Short-induction chemotherapy improves survival in advanced cervical cancer

The addition of 6 cycles of carboplatin/paclitaxel induction chemotherapy, directly followed by standard chemoradiotherapy, improved progression-free survival (PFS) and overall survival (OS) in participants with locally advanced cervical cancer by almost 40%, results of the phase 3 INTERLACE trial showed.

For more than 2 decades, chemoradiotherapy followed by brachytherapy has been the standard of care for patients with locally advanced cervical cancer (FIGO IB3–IVA). Although the local control of disease has increased over time, up to 30% of patients eventually relapse and die from metastatic disease. A recent phase 2 study showed the feasibility and a good response rate of induction chemotherapy using weekly paclitaxel and carboplatin for 6 cycles, immediately followed by standard chemoradiotherapy [1].

The current phase 3 INTERLACE trial (EudraCT: 2011-001300-35) randomised 500 participants with locally advanced cervical cancer (stage IB1 node positive–IVA) to standard chemoradiotherapy or induction chemotherapy followed by standard chemoradiotherapy. The primary endpoints were PFS and OS. Results were presented by Dr Mary McCormack (University College London, UK) [2].

About 75% of enrolled participants presented with stage IIA or IIB disease, 82% showed squamous histology and almost 60% of participants and tumours were node-negative. The adherence to induction chemotherapy was high, with more than 90% of participants having received at least 5 cycles of induction chemotherapy. Also, more than 90% of participants adhered to radiotherapy in both study arms. Induction chemotherapy substantially increased both PFS and OS. At the 5-year follow-up, 73% of participants in the induction arm were progression-free versus 64% in the control arm (HR 0.65; 95% CI 0.46–0.91; P=0.013). At the same follow-up time point, 86% of participants in the induction arm were still alive versus 80% in the control arm (HR 0.61; 95% CI 0.40–0.91; P=0.04, see Figure). “OS in the control arm was similar to that in the recent literature,” remarked Dr McCormack. Total local relapse rates after 5 years were 16% in both arms. In contrast, the total distant relapse rate after 5 years was 12% in the induction arm versus 20% in the control arm.

Figure: Overall survival results from the INTERLACE trial over time [2]



CI, confidence interval; CRT, chemoradiotherapy; FU, follow-up; HR, hazard ratio;  OS, overall survival; Yr, year.  

“In conclusion, the INTERLACE trial showed that short induction chemotherapy with paclitaxel and carboplatin can significantly improve PFS and OS and decrease distant relapses. This induction protocol is feasible across different healthcare settings and should be considered the new standard in locally advanced cervical cancer,” summarised Dr McCormack.

1. 
   
   1. McCormack M, et al. Br J Cancer. 2013;108:2464–2469.
   2. McCormack M, et al. A randomised phase III trial of induction chemotherapy followed by chemoradiation compared with chemoradiation alone in locally advanced cervical cancer: The GCIG INTERLACE trial. Abstract LBA8, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 19 December, 202319 December, 2023