KEY TAKEAWAYS
- The phase II trial aimed to assess the efficacy of adding pembro to cis-RT in vulvar cancer patients.
- The primary endpoint was ORR.
- Pembro with cis-RT in vulvar cancer showed no unexpected side effects; an ongoing study awaits further data on resistance mechanisms and efficacy.
Vulvar cancer, a rare gynecologic cancer with a rising incidence, often requires surgery and chemoradiation for local/regional cases, while systemic chemotherapy and immunotherapy are options for distant metastases. Unresectable or metastatic cases in gynecologic cancers generally pose poorer outcomes, and the combination of cisplatin and radiation (cis-RT) demonstrates both cytotoxic and immunomodulatory effects.
Oladapo Yeku and his research team conducted a study that aimed to investigate the efficacy and safety of adding pembrolizumab (pembro) to cis-RT in the management of vulvar cancer.
Eligible patients with primary unresectable, incompletely resected, recurrent, or metastatic vulvar squamous cell carcinoma undergoing RT included those who had prior chemotherapy or immunotherapy. Treatment involved weekly cisplatin (40 mg/m2) concurrently with RT and pembro (200 mg) administered every three weeks for 12 cycles. The primary endpoint was objective response rate (ORR), with a secondary objective of 6-month recurrence-free survival (RFS). Additionally, serum cytokines and HMGB-1 were assessed.
About 15 patients were enrolled, with 14 evaluable. All patients experienced any grade adverse events (AE), with 78.6% encountering Grade 3 AEs, predominantly related to cisplatin. No Grade 4 or higher AEs occurred, but one serious AE (Grade 3 acute kidney injury related to cis) was reported. Grade 3 neutropenia and Grade 3 ALT increases were observed in 28.6% and 7.1% of patients, respectively.
Common treatment-emergent adverse events (TEAE) included anemia (78.6%), diarrhea (78.6%), nausea (78.6%), fatigue (78.6%), and thrombocytopenia (50%). Pembro-related AEs (n = 18) were all Grade 1, except for Grade 2 nephrotic syndrome (9%) and Grade 2 hypothyroidism (14%) in 1 and 2 patients, respectively. Patients with progressive disease showed elevated serum levels of CCL4, CCL11, and CXCL12 at cycle 3.
The interim analysis revealed no unexpected adverse events with concurrent cisplatin-based radiation therapy and pembrolizumab, and ongoing cytokine analysis may provide insights into resistance mechanisms, marking the pioneering evaluation of this combination in vulvar cancer with a targeted enrollment of 24 patients. Research is sponsored by Massachusetts General Hospital.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT04430699.
Yeku OO. et al. (2023) ‘’Interim safety analysis of a phase 2 trial of cisplatin-sensitized radiation therapy and pembrolizumab for unresectable vulvar cancer.’’ Presented at ESMO I-O 2023 (102P).
