In patients with newly diagnosed, locally advanced cervical cancer, induction chemotherapy prior to chemoradiation therapy led to a 35% reduction in the risk for disease recurrence or death (hazard ratio [HR] = 0.65; P = .013) and a 39% reduction in the survival hazard (HR = 0.61; P = .04), investigators from the GCIG INTERLACE trial reported in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2023.¹

Mary McCormack, MBBS, PhD

“INTERLACE met both its primary endpoints. Induction chemotherapy prior to chemoradiation led to a 9% [absolute] improvement in the progression-free survival rate and an 8% improvement in overall survival rate at 5 years,” said Mary McCormack, MBBS, PhD, a clinical oncologist at University College Hospital, London. “Induction chemotherapy with weekly paclitaxel and carboplatin delivered immediately before chemoradiotherapy should be considered the new standard in locally advanced cervical cancer and is feasible across diverse health-care settings.”

At 5 years, the progression-free survival rate was 73%, and the overall survival rate was 80% with induction chemotherapy prior to chemoradiotherapy, compared with rates of 64% and 72%, respectively, with chemoradiotherapy alone. The difference led to a hazard ratio (HR) of 0.65 (P = .013) for progression-free survival and 0.61 (P = .04) for overall survival.

“This is the first phase III randomized trial in locally advanced cervical cancer to show a survival benefit in over 2 decades,” observed the study’s invited discussant Krishnansu Tewari, MD, Associate Professor in the Division of Gynecologic Oncology at the University of California, Irvine. “Importantly, this study used drugs that are readily available, and physicians taking care of these patients could consider induction chemotherapy with carboplatin and weekly paclitaxel tomorrow morning…. This regimen can be readily adopted in low-resource regions.”

INTERLACE Details

From 2012 to 2022, the study enrolled 500 patients with stage IB1/II to IVA cervical carcinoma across 32 centers in the United Kingdom, Mexico, India, Italy, and Brazil. Most patients (82%) had squamous cell histology, and 58% had node-negative disease.

Patients were randomly assigned to receive induction chemotherapy with carboplatin and paclitaxel given weekly for 6 weeks, followed by standard chemoradiotherapy with cisplatin for 5 weeks and external-beam radiotherapy (40–50.4 Gy in 20–28 fractions and brachytherapy to give for a minimum total equivalent dose of 78 Gy to point A). Median chemoradiotherapy time was 45 days in each arm. Approximately 60% of patients received three-dimensional (3D) conformal radiotherapy, and around 80% received 3D brachytherapy.

Adherence to induction chemotherapy was good; 84% completed six weekly cycles, and 92% completed five weekly cycles. Cisplatin adherence rates in those given induction/chemoradiotherapy and chemoradiotherapy alone were 85% and 90%, respectively, for at least four weekly cycles and 68% and 79%, respectively, for five weekly cycles. Adherence rates to radiotherapy were also very high—97% in the experimental arm and 92% with chemoradiotherapy alone.

Median follow-up was 64 months. At 3 years, for the experimental arm vs the standard chemoradiotherapy arm, the progression-free survival rate was 75% vs 72%; at 5 years, it was 73% vs 64%, respectively. For overall survival, the 3-year rate was 86% vs 80%, and the 5-year rate was 80% vs 72%.

“Most patients experienced an adverse event at some point during treatment, as expected. There were, however, three deaths within 30 days of completing treatment in the standard arm and one in the experimental arm attributable to a combination of sepsis and thromboembolic events,” Dr. McCormack reported.

As anticipated, hematologic toxicities were more frequent in the experimental arm—30% vs 13%—mostly from neutropenia, “but this did not compromise the delivery of radiotherapy,” she said. Nonhematologic adverse events were similar in the arms. 

DISCLOSURE: Dr. McCormack has served on advisory boards for GSK, Eisai, and AstraZeneca; and as a coordinating principal investigator for Roche. Dr. Tewari reported financial relationships with AbbVie, AstraZeneca, Eisai, GSK, ImmunoGen, Karyopharm, Merck, Morphotek, Regeneron, Roche/Genentech, and Seagen/Genmab.

REFERENCE

1. McCormack M, Gallardo D, Eminowicz, et al: A randomised phase III trial of induction chemotherapy followed by chemoradiation compared with chemoradiation alone in locally advanced cervical cancerl. ESMO Congress 2023. Abstract LBA8. Presented October 22, 2023.