medwireNews: Phase III trial findings demonstrate a significant gain in disease-free survival (DFS) and overall survival (OS) with concurrent cisplatin and radiotherapy (CT-RT) versus radiation alone for women with Federation of Gynecology and Obstetrics stage IIIB cervical cancer.
“Our study demonstrates that concurrent weekly cisplatin-based CT-RT should be considered as the preferred standard of care in patients with stage IIIB squamous cell carcinoma of the uterine cervix”, say Umesh Mahantshetty, from Tata Memorial Hospital in Mumbai, India, and colleagues.
“This study provides level 1 evidence in the largest clinical trial reported so far in favor of concurrent weekly cisplatin chemotherapy in this setting”, they write in JAMA Oncology.
The open-label trial included 850 women who were randomly assigned to receive CT-RT, consisting of external beam RT (50 Gy in 25 fractions over 5 weeks), brachytherapy and weekly cisplatin 40 mg/m2, or to receive RT plus brachytherapy alone. After a median of 88 months, the 424 women given CT-RT had a 5-year DFS rate of 52.3%, which was significantly higher than the 43.8% achieved by the 426 patients using only RT. The hazard ratio (HR) for disease relapse or death was 0.81.
Five-year OS was also significantly higher with CT-RT than RT alone, at 54% versus 46% and a HR for death of 0.82. And both DFS and OS remained significantly higher with CT-RT after taking into consideration confounding factors such as age, tumour size and RT dose, the researchers report.
CT-RT was associated with higher rates of grade 3 and 4 adverse events, including neutropenia and thrombocytopenia, but there were no cases of febrile neutropenia or bleeding. Late adverse events were comparable in the two trial arms except for a higher rate of rectosigmoid events with CT-RT than RT (6.8 vs 4.5%).
The authors of an accompanying comment describe the study findings as “remarkable” for addressing the “important global clinical dilemma” caused by lack of statistical power to demonstrate a significant survival benefit with CT-RT for stage IIIB–IVA patients in earlier studies, leading to its underuse in some low- and middle-income countries despite being considered the optimal strategy.
Acknowledging that optimal resource allocation in such countries was a key question for the study investigators, Akila Viswanathan, from Johns Hopkins Medicine in Baltimore, Maryland, USA, and co-authors note that the concurrent strategy was associated with “modestly higher” rates of acute toxicity and “did not result in prolongation of treatment time”.
They suggest that concurrent CT-RT with cisplatin given every 3 weeks might be “an alternative more feasible and potentially effective solution in low-resource settings.”
Shrivastava S, Mahantshetty U, Engineer R, et al. Cisplatin chemoradiotherapy vs radiotherapy in FIGO stage IIIB squamous cell carcinoma of the uterine cervix. A randomized clinical trial. JAMA Oncol; Advance online publication 8 February 2018. doi:10.1001/jamaoncol.2017.5179
Nwachukwu CR, Mayadev J, Viswanathan AN. Concurrent chemoradiotherapy for stage IIIB cervical cancer – global impact through power. JAMA Oncol; Advance online publication 8 February 2018. doi:10.1001/jamaoncol.2017.5078
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