Induction chemotherapy before CRT ups survival in locally advanced cervical cancer

Induction chemotherapy followed by chemoradiotherapy (CRT) significantly improves progression-free survival (PFS) and overall survival (OS) in patients with locally advanced cervical cancer compared with standard CRT alone, according to the INTERLACE trial presented at ESMO 2023.

“The INTERLACE trial met both its primary endpoints [of improving PFS and OS at 5 years in patients with locally advanced cervical cancer],” said lead author Dr Mary McCormack from the University College London Hospitals NHS Trust in London, UK.

At a median follow-up of 64 months, patients who received induction chemotherapy + CRT had a significant improvement in PFS, with a 35-percent reduction in the risk of death (hazard ratio [HR], 0.65; p=0.013), compared with those treated with standard CRT alone.

Similarly, OS was significantly improved in the combination therapy arm than the standard CRT alone arm (HR, 0.61; p=0.04).

Moreover, the 5-year PFS and OS rates were significantly improved by 73 percent and 80 percent, respectively, with induction chemotherapy + CRT vs 64 percent and 72 percent with CRT alone. [ESMO 2023, abstract LBA8]

With regard to patterns of relapse, the incidence of the total and local pelvic relapses was similar between the induction chemotherapy + CRT and standard CRT alone arms (16 percent for both). However, the total distant relapses were more common in the standard of care arm vs the experimental arm (20 percent vs 12 percent), indicating that “this short course of chemotherapy has reduced distant relapse,” McCormack noted.

Grade 3–4 adverse events (AEs) occurred more frequently in the induction chemotherapy + CRT group than the CRT alone group (59 percent vs 48 percent). Haematological AEs were also higher with the combination arm vs the CRT alone arm (30 percent vs 13 percent), but a similar incidence of non-haematological AEs was observed in both treatment arms (44 percent vs 43 percent).

“As anticipated, haematological toxicity was greater in the experimental arm, but this did not compromise the delivery of radiotherapy,” noted McCormack.

This phase III trial analysed 500 patients (median age 46 years) with locally advanced cervical cancer, of whom 75 percent had stage II disease and 82 percent had squamous cell tumours at baseline. Participants were randomly assigned in a 1:1 ratio to either induction chemotherapy (carboplatin AUC 2 and paclitaxel 80 mg/m² given weekly for 6 weeks), followed immediately with standard CRT* at week 7, or standard CRT alone.

“We developed an induction chemotherapy protocol using weekly paclitaxel and carboplatin followed within 7 days by CRT,” said McCormack. “[Overall, results showed that this protocol] led to a 9-percent improvement in the PFS rate and an 8-percent improvement in the OS rate at 5 years.”

“Therefore, induction chemotherapy with weekly paclitaxel and carboplatin delivered immediately before CRT should be considered the new standard in locally advanced cervical cancer and is feasible across diverse healthcare settings,” she added.