Bradley Monk

PURPOSE: To determine factors and survival of patients with ovarian cancer after primary debulking surgery followed by adjuvant chemotherapy (PDS) versus neoadjuvant chemotherapy followed by interval cytoreduction (NAC). METHODS: GOG-262 was a prospective randomized trial evaluating once per week dose dense chemotherapy. The physicians were given the option of performing PDS versus NAC. Chi-squared tests and Kaplan-Meier procedures were used for analyses. RESULTS: Of 192 patients from centers offering both treatment options, 119 (62%) patients had PDS and 73 (38%) underwent NAC. Compared with the PDS group, NAC patients were older (60 years and older) age (67% v 47%; P < .01) and had more advanced (stage IV) disease (41.1% v 26.1%, P < .01) and peritoneal versus ovarian or fallopian tube cancers (16.4% v 5.0%, P < .001). The 5-year unadjusted overall survival of patients after NAC was 41.9 versus 47.8 months in the PDS group. After adjusting for prognostic factors, PDS was not an independent predictor for survival (hazard ratio [HR], 1.08 [95% CI, 0.67 to 1.7]; P = .75), whereas more advanced (IV v II/III)-stage (HR, 1.9 [95% CI, 0.93 to 3.89]; P = .079) and peritoneal versus ovarian or fallopian tube cancers (HR, 4.36 [95% CI, 1.45 to 13.1]; P = .009) were associated with poorer survival. CONCLUSION: Compared with primary surgery followed by chemotherapy, neoadjuvant chemotherapy followed by interval surgery patients were older and had more advanced disease (stage IV v II-III) and more primary peritoneal cancer ( v ovarian and fallopian tube cancer). The survival of these two groups was comparable after adjusting for prognostic factors.

PURPOSE: Frontline ovarian cancer treatment protocols involving bevacizumab, poly (ADP-ribose) polymerase inhibitors, and PD-1/PD-L1 inhibitors have failed to improve overall survival (OS) in patients with homologous recombination–proficient (HRP) tumors. To determine mechanistic mutation signatures associated with OS advantage, we constructed a whole-exome sequencing bioinformatic pipeline assay to analyze all 91 patients enrolled in the double-blind randomized placebo-controlled phase II VITAL trial. METHODS: We hypothesized that patients with stage IIIb-IV ovarian cancer who have HRP profile and high clonal tumor mutation burden (cTMB-H) will achieve greater response when undergoing maintenance therapy with gemogenovatucel-T. Our primary objective was assessment of OS using the Kaplan-Meier method among randomly assigned patients receiving either gemogenovatucel-T or placebo. RESULTS: The median OS in cTMB-H/HRP patients treated with gemogenovatucel-T was 68 months versus 19 months in those treated with placebo (hazard ratio [HR], 0.23; 95% CI, 0.06 to 0.83; 1-sided P = .008). The cTMB-H patients in the non-HRP group did not demonstrate OS advantage (HR, 0.99; 95% CI, 0.39 to 2.47; 1-sided P = .488). No grade 3 treatment-related toxicity was observed in the gemogenovatucel-T group with a follow-up of 8.4 years. CONCLUSION: These results demonstrate OS advantage for maintenance treatment of adult females with newly diagnosed, advanced stage IIIb-IV ovarian cancer with HRP status and cTMB-H profile who are in complete response after debulking surgery and frontline platinum-based doublet chemotherapy.

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