not undergo surgical resection and received less than 1 year of pembrolizumab. During the study course of the trial and subsequent follow-up, progression events were seen in six patients (four of whom underwent salvage surgery). There were no new safety signals. Spatial immune profiling with imaging mass cytometry noted a significantly closer proximity between granulocytic cells and cytotoxic T cells in patients with progressive events compared with those without progression. CONCLUSION: Neoadjuvant pembrolizumab in dMMR/MSI-H cancers is safe and resulted in high rates of pathologic, radiographic, and endoscopic response, which has implications for organ-sparing strategies.

OBJECTIVE: To estimate the effects of a laparoscopic scoring algorithm to triage patients with advanced ovarian cancer to immediate or delayed debulking to improve complete gross surgical resection rates and determine the resulting clinical outcomes. METHODS: We prospectively performed laparoscopic assessment on patients with suspected advanced-stage ovarian cancer from April 2013 to December 2016 to determine primary resectability at tumor reductive surgery. Patients with medically inoperable or distant metastatic disease received neoadjuvant chemotherapy. Two-surgeon scoring was performed in a blinded fashion using a validated scoring method. Patients with predictive index value scores less than 8 were offered primary surgery and those with scores 8 or greater received neoadjuvant chemotherapy. Univariate and multivariate analysis was performed for effects on progression-free survival. RESULTS: Six hundred twenty-one patients presenting with presumed advanced ovarian cancer were evaluated during the study period and 488 patients met inclusion criteria. Two hundred fifteen patients underwent laparoscopic scoring, of whom 125 had predictive index value scores less than 8 and 84 had predictive index value scores 8 or greater. Blinded two-surgeon predictive index value scoring resulted in bivariate discordance in only 2% of patients. Tumor cytoreduction led to no gross residual disease (R0 resection) in 88% of patients in the primary surgery group and 74% in the neoadjuvant chemotherapy group. Patients triaged to primary surgery had an improved progression-free survival of 21.4 months versus 12.9 months in those patients undergoing neoadjuvant chemotherapy (P<.001). Median progression-free survival by treatment group and residual disease status was as follows: primary surgery–R0 23.5 months; primary surgery–R1 (any gross residual disease) 17.6 months; neoadjuvant chemotherapy–R0 15.5 months; and neoadjuvant chemotherapy–R1 12.9 months (P<.001). On multivariate analysis for progression-free survival, baseline CA 125 (P=.001) and gross residual disease at tumor reductive surgery (P=.01) were significantly associated with progression-free survival. CONCLUSION: Laparoscopic triage assessment allowed for a personalized approach to the management of patients with advanced ovarian cancer and resulted in high complete surgical resection rates at tumor reductive surgery.