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Induction chemotherapy before chemoradiotherapy in locally advanced cervical cancer

In INTERLACE, a randomised phase 3 study, 6 weeks of carboplatin and paclitaxel immediately before standard chemoradiotherapy was associated with improved progression-free and overall survival in women with locally advanced cervical cancer.

  • Mary McCormack, PhD; Gemma Eminowicz, MD; Dolores Gallardo, MD; Patricia Diez, MSc; Laura Farrelly, MSc; Christopher Kent, FRCR; et al.

  • October 14, 2024

  • The Lancet
  • Volume 404, Issue 10462, Pages 1525–1535
  • 10.1016/S0140-6736(24)01438-7

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Evidence before this study

We searched PubMed for clinical trials and systematic reviews published in English between Jan 1, 2003, and March 1, 2024, that assessed induction chemotherapy in patients with cervical cancer, using the terms “cervical or cervix cancer”, “induction chemotherapy”, or “neoadjuvant chemotherapy”. Induction chemotherapy was associated with variable efficacy in locally advanced cervical cancer, which was influenced by study design. Two large trials evaluating neoadjuvant chemotherapy before surgery and standard chemoradiotherapy did not show improvements in survival. Many previous studies did not minimise the time interval between finishing neoadjuvant chemotherapy and definitive radiation, chemoradiotherapy, or surgery. Overall, chemotherapy regimens with shorter cycle duration and higher platinum dose intensity were associated with improved outcomes. We had conducted a single arm multicentre phase 2 trial (CXII study) which showed a high tumour response rate using neoadjuvant short-course once-a-week carboplatin and paclitaxel, and this was used to help design the INTERLACE trial.

Added value of this study

The results of INTERLACE show that a short course of chemotherapy using 6 weeks of carboplatin and paclitaxel immediately before standard chemoradiotherapy provided a clinically meaningful and statistically significant improvement in both progression-free survival and overall survival in women with locally advanced cervical cancer. The drugs are cheap and widely available and therefore this approach can be readily adopted in all health-care settings. This is the first randomised phase 3 study to show a significant survival advantage with the addition of induction chemotherapy before chemoradiotherapy in locally advanced cervical cancer. Although chemoradiotherapy is curative treatment for about 75% of patients (80% in INTERLACE), increasing this by 7–10% (at 3–5 years) represents a clinically meaningful improvement and at a relatively low cost.

Implications of all the available evidence

Induction chemotherapy delivered according to the INTERLACE protocol should be included in clinical guidelines as an option to improve outcomes in patients with locally advanced cervical cancer. This approach could be included in the design of future clinical trials of immunotherapy or other targeted drugs in the front-line setting. The study findings presented here also refute the perception that chemotherapy administered before radiotherapy or chemoradiotherapy is detrimental to outcome.

Source: The Lancet

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