In a phase II trial (NRG Oncology/GOG Study 279) reported in the Journal of Clinical Oncology, Horowitz et al found that concurrent cisplatin, gemcitabine, and intensity-modulated radiation therapy (IMRT) produced a high rate of complete pathologic response in patients with locally advanced vulvar squamous cell carcinoma not amenable to surgery.
Study Details
In the U.S. multicenter trial, 52 evaluable patients were enrolled between July 2012 and June 2015 and between July 2016 and February 2020. Prior to treatment, patients underwent inguinal-femoral lymphadenectomy or sentinel lymph node biopsy. Patients received concurrent cisplatin at 40 mg/m2 and gemcitabine at 50 mg/m2 once per week throughout IMRT with a maximum of 7 cycles; IMRT was given to the vulva at 64 Gy in 25 fractions and at 50 to 64 Gy to the groin/low pelvis if nodes in these regions were positive.
At 6 to 8 weeks after completing chemoradiation, patients underwent local core biopsies to assess pathologic response. Complete pathologic response was the primary endpoint; an improvement of 20% in complete pathologic response rate from the null hypothesis of 50% to 70% would support further investigation of the strategy.
Complete Pathologic Response Rate
Among the 52 patients with pathologic assessment, 38 (73%, 90% confidence interval [CI] = 61%–83%) achieved complete pathologic response, meeting the criterion for further assessment of the treatment strategy. No pelvic exenterations were performed.
At a median follow-up of 51 months, median progression-free survival was not reached, with a 12-month rate of 74% (90% CI = 62%–83%). Median overall survival was not reached, with a 24-month rate of 70% (90% CI = 57%–79%).
Adverse Events
Grade ≥ 3 adverse events occurred in 85% of patients. The most common grade 3 or 4 adverse events were leukopenia (52%), thrombocytopenia (38%), neutropenia (38%), anemia (38%, all grade 3), and radiation dermatitis (35%, all grade 3). One grade 5 event—sudden death–not otherwise specified—was reported and considered not likely related to treatment. At least one dose modification was required in 65% of patients.
The investigators concluded, “Weekly cisplatin and gemcitabine concurrent with IMRT sufficiently improved complete pathologic response in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.”
Neil S. Horowitz, MD, of Brigham and Women’s Hospital/Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Cancer Institute grants. For full disclosures of the study authors, visit ascopubs.org.
