A win for gemcitabine plus cisplatin and intensity-modulated radiotherapy in vulvar cancer

The use of gemcitabine concurrently with cisplatin and intensity-modulated radiation therapy (IMRT) appears to improve response and prolong progression-free survival (PFS) in women with locally advanced vulvar cancer not amenable to surgical resection, according to the results of the phase II NRG Oncology Trial 279 (NRG-GOG-0279) presented at SGO 2023.

Over a median follow-up of 51 months, most of the patients in the study achieved complete pathological response (73.1 percent, 90 percent confidence interval [CI], 61.2–83.0) and complete clinical response (71.2 percent, 90 percent CI, 59.1–81.3) with the regimen, reported lead study investigator Dr Neil Horowitz of the Brigham and Women’s Hospital and Harvard Medical School. [SGO 2023, abstract 16]

The PFS rate at 12 months was 74 percent (90 percent CI, 62.2–82.7), while the overall survival rate at 24 months was 69.6 percent (90 percent CI, 57.4–79).

In terms of safety, grade 3 and 4 adverse events (AEs) occurred in 48 percent and 34 percent of patients. One patient experienced grade 5 toxicity. Frequently reported grade 3/4 AEs included radiation dermatitis (34.6 percent), leukopenia (51.9 percent), thrombocytopenia (38.5 percent), and electrolyte abnormalities (28.8 percent). A single grade 5 toxicity event occurred 1 day after cycle 4. 

“Women with locally advanced vulvar cancer are currently treated with standard chemoradiation, which results in a high number of patients experiencing locoregional recurrence in their lifetime,” said Horowitz.

“NRG-GOG-0279 was designed to determine whether the addition of gemcitabine to cisplatin and higher doses of radiation administered with IMRT, could improve the efficacy of the treatment while avoiding added toxicity for these patients,” Horowitz continued.

The findings, according to Horowitz, provide evidence that the regimen helps improve survival and response outcomes for women with locally advanced vulvar cancer not amenable to surgical resection.

Then again, “the regimen may be limited by its toxicity,” he acknowledged.

NRG-GOG-0279 enrolled 57 patients, of which three never received treatment and two were ineligible after central path review. The median age of the patients was 58 years, and 94 percent were Caucasian. Patients with stage II (42 percent), III (35 percent), and IV (23 percent) disease had squamous histology, and the median tumour size was 5 cm.

Overall, the patients received a median of 6 cycles of gemcitabine and cisplatin. IMRT quality review showed that 84.7 percent of plans were of high quality, while 21.2 percent had minor variations in radiation. All patients were prescribed the full protocol dose. A total of 8 percent of patients withdrew from the trial due to toxicity, and 6 percent refused additional therapy.

“Locoregional recurrence after standard chemoradiation remains high in locally advanced vulvar cancer,” Horowitz said. “Further investigation is warranted to find an ideal regimen for this difficult-to-treat patient population.”