medwireNews: Cisplatin chemoradiotherapy (CRT) significantly delays disease recurrence and improves survival compared with radiotherapy (RT) alone in women with stage IIIB squamous cell carcinoma of the cervix, phase III study data show.
The results provide “level 1 evidence in the largest clinical trial reported so far in favor of concurrent weekly cisplatin chemotherapy in this setting,” Umesh Mahantshetty (Homi Bhabha National Institute, Mumbai, India) and co-investigators remark.
Between July 2003 and September 2011, 850 women with FIGO stage IIIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either weekly cisplatin (40 mg/m2 per week) plus a combination of external beam RT (50 Gy in 25 fractions over 5 weeks) and brachytherapy or the RT/brachytherapy regimen alone.
During a median 88 months of follow-up, there were 222 recurrences and 213 deaths among the 424 women in the CRT arm, and 252 recurrences and 243 deaths among the 426 women in the RT arm.
As reported in JAMA Oncology, the 5-year disease-free survival (DFS) rate was significantly higher with CRT than with RT, at 52.3% versus 43.8%, and an unadjusted hazard ratio (HR) for relapse or death of 0.81.
The overall survival rate (OS) rate at 5 years was also significantly higher among the women who received CRT than among those who received RT, at 54% versus 46%, and an unadjusted HR of 0.82.
And the associations were not attenuated after adjustment for prognostic factors such as age, tumor size, parametrial invasion, pretreatment hemoglobin level, RT dose, and overall treatment time, with HRs of 0.81 for both outcomes.
The researchers note that there was a higher rate of grade 3 or 4 neutropenia and thrombocytopenia in the CRT arm than in the RT arm, but there was no febrile neutropenia or bleeding.
Mahantshetty and co-authors say that “[a]lthough the results of previous trials have suggested a benefit of concurrent chemotherapy, the findings have been less than definitive in stage IIIB because of concerns about sample size, chemotherapy regimen and schedule, RT doses, variable use of brachytherapy, and treatment time.”
The large sample size, homogeneous patient population, long-term follow-up period, and simple concurrent chemotherapy regimen used in the current study allowed the team to conclude that “concurrent weekly cisplatin-based [CRT] should be considered as the preferred standard of care” for this patient population.
Akila Viswanathan (Sidney Kimmel Cancer Center, Baltimore, Maryland, USA) et al agree with this conclusion in an accompanying commentary. They say that the study “provides definitive evidence for concurrent CRT to treat patients with stage IIIB cervical cancer in LMICs [low- and middle-income countries].”
But the commentators add that “[a]n unspoken tragedy is written into [this trial]: hundreds, if not thousands, of women globally have died over the past 2 decades because of the limited adoption of the overarching significant results of concurrent chemotherapy shown in multiple prior randomized trials in cervical cancer.”
They continue: “Given such strong numbers showing a survival advantage, albeit without the statistical significance, was it necessary to increase the power to prove what was a foregone conclusion?
“Cervical cancer disproportionately affects poor women without insurance. The cost of their care is a dilemma facing many LMICs, and it is in response to the unforeseen cost of chemotherapy that an RT-only trial was allowed to open and accrue.”
By Laura Cowen
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