Neoadjuvant chemo and surgery no better than CRT for locally advanced cervical cancer
Researchers from the Tata Memorial Centre in Mumbai, India, compared the two treatment strategies in 633 treatment-naïve patients with stage IB2, IIA or IIB squamous cell carcinoma of the cervix who had no distant metastases. The results, presented at the European Society for Medical Oncology (ESMO) 2017 Congress held in Madrid, Spain, showed significantly lower 5-year DFS rates in patients randomized to receive NACT (paclitaxel and carboplatin) followed by surgery compared with those who received CRT (standard pelvic radiation plus cisplatin). [ESMO 2017, abstract 928O_PR]
“At 5 years, DFS rate was 69.3 percent in the NACT/surgery group vs 76.7 percent in the CRT group [hazard ratio (HR), 1.38; p=0.038],” said investigator Dr Sudeep Gupta of the Tata Memorial Centre, who presented the results. “When we performed an additional analysis of DFS that included all-cause mortality, 5-year DFS rate was 67.5 vs 72.2 percent [HR, 1.30; p=0.07].”
“A subgroup analysis showed that the main benefit of CRT was in patients with stage IIB disease. In these patients, CRT offered a significant DFS advantage over NACT followed by surgery [p=0.04],” Gupta added. “In patients with stage IB2 or IIA disease, however, the two treatment strategies did not differ significantly in terms of DFS.”
OS, a secondary endpoint of the trial, did not differ significantly between the groups (HR, 1.025; p=0.87).
Treatment was generally well tolerated in both groups. No significant between-group differences were found in acute toxicities during or within 42 days after treatment, except for a higher rate of thrombocytopenia in the NACT/surgery group (grade 3/4, 3.5 percent vs 0.3 percent for CRT; p=0.003).
More than 90 days after completion of treatment, patients in the CRT group were found to have higher rates of any-grade rectal (13.3 vs 5.7 percent; p=0.002), bladder (7.3 vs 2.8 percent; p=0.017) and vaginal (36.9 vs 19.9 percent; p<0.001) toxicities than those in the NACT/surgery group.
Notably, the rate of vaginal toxicity remained high in the CRT group more than 24 months after completion of treatment, affecting 25.6 percent of patients compared with 12 percent of those in the NACT/surgery group (p<0.001).
“Based on these results, CRT should remain the standard of care in locally advanced cervical cancer. NACT followed by surgery should not be routinely practiced,” concluded Gupta.
“In resource-limited countries where radiotherapy is not widely accessible, NACT followed by surgery may remain a treatment option for locally advanced cervical cancer,” said discussant Dr Domenica Lorusso of the Istituto Nazionale dei Tumori in Milan, Italy. “Furthermore, when pregnancy is a priority for the patient, data support the use of NACT in the second trimester without compromise on maternal or foetal outcome. Data also support NACT followed by fertility-sparing surgery as an option for fertility preservation.”
“The ongoing OUTBACK and INTERLACE trials will evaluate the role of chemotherapy before or after CRT in locally advanced cervical cancer,” Lorusso added.