To date, cervical cancer remains a major global health issue.¹ In 2020, there were 604,000 newly diagnosed cases and 324,000 deaths, 90% of which occurred in low- and middle-income countries.¹ Chemoradiation therapy (CRT) has been considered the standard of care (SOC) in locally advanced diseases for over two decades.¹ Newer radiotherapy techniques, radiation doses, and treatment durations have improved local control, but areas of improvement remain in the relapse and death rate of metastatic disease.¹ During the ESMO Congress 2023, Professor Mary McCormack presented the results of the INTERLACE trial, a randomized phase 3 trial that compared induction chemotherapy (IC) followed by CRT with CRT alone in treating locally advanced cervical cancer.¹

A total of 500 patients who were newly diagnosed with stages IB1 node-positive, IB2, II, IIIB, IVA squamous, adeno, and adenosquamous cervical cancer deemed eligible for IC and CRT were recruited and randomized to receive either 6 weeks of IC (paclitaxel and carboplatin) + 5 weeks of CRT (n=250) or 5 weeks of CRT alone (n=250).¹ Baseline characteristics were similar between the two groups.¹ Median age was 46 years in both arms and the majority of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (88%), had stage II disease (75%), and squamous cell tumor (82%).¹  The treatment groups were followed up 3-monthly for 2 years, then 6-monthly for 5 years after treatment initiation. The primary endpoints were progression-free survival (PFS) and overall survival (OS).¹ Secondary endpoints included the incidence of adverse events (AEs), patterns of relapse, quality of life (QoL), and time to subsequent treatment.¹

The results demonstrated that IC + CRT led to a significant risk reduction in disease progression when compared to CRT alone (HR=0.65; 95% CI: 0.46-0.91; p=0.013), contributing to relatively higher 3-year (75% vs. 72%) and 5-year (73% vs. 64%) PFS rates in the IC + CRT group.¹ Similarly, OS was significantly longer in the IC + CRT group compared with the CRT group (HR=0.61; 95% CI: 0.40-0.91; p=0.04), with slightly higher 3-year (86% vs. 80%) and 5-year (80% vs. 72%) OS rates observed in the IC + CRT group.¹ Moreover, the total local and pelvic relapses were equal in both arms (16%), while the total distant relapses were higher in the CRT group than in the IC + CRT group.¹

The combined treatment with IC and CRT was shown to be tolerable among patients, as evidenced by their adherence rates. 84% of patients in the IC + CRT group completed the 6 weekly cycles of IC, while 68% of patients completed the entire treatment regimen.¹ In terms of AEs, most patients in both treatment groups experienced AEs at some point during the treatment (IC + CRT vs. CRT: 99% vs.  95%).¹ However, Grade 3 or 4 AEs were more frequently observed in the IC + CRT arm compared to the CRT arm (59% vs. 48%), with the incidence of any-grade hematological AEs in the IC + CRT arm being more than double that in the CRT arm (30% vs. 13%).¹

In conclusion, at 5 years after treatment, IC+CRT was capable of inducing a 9% improvement in the PFS rate and an 8% improvement in the OS rate compared to CRT monotherapy.¹ The adherence to IC + CRT therapy was high and its safety profile was comparable to that of CRT monotherapy.¹ Therefore, IC with weekly paclitaxel and carboplatin delivered immediately after CRT may be considered the new SOC in treating patients with locally advanced cervical cancer.¹