Induction chemo plus CRT improves PFS and OS vs CRT alone in locally advanced cervical cancer

The international, multicentre, randomized phase III GCIG INTERLACE trial reports significantly higher 5-year progression-free survival (PFS) and overall survival (OS) rates with induction chemotherapy followed by chemoradiotherapy (CRT) vs CRT alone in patients with locally advanced cervical cancer.

The standard of care for locally advanced cervical cancer is cisplatin-based CRT, which is curative in approximately three-quarters of cases. [N Engl J Med 1999;340:1144-1153] However, many patients still relapse and die from metastatic disease. [J Clin Oncol 2008;26:5802-5812]

“Overall, chemotherapy regimens with shorter cycle duration and higher platinum dose intensity [are] associated with improved outcomes,” wrote the INTERLACE investigators. “We conducted a single-arm multicentre phase II trial [CXII study], which showed a high tumour response rate with neoadjuvant short-course once-a-week carboplatin and paclitaxel. This helped design the INTERLACE trial.” [Br J Cancer 2013;108:2464-2469]

Patients with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB or IVA disease) were randomly assigned to the CRT alone group (n=250; once-a-week intravenous cisplatin 40 mg/m² for 5 weeks with 45.0–50.4 Gy external beam radiotherapy delivered in 20–28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78–86 Gy) or the induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m² for 6 weeks) plus CRT group (induction group; n=250). Median interval between induction chemotherapy and CRT was 7 days. [Lancet 2024;404:1525-1535]

After a median follow-up of 67 months, 5-year PFS rates were 72 percent in the induction group and 64 percent in the CRT alone group, with a hazard ratio (HR) of 0.65 (95 percent confidence interval [CI], 0.46–0.91; p=0.013), while the respective 5-year OS rates were 80 and 72 percent, with an HR of 0.60 (95 percent CI, 0.40–0.91; p=0.015). “These findings represent the first published substantial OS improvement among patients with locally advanced cervical cancer since concomitant cisplatin more than two decades ago,” commented the investigators.

“[Furthermore,] the [induction chemotherapy] drugs are cheap and widely available. Therefore, this approach can be readily adopted in all healthcare settings,” they added. “Induction chemotherapy delivered according to the INTERLACE protocol should be included in clinical guidelines as an option to improve outcomes in patients with locally advanced cervical cancer.”

Adverse events (AEs) of any grade occurred in 99 percent of patients in the induction group and 97 percent of patients in the CRT alone group. Grade 3–4 events were reported in 59 and 48 percent of patients in the induction and CRT alone groups, respectively. Grade 3–4 haematological AEs were more common in the induction vs CRT alone group (30 vs 13 percent), while rates of nonhaematological grade 3–4 AEs were similar in both groups. “Importantly, infection rates were similar in both groups,” noted the investigators.

Grade 3–4 vaginal toxicity was only seen in two patients during induction chemotherapy, and there was no difference in all-grade vaginal bleeding between the two groups. “We therefore do not believe vaginal bleeding should be a contraindication for [induction chemotherapy],” remarked the investigators.