LUGANO-MADRID – A 14-year randomised trial in more than 600 patients has concluded that chemoradiation should remain the standard treatment for patients with locally advanced cervical cancer. The findings are reported today at the ESMO 2017 Congress in Madrid. (1) The trial demonstrated no improved disease-free survival with neoadjuvant chemotherapy followed by surgery.
Chemoradiation, which refers to radiation delivered simultaneously with cisplatin-based chemotherapy, has been the standard treatment for patients with locally advanced cervical cancer since 1999 when it was shown to improve outcomes compared to radiation alone.
“Even with chemoradiation some patients relapse and die of their disease so there is a need for better treatments,” said first author Dr Sudeep Gupta, Medical Oncologist, Tata Memorial Centre, Mumbai, India. “Previous trials have found that neoadjuvant chemotherapy followed by surgery results in superior outcomes compared to radiation alone, but no trial has tested this strategy against standard treatment with chemoradiation.”
This trial examined whether neoadjuvant chemotherapy followed by surgical removal of the tumour could improve outcomes in patients with locally advanced cervical cancer compared to standard treatment with chemoradiation.
The trial included 633 patients with stage IB2, IIA or IIB squamous cell cervical cancer who were randomised to either neoadjuvant chemotherapy (paclitaxel and carboplatin) followed by radical hysterectomy or chemoradiation (standard pelvic radiation plus cisplatin). The primary endpoint was disease-free survival which was defined as survival without relapse or death due to cancer.
After a median follow-up of 58.5 months, the primary endpoint occurred in 30% of patients in the chemotherapy/surgery group and 23% of patients in the chemoradiation group. The corresponding five-year disease-free survival rates were 69.3% in the chemotherapy/surgery group and 76.7% in the chemoradiation group (p = 0.038).
“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 five years than those who received standard treatment with chemoradiation.”
When the researchers included death due to any cause in the definition of disease-free survival, they found no significant difference between the two treatment groups although there was a trend towards increased disease-free survival with chemoradiation. There was no statistically significant difference in overall survival between the two groups.
Gupta said: “Chemoradiation should continue to be the standard treatment for patients with locally advanced cervical cancer.”
Commenting on the results for ESMO, Dr Sandro Pignata, Director, Uro-Gynaecological Department, Istituto Nazionale Tumori IRCCS "Foundation G. Pascale”, Naples, Italy, said: “This is the first direct comparison between these two strategies and it shows that chemoradiation should remain the standard treatment.”
“Cervical cancer is caused by infection with human papilloma virus (HPV) and can be prevented with vaccination and screening,” he continued. “As a result, the incidence of locally advanced cervical cancer is decreasing in Europe but is still high in developing countries, where modern radiation therapy may not be available. In these situations, neoadjuvant chemotherapy followed by surgery may still be the best option.”
Pignata pointed out that an ongoing European Organisation for Research and Treatment of Cancer (EORTC) trial will be the second study comparing chemoradiation with neoadjuvant chemotherapy followed by surgery. He said: “When the EORTC trial has completed, a combined analysis of the two studies may provide further insights into the most effective treatment for locally advanced cervical cancer.”
Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress
- Abstract 928O_PR - ‘Neoadjuvant chemotherapy followed by surgery (NACT-surgery) versus concurrent cisplatin and radiation therapy (CTRT) in patients with stage IB2 to IIB squamous carcinoma of cervix: A randomized controlled trial (RCT)’ will be presented by Dr Sudeep Gupta during Presidential Symposium II on Sunday, 10 September, 16:30 to 18:00 (CEST), in Madrid Auditorium.
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
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Neoadjuvant chemotherapy followed by surgery (NACT-surgery) versus concurrent cisplatin and radiation therapy (CTRT) in patients with stage IB2 to IIB squamous carcinoma of cervix: A randomized controlled trial (RCT)
S. Gupta1, P. Parab1, R. Kerkar2, U. Mahantshetty3, A. Maheshwari2, S. Sastri3, R. Engineer3, R. Hawaldar4, J. Ghosh1, S. Gulia1, S. Godbole1, N. Kumar2, J. Malliga2, R. Dalvi1, Y. Kembhavi1, M. Gaikar1, R. Ranade2, H. Tongaonkar2, R. Badwe5, S. Shrivastava3
1Medical Oncology, Tata Memorial Centre, Mumbai/INDIA, 2Gynecologic Oncology, Tata Memorial Centre, Mumbai/INDIA, 3Radiation Oncology, Tata Memorial Centre, Mumbai/INDIA, 4Biostatistics, Tata Memorial Centre, Mumbai/INDIA, 5Surgical Oncology, Tata Memorial Centre, Mumbai/INDIA
Background: The standard treatment for locally advanced cervical cancer is CTRT. We tested in a RCT whether outcomes could be improved by NACT-surgery.
Methods: Patients with clinical stages IB2, IIA or IIB squamous cervical cancer were randomized (stratified on stage) to either NACT-surgery arm comprising 3 cycles of paclitaxel (175 mg/m2) and carboplatin (AUC 5-6) every 3 weeks followed by radical hysterectomy or CTRT arm comprising standard pelvic radiation with 5 cycles of cisplatin (40 mg/m2) once per week. Post-operative radiation was given as per protocol criteria. Primary end point was disease-free survival (DFS, relapse or death whichever earlier) while secondary end points were overall survival (OS) and toxicity. The trial was designed to demonstrate 10% absolute increase in 5-year DFS in NACT-surgery arm, assuming 65% DFS in CTRT (control) arm (2-sided α=0.05, power=80%) with planned sample size of 730.
Results: Trial accrual was stopped after 635 patients were randomized between September 2003 and February 2015, of whom there were 2 eligibility violations. In remaining 633 (316 NACT-surgery, 317 CTRT, intent-to-treat population) there were 113 (17.9%) IB2, 158 (25.0%) IIA and 362 (57.2%) stage IIB patients. The arms were balanced for stage, age, haemoglobin, performance status and radiological pelvic lymph node status. At time of analysis (data cut-off 30 March 2017) median follow-up was 58.5 months; number of DFS events and deaths in NACT-surgery arm were 105 and 80 and those in CTRT arm were 87 and 80, respectively. There was no significant difference between NACT-surgery and CTRT with respect to 5-year DFS (67.5% vs. 72.2%, respectively, hazard ratio [HR] = 1.299, 95% CI 0.977-1.725, P=0.07) and 5-year OS (74.8% vs. 74.7%, respectively, HR = 1.025, 95% CI 0.752-1.398, P=0.87). NACT-surgery was not superior to CTRT in DFS and OS after adjusting for prognostic factors. Toxicity in two arms was acceptable with some differences in pattern.
Conclusions: Neoadjuvant chemotherapy followed by radical surgery is not superior to cisplatin based concurrent chemoradiation in locally advanced squamous carcinoma of cervix.
Clinical trial identification: ClinicalTrials.gov number NCT00193739
Keyword: Neoadjuvant, chemotherapy, Chemoradiation, cervix
Funding: Department of Atomic Energy-Clinical Trials Unit, Tata Memorial Centre, Mumbai
Disclosure: All authors have declared no conflicts of interest.