Chemoradiotherapy Remains Standard of Care in Cervical Cancer

Liam Davenport

September 11, 2017

MADRID ― Patients with locally advanced cervical cancer should continue to be treated with chemoradiotherapy and not be initially offered chemotherapy alone followed by radical surgery, conclude Indian researchers who compared the two approaches in a randomized controlled trial.

For the past 20 years, the standard of care in locally advanced cervical cancer has been radiotherapy and simultaneous treatment with cisplatin (Platinol, HQ Specialty.

However, up to 40% of women experience a relapse following treatment, prompting interest in neoadjuvant chemotherapy followed by radical surgery (NACT-surgery), particularly because older trials that compared the more invasive approach with radiotherapy alone yielded positive results.

However, the new trial, which included more than 600 cervical cancer patients, showed that, during a 5-year period, NACT-surgery was associated with a significant increase of almost 40% in rates of relapse or death vs standard chemoradiotherapy.

The study was presented by Sudeep Gupta, MD, PhD, professor of medical oncology, Tata Memorial Center, Mumbai, India, during a presidential symposium here at the European Society for Medical Oncology (ESMO) 2017 Congress.

Dr Sudeep Gupta

At a press conference regarding the study, Dr Gupta said: "Chemotherapy followed by surgery is not superior to radiotherapy and simultaneous chemotherapy in patients with locally advanced cervical cancer...and should not be routinely practiced."

Noting that this is the first completed study to compare the two treatment approaches, he added: "This a robust trial with 625 patients, and we believe that these data are definitive."

Dr Gupta pointed out that another trial on the same approach is currently underway. That trial is being conducted by the European Organization for Research and Treatment of Cancer (EORTC), using a slightly different chemotherapy backbone.

He also highlighted that India and Europe differ with respect to the prevalence of cervical cancer subtypes. Squamous carcinoma of the cervix is the predominant subtype in India, whereas adenocarcinoma is the most common subtype in Europe.

Dr Gupta said, however: "I don't have enough reasons to believe that the results would be different if adenomacarcinoma was also included in the trial."

Our data suggest that concomitant chemoradiation should continue to be standard of care. Dr Sudeep Gupta

"We believe that our data suggest that concomitant chemoradiation should continue to be standard of care," he concluded.

Dr Markus Joerger

Press conference chair Markus Joerger, MD, PhD, assistant professor of medical oncology and clinical pharmacology at St. Gallen Cancer Center, Switzerland, said that, prior to the current study, it had not been "clear whether chemotherapy followed by surgery would be superior to chemoradiotherapy.

"I think we all agree that it has been confirmed as the standard of care at the moment," he commented. He added that the results of the EORTC study are due to be reported in 2019.

Study Details

The study included patients with squamous cell carcinoma of stage IB2, IIA, or IIB whose ECOG performance status was 0-1. The patients were stratified by stage and were randomly assigned in a 1:1 ratio to receive NACT-surgery (n = 317) or chemoradiotherapy (n = 318).

Neoadjuvant chemotherapy consisted of paclitaxel (multiple brands) plus carboplatin (Paraplatin, Corden Pharma) administered every 3 weeks for three cycles. In the chemoradiotherapy arm, patients received cisplatin once a week for 5 weeks in conjunction with external-beam radiotherapy plus high-dose-rate brachytherapy.

Patients who did not respond to neoadjuvant chemotherapy after two or three cycles could cross over to chemoradiotherapy without undergoing surgery.

The team noted that the treatment arms were well balanced in terms of stage, age, hemoglobin levels, body mass index, performance status, and radiologic pelvic lymph node status. The median age of the patients was 49 years.

Following neoadjuvant chemotherapy, 71.8% of those assigned to NACT-surgery went on to have radical surgery; the remaining 28.2% were switched over to chemoradiotherapy.

Overall, the median follow-up period was 58.8 months.

The 5-year disease-free survival rate on intention-to-treat analysis was 69.3% among patients assigned to NACT-surgery vs 76.7% for patients treated with chemoradiotherapy.

The researchers calculated that among patients treated with NACT-surgery, the risk for relapse or death due to cancer was significantly worse than among patients who received chemoradiotherapy (hazard ratio [HR], 1.38; P = .038).

Subgroup analysis suggested that women with stage 2B disease in particular experienced a significant benefit in disease-free survival with chemoradiotherapy compared with patients who received NACT-surgery. This difference appeared to account for the overall outcomes benefit.

There were no significant differences in overall survival between the two treatment groups (HR, 1.03).

The team reported that, although chemoradiotherapy was associated with higher 90-day rates of adverse events than NACT-surgery, there were no significant differences between the groups in 2-year rates of toxicity of any grade at rectal sites (P = .474), bladder sites (P = .204), and other sites (P = .334).

However, NACT-surgery was associated with a significant reduction in the 2-year vaginal toxicity rate, at 12.0% vs 25.6% with chemoradiotherapy (P < .001).

High Burden of Disease in Developing World

Study discussant Domenica Lorusso, MD, PhD, Gynecology Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, emphasized that the burden of cervical cancer and the majority of deaths attributable to the disease are greater in the developing world.

She observed that neoadjuvant chemotherapy followed by surgery emerged in countries where chemoradiotherapy was not available and has subsequently been acknowledged as an alternative to chemoradiotherapy in guidelines.

Dr Lorusso said that the slow accrual rate and the early stopping of the current trial limit interpretation of its results. It is possible that chemoradiotherapy "overperformed" in comparison with the surgical approach, owing to the use of suboptimal neoadjuvant chemotherapy.

She also noted that progression-free survival may not have been the best choice of primary endpoint, because it is a surrogate marker of outcomes.

Summarizing, Dr Lorusso said that "concucrrent chemoradiation remains the standard of care" in locally advanced cervical cancer, "but I strongly suggest" waiting for the results of the EORTC trial "before putting the tombstone" on NACT-surgery, because it remains an important option in several indications, as well as in developing countries.

The study was funded by the Clinical Trials Unit of the Department of Atomic Energy, Tata Memorial Center, Mumbai. No relevant financial relationships have been disclosed.

European Society for Medical Oncology (ESMO) 2017 Congress. Abstract 928O_PR, presented September 10, 2017.


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