KEY TAKEAWAYS
- The INTERLACE phase III trial aimed to evaluate the impact of a pre-radiation chemo protocol on survival and disease control in ACC patients.
- The primary endpoints were PFS and OS.
- The result demonstrated that adding chemo before radiation in ACC significantly extends cancer-free time and OS, making it a new SOC feasible across diverse healthcare settings.
Current treatment for locally advanced cervical cancer (LACC) involves chemoradiation therapy(CRT), but many patients still face recurrence and death. A smaller study showed promising results with a short course of CRT before standard treatment.
For this study, researchers aimed to evaluate the impact of a pre-radiation chemo protocol on survival and disease control in ACC patients.
Women eligible for the study had squamous, adeno, or adenosquamous carcinoma at FIGO (2008) stages IB1 with positive nodes, IB2, II, IIIB, or IVA. The randomization (1:1) assigned patients to either receive concurrent CRT alone (5 cycles of weekly cisplatin) or induction chemotherapy (IC) with carboplatin (6 weeks, AUC2) and paclitaxel (80mg/m2) followed by the same CRT in week 7.
A mandated minimum EQD2 dose of 78Gy to Point A was required, with 3D brachytherapy recommended. All participating centers underwent radiation quality assurance. The primary endpoints were progression-free survival (PFS) with (target HR 0.65) and overall survival (OS) (target HR 0.65-0.70).
About 500 patients were recruited from 32 centers across 5 countries, the median age was 46 years (range: 24-78). Stage distribution was as follows: IB1/2: 9%, II: 77%, IIIB: 11%, IVA: 3%. Node-negative and squamous subtypes were observed in 57% and 82% of cases. The arms were balanced, and 92% of neoadjuvant IC patients received 5/6 cycles of carboplatin/paclitaxel.
The median interval from IC to concurrent CRT was 7 days. In the CRT arm, 84% (IC/CRT) vs. 89% (CRT alone) had 4/5 cycles of cisplatin. Completion rates for external beam and brachytherapy were 92% and 89% in the CRT arm and 97% and 95% in the IC/CRT arm, respectively. The median overall treatment time for CRT was 45 days in both arms.
Grade ≥3 adverse events(AEs) were observed in 59% (IC/CRT) vs. 48% (CRT alone). The median follow-up was 64 months. The 5-year PFS rate was 73% with IC/CRT and 64% with CRT alone (HR 0.65; 95%CI: 0.46-0.91, P=0.013). The corresponding 5-year OS rates were 80% and 72% (HR 0.61; 95%CI: 0.40-0.91, P=0.04).
The result demonstrated that adding chemo before radiation in ACC significantly extends cancer-free time and OS, making it a new standard of care(SOC) feasible across diverse healthcare settings.
Clinical Trial: https://clinicaltrials.gov/study/NCT01566240
McCormack M, Gallardo Rincón D, Eminowicz G, Diez P, Farrelly L, Kent C, Hudson E, Panades M, Mathews T, Anand A, Persic M, Forrest J, Bhana R, Reed N, Drake A, Stobart H, Mukhopadhyay A, Hacker AM, Hackshaw A, Ledermann JA; GCIG INTERLACE Trial Collaborators. A Randomised Phase III Trial of Induction Chemotherapy Followed by Chemoradiation Compared with Chemoradiation Alone in Locally Advanced Cervical Cancer. Ann Oncol. 2023;34(suppl_2):S1254-S1335. doi:10.1016/annonc/annonc1358.
