Neoadjuvant chemotherapy approach fails to improve locally advanced cervical cancer survival
medwireNews: Concomitant chemoradiation remains the standard of care for women with locally advanced squamous carcinoma of the cervix, following research showing no significant survival advantage with chemotherapy followed by surgery.
Concomitant chemoradiation has been the optimal treatment for patients presenting with stage IB2, IIA, or IIB cervical cancer for the past 2 decades based on high-quality trial evidence but approximately 25–40% of patients will relapse and die despite adequate treatment, said lead investigator Sudeep Gupta, from Tata Memorial Centre in Mumbai, India.
He explained to delegates at the ESMO 2017 Congress in Madrid, Spain, that patients in many parts of the world are treated with chemotherapy and then surgery despite the lack of a definitive comparison with chemoradiation.
An unexpected result.
Acknowledging that cervical cancer has shown a good response to platinum and taxane chemotherapy in the metastatic setting, Gupta et al tested the hypothesis that three cycles of neoadjuvant paclitaxel 175 mg/m2 plus carboplatin to an area under the concentration–time curve of 5–6 given before radical hysterectomy would improve patient survival compared with five cycles of cisplatin 40 mg/m2 plus standard pelvic radiation.
This strategy was based on neoadjuvant chemotherapy’s “ability to downstage disease, facilitate surgical resection and potentially eradicate systemic metastasis,” the presenter explained.
Due to slow accrual the trial successfully recruited only 633 of the planned 730 patients; patients were aged an average of 49 years and the majority (57.2%) had stage IIB disease.
After a median of 58.5 months, 5-year disease-free survival was achieved by 69.3% of the 316 patients randomly assigned to receive neoadjuvant chemotherapy and 76.7% of the 317 patients given concurrent chemoradiation, a significant difference in favor of concurrent chemoradiation.
However, 5-year rates of overall survival did not differ significantly between the two treatment arms, at 74.8% and 74.7%, respectively.
Subgroup analysis indicated that patients with stage IIB disease were the most likely to derive benefit from the concurrent chemoradiation therapy.
Treatment was generally well tolerated in both trial arms, Gupta said, with neoadjuvant chemotherapy arm patients experiencing a significantly higher rate of grade 3–4 thrombocytopenia within 42 days than the chemoradiation-treated patients but a lower rate of grade 1–2 symptoms such as diarrhea, dysuria, skin reactions, and renal toxicity.
After 3 months, concurrent chemoradiation was associated with higher rates of rectal, bladder, vaginal, and other toxicities than neoadjuvant chemotherapy but only vaginal toxicity remained significantly more common at 2 years.
“This trial has answered a long-standing therapeutic question in the treatment of patients with cervical cancer,” Gupta said.
He highlighted to the audience that although 71.8% of patients assigned to receive neoadjuvant treatment underwent the planned radical surgery, 21.5% crossed over to the concomitant chemoradiation arm, and a further 13.3% received adjuvant chemotherapy and 9.8% adjuvant radiation because of high-risk disease factors.
Thus, a “substantial minority” of patients assigned to receive neoadjuvant chemotherapy plus surgery arm received trimodality therapy, the presenter said.
“It is possible that delayed definitive treatment in this […] group of patients could be the reason for the outcome detriment in the surgical arm,” he remarked, with post hoc analysis supporting this hypothesis.
The researcher therefore concluded: “We suggest that neoadjuvant chemotherapy and surgery not be routinely practiced and that concomitant chemoradiation be the standard of care in this population.”
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