Data from the phase 3 INTERLACE trial reveals that incorporating short-course induction chemotherapy before chemoradiotherapy significantly boosts survival in patients battling locally advanced cervical cancer. The study highlights a clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS), potentially reshaping treatment paradigms for this patient population.
The INTERLACE trial (NCT01566240) randomly assigned 500 patients with locally advanced cervical cancer to either induction chemotherapy followed by chemoradiotherapy (n=250) or chemoradiotherapy alone (n=250). The induction chemotherapy regimen consisted of carboplatin (AUC 2) and paclitaxel (80 mg/m2) weekly for 6 weeks, followed by standard chemoradiotherapy. Chemoradiotherapy comprised external beam radiation therapy (EBRT) at 40.0 to 50.4 Gy in 20 to 28 fractions, with weekly cisplatin (40 mg/m2) for 5 weeks and brachytherapy.
Improved Survival Outcomes
The results demonstrated a significant improvement in PFS with the addition of induction chemotherapy. The 3-year PFS rate was 75% in the induction chemotherapy plus chemoradiotherapy group compared to 72% in the chemoradiotherapy alone group. At 5 years, the PFS rates were 72% and 64%, respectively (HR, 0.65; 95% CI, 0.46-0.9; P = .013). Overall survival also showed a notable increase. The 3-year OS rate was 85% with induction chemotherapy plus chemoradiotherapy versus 80% with chemoradiotherapy alone. The 5-year OS rates were 80% and 72%, respectively (HR, 0.60; 95% CI, 0.40-0.91; P = .015).
Adverse Events and Quality of Life
While the addition of induction chemotherapy led to improved survival outcomes, it was also associated with a higher incidence of grade 3/4 adverse events (AEs). In the induction chemotherapy plus chemoradiotherapy group, 59% of patients experienced grade 3/4 AEs, compared to 48% in the chemoradiotherapy alone group. Specifically, grade 3/4 hematological AEs were more frequent in the induction chemotherapy arm (30% vs. 13%). Anemia of grade 2 or higher was observed in 28% and 17% of patients, respectively. Neutropenia was the most common AE during the induction phase (7%). Quality of life was slightly lower in the induction chemotherapy group during the induction phase, but time to next anticancer therapy was improved.
Implications for Clinical Practice
The study authors advocate for considering this short-course induction chemotherapy regimen followed by chemoradiotherapy as a new standard of care for patients with locally advanced cervical cancer. "This short-course induction chemotherapy regimen followed within 7 days by chemoradiotherapy improves survival of patients with locally advanced cervical cancer," the authors wrote. "It should now be considered a standard of care and be included in the design of future trials that explore the incorporation of new agents for the treatment of locally advanced cervical cancer."
The researchers also emphasized the need for further studies to explore combination approaches in locally advanced cervical cancer.
