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TAMPA, Fla. -- More than 70% of patients with unresectable, locally advanced vulvar carcinoma had complete responses to chemoradiation with intensity-modulated radiation therapy (IMRT), according to a prospective study reported here.

IMRT plus cisplatin-gemcitabine chemotherapy resulted in clinical complete response (CCR) in 71.2% of patients and complete pathologic response (CPR) in 73.1%. After a median follow-up exceeding 4 years, median progression-free (PFS) and overall survival (OS) had yet to be reached.

The response rates compared favorably with historical data showing CCR rates of 48%-64% and CPR rates of 31%-50%, reported Neil Horowitz, MD, of Dana-Farber Cancer Institute in Boston, at the Society of Gynecologic Oncology meeting.

"Compared to historical controls, the addition of gemcitabine and weekly cisplatin to IMRT significantly improved complete pathologic response rates in women with locally advanced, unresectable squamous cell carcinoma of the vulva," he said.

Vulvar squamous cell carcinoma is uncommon, affecting an estimated 6,400 women in the U.S. each year. Locally advanced disease is difficult to define in the absence of standardized staging criteria. Historically, exenterative procedures often formed the basis for treatment, resulting in substantial morbidity and disfigurement, Horowitz noted.

Two Gynecologic Oncology Group trials ( and GOG 205) changed the standard of care for locally advanced vulvar cancer to cisplatin-based chemoradiation. In GOG 101, a third of patients achieved CPR and only 4% required urinary or bowel diversion procedures with cisplatin-5FU chemotherapy. GOG 205 combined a higher dose of radiation with weekly cisplatin and omitted 5FU, which led to a CPR rate of 50%, and no patient required urinary or bowel diversion, said Horowitz.

Investigators in GOG 279 sought to build on the results of GOG 101 and GOG 205 by adding gemcitabine to weekly cisplatin and delivering a higher dose of radiation with IMRT. The study had the objective of increasing the CPR rate from 50% in GOG 205 to 70%, which would be considered clinically interesting and warranting further investigation.

The phase II trial was conducted in two stages. If at least 15 of 27 patients achieved CPR during the first stage, enrollment would continue to a target accrual in the range of 45 to 52 patients.

Investigators enrolled 57 patients, 52 of whom proved to be eligible and were treated. The patients had a median age of 58, median tumor size 5 cm, and 100% squamous cell carcinoma. Horowitz said 42% of the patients had stage II disease, 35% had stage III, and 23% had stage IV.

The patients (both stages combined) received a median of six cycles of chemotherapy. Compliance with the IMRT protocol was acceptable in 63.5% and had minor violations in 21%. Compliance was not reviewed in the remaining cases. Ultimately, nine patients (17.3%) could not be evaluated for CPR because of a lack of biopsy.

The most common grade 3 adverse events (AEs) were anemia (20 patients), leukopenia (19), neutropenia (14), thrombocytopenia (13), and radiation dermatitis (18). Grade 4 toxicity included eight cases of leukopenia, seven of thrombocytopenia, and six of neutropenia.

The data showed substantial improvement in outcomes versus GOG 101 and GOG 205: CCR of 71.2% versus 48% and 64%, respectively; CPR of 73.1% versus 31% and 50%; and 12-month PFS of 74% versus 70% in GOG 205. After a median follow-up of 51 months, patients in GOG 279 had a 24-month OS of 69.6%.

Horowitz acknowledged several limitations of the trial, as well as unanswered questions. The explanation for the improved CCR and CPR is unclear: the addition of gemcitabine or use of IMRT, which resulted in a 13% increase in the radiation dose. HPV infection status was unclear, raising the question of whether the results apply to HPV- and HPV+ disease.

Treatment paradigms have changed since the trial began in 2012, with the introduction of targeted therapy and immunotherapy. Finally, 94% of the study population was Caucasian, raising a question about generalizability.

Additionally, the unknown response status for the patients who did not have post-treatment biopsies creates uncertainty regarding the true treatment effect.

"If we assume that all nine patients had a complete clinical response -- and that was the reason they didn't have a biopsy or resection -- it's possible that the complete pathologic response rate could be as high as 90.4%," said Horowitz.

Although grade 3/4 toxicity was high with concurrent chemotherapy and IMRT, the improvements in complete clinical and pathologic responses may have resulted from radiation dose escalation to 64 Gy compared to the prior dose of 57.6 Gy in GOG205, said Akila Viswanathan, MD, director of radiation oncology and radiation molecular sciences at Johns Hopkins in Baltimore. Though not statistically significant, the PFS improved from 70% in GOG205 to 74% in the current study.

"A future study may warrant assessment of additional radiation dose escalation to 70 Gy, as this is given at present in many practices and may demonstrate additional benefit," Viswanathan, a clinical expert for the American Society for Radiation Oncology, told 番茄社区app via email. "The question of whether another concurrent chemotherapy or immunotherapy agent may be less toxic also remains to be answered."

This story has been updated to include comments from Viswanathan.

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