1. Goodwin, Peter M.

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MADRID-Chemoradiation was clearly shown to be superior to a combination of neoadjuvant chemotherapy plus surgery for patients with locally-advanced cervical cancer in a 14-year randomized trial in more than 600 patients reported at the ESMO 2017 Congress (Abstract 928O_PR).

cervical cancer; ESM... - Click to enlarge in new windowcervical cancer; ESMO 2017 Congress. cervical cancer; ESMO 2017 Congress

"Neoadjuvant chemotherapy and surgery is not an appropriate option for women with locally-advanced cervical cancer. Concomitant chemoradiation should continue to be the standard of care," noted Sudeep Gupta, MD, DM, Professor of Medical Oncology at the Tata Memorial Centre in Mumbai, India, who said the study was originally set up to compare these two approaches because they had thought surgery following chemotherapy could outperform the standard of care.


The new data implied that chemoradiation was the treatment of choice. And even though some countries had limited availability of radiotherapy services, this could no longer be considered a factor in the choice of treatment, Gupta said. The difference in efficacy clearly clinched that.

Sudeep Gupta, MD, DM... - Click to enlarge in new windowSudeep Gupta, MD, DM. Sudeep Gupta, MD, DM

"Our data suggests that a lack of radiation facilities is not a good enough reason to deny women the standard treatment of concomitant radiation," he said.


"Even with chemoradiation, some patients relapse and die of their disease, so there is a need for better treatments," stated Gupta. Previous trials had found that neoadjuvant chemotherapy followed by surgery resulted in superior outcomes compared to radiation alone. But no trial had tested this strategy against standard treatment with chemoradiation.


Study Results

The study randomized 633 patients with stage IB2, IIA, or IIB squamous cell cervical cancer to either neoadjuvant chemotherapy (paclitaxel plus carboplatin) followed by radical hysterectomy or chemoradiation (standard pelvic radiation plus cisplatin). The primary endpoint was disease-free survival (DFS), relapse, or death. Secondary endpoints were overall survival and toxicity.


After a median follow-up of 58.5 months, 30 percent of patients assigned to chemotherapy with surgery had recurrences or died compared with 23 percent of patients in the chemoradiation group. The 5-year DFS rates were 69.3 percent in patients treated with chemotherapy plus surgery and 76.7 percent in those randomized to chemoradiation (p = 0.038), equivalent to a 38 percent increased risk of relapse of death in patients randomized to surgery-the opposite of what the investigators had expected when they began the study.


"We found the reverse of our hypothesis was true," said Gupta. "Patients who received chemotherapy followed by surgery were less likely to be alive and disease-free at 5 years than those who received standard treatment with chemoradiation."


When the researchers included death due to any cause in the definition of DFS, they found no significant difference between the two treatment groups, although there was a trend toward increased DFS with chemoradiation. No statistically-significant difference in overall survival between the two groups has yet emerged.


Chemoradiation as Standard

Sandro Pignata, MD, PhD, Director of the Uro-Gynecological Department at Istituto Nazionale Tumori "Fondazione G. Pascale" in Naples, Italy, said: "This is the first direct comparison between these two strategies and it shows that chemoradiation should remain the standard treatment."


But he emphasized the need for prevention. "Cervical cancer is caused by infection with HPV and can be prevented with vaccination and screening," he said, noting the incidence of locally-advanced cervical cancer was decreasing in Europe.


Pignata looked forward to data from an ongoing European Organisation for Research and Treatment of Cancer trial also comparing chemoradiation with neoadjuvant chemotherapy followed by surgery. "A combined analysis of the two studies may provide further insights into the most effective treatment for locally advanced cervical cancer," he noted.


But for Gupta, the negative finding from the Indian study was already enough to prompt a search for other solutions. "Perhaps in the future it is time to look forward to targeted therapies and immunotherapy to improve the outcome of cervical cancer patients a little further," he concluded.


Peter M. Goodwin is a contributing writer.


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