Professor Christine Gennigens, a distinguished medical oncologist at CHU de Liège, has provided an in-depth overview of the GCIG INTERLACE trial, which was presented during the presidential session at the ESMO congress.
The INTERLACE trial represents a pivotal phase 3 randomised study conducted in patients who have locally advanced cervical cancer. Inclusion criteria encompassed patients with squamous, adenocarcinoma or adenosquamous carcinoma, adhering to the FIGO (2008) staging system at stages IB1 (node-positive), IB2, II, IIIB, and IVA. These patients were randomly assigned in a 1:1 ratio to receive either chemoradiotherapy alone (involving five cycles of weekly cisplatin) or an induction chemotherapy phase followed by the same chemoradiotherapy regimen in week 7. The trial boasted a median follow-up duration of 64 months.
To maintain a treatment window of a maximum of 50 days, adherence to this stipulation was mandatory. The primary endpoints consisted of PFS and OS, utilising a hierarchical design, where the analysis of PFS took precedence. If statistical significance was achieved, an analysis of OS followed. Baseline characteristics exhibited a well-balanced distribution across both treatment arms: roughly 70% of patients had FIGO IIB, 80% displayed squamous histology, and approximately 57-58% were node-negative. Remarkably, high adherence was observed for the neoadjuvant treatment, with 84% of patients in both arms successfully completing the six cycles of chemotherapy. Notably, concerning cisplatin adherence, 79% of patients in the arm without neoadjuvant chemotherapy versus 68% in the arm with chemotherapy managed to complete the required five cycles of cisplatin.
Results revealed that the neoadjuvant chemotherapy arm exhibited a favourable PFS at five years, with a median PFS of 73%, compared to 64% in the chemoradiotherapy-alone arm (HR: 0.65; 95% CI: 0.46-0.91, p=0.013). Furthermore, five-year OS rates were reported as 80% and 72%, respectively (HR: 0.61; 95% CI: 0.40-0.91, p=0.04).
Notably, the occurrence of total local or pelvic relapses remained similar between both treatment arms (16%). However, patients who did not receive neoadjuvant chemotherapy exhibited a higher incidence of distant metastasis (20% versus 12%).
The adverse events analysis revealed that grade ≥3 adverse events were encountered in 59% of patients receiving induction chemotherapy along with chemoradiotherapy, while 48% of patients receiving chemoradiotherapy alone experienced such events. Haematological toxicity was more pronounced in the neoadjuvant arm, although no significant disparities were observed in non-haematological toxicity.
Professor Gennigens concluded her overview by highlighting the significance of the INTERLACE trial’s positive outcomes. Since 1999, when the addition of chemotherapy to radiotherapy was introduced, no positive phase 3 trial had been reported in locally advanced cervical cancer until the advent of INTERLACE and the KEYNOTE-A18 study at the ESMO congress. The apparently contradictory results between the positive INTERLACE trial and the OUTBACK trial, where adjuvant chemotherapy after standard chemoradiation for women with locally advanced cervical cancer did not demonstrate benefits, underscore the rationale for neoadjuvant chemotherapy. The future application of this schedule, based on the 2018 FIGO classification, is crucial for defining which patients will benefit from the INTERLACE approach. Importantly, this treatment regimen is poised to be widely adopted, even in resource-constrained healthcare settings.
McCormack M- A randomised phase III trial of induction chemotherapy followed by chemoradiation compared with chemoradiation alone in locally advanced cervical cancer. The GCIG INTERLACE trial. ESMO 2023 – LBA8
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