INTERLACE Trial: Induction Chemo in Cervical Cancer

For locally advanced cervical cancer, the standard treatment is chemoradiation. That means radiation to the pelvis given together with weekly cisplatin chemotherapy, followed by internal radiation called brachytherapy. It cures many people, but many still relapse with disease outside the pelvis. The INTERLACE trial asked a simple question. Does a short block of chemotherapy first — called induction chemotherapy — help more people survive? The answer, published in The Lancet in October 2024, was yes.

What the trial tested

INTERLACE was a randomized phase 3 trial run at 32 centers in Brazil, India, Italy, Mexico, and the UK. Between November 8, 2012, and November 17, 2022, it enrolled 500 adults, with 250 assigned to each group.

One group received standard chemoradiation alone. That meant cisplatin 40 mg/m² by vein once a week for 5 weeks — a protocol figure, not an instruction; any dose that applies to you is set by your own team. It also included external beam radiation of 45.0 to 50.4 Gy in 20 to 28 sessions, plus brachytherapy.

The other group first received 6 weeks of induction chemotherapy. Once a week, they got carboplatin (dosed to an AUC of 2) and paclitaxel 80 mg/m², both by vein. These are trial-protocol doses, not instructions — chemotherapy doses are always set by your own team. Chemoradiation then followed quickly. The median gap between induction and chemoradiation was just 7 days.

The drugs involved are older, widely available chemotherapy medicines, not new agents.

Exactly who the results cover

Everyone had locally advanced cervical cancer. In the trial's staging system (FIGO 2008), that meant stage IB1 disease with involved lymph nodes. It also included stages IB2, IIA, IIB, IIIB, and IVA. Most participants, 70%, had stage IIB tumors, and 11% had stage IIIB. Pelvic lymph nodes were positive in 43%.

These results do not describe early cervical cancers treated with surgery. They also do not describe cancer that has already spread to distant organs.

What the trial showed

After a median follow-up of 67 months, both of the trial's main endpoints favored induction chemotherapy.

• Progression-free survival: at 5 years, 72% of the induction group were alive without the cancer progressing. With chemoradiation alone, 64% were. The hazard ratio was 0.65.
• Overall survival: at 5 years, 80% of the induction group were alive, versus 72%. The hazard ratio was 0.60.

Overall survival is the endpoint that matters most, and this trial met it. More people were alive at 5 years, not just progression free.

Delivery of the plan was realistic, too. Of those assigned to induction, 92% completed at least 5 of the 6 weekly cycles. Chemoradiation still went ahead. In the induction group, 85% received 4 or more cisplatin doses. In the other group, 90% did.

Side effects

The added chemotherapy added toxicity. Severe adverse events, grade 3 or higher, occurred in 59% of the induction group. Without induction, the rate was 48%. The published abstract does not break these events down by type. A care team can explain what weekly carboplatin and paclitaxel usually involve.

The other recent advance: pembrolizumab

INTERLACE is not the only change in this setting. On January 12, 2024, the FDA approved pembrolizumab (Keytruda), an immunotherapy. It is given with chemoradiation for FIGO 2014 stage III-IVA cervical cancer. The KEYNOTE-A18 trial enrolled 1,060 patients. Among those with stage III-IVA disease, pembrolizumab lowered the relative risk of progression or death by 41% (hazard ratio 0.59). Overall survival data were not mature at that analysis. The two approaches were tested in separate trials, each against chemoradiation alone. No one yet knows how they compare or combine.

What to raise with the team

• What stage is my cancer under the FIGO system, and does it match the groups these trials enrolled?
• Would 6 weeks of induction carboplatin and paclitaxel before chemoradiation make sense for me? Can my center deliver it without delaying radiation?
• Am I a candidate for pembrolizumab with chemoradiation under the FDA-approved indication instead?
• How would either option change my side effects, visit schedule, and total treatment time?
• Are there clinical trials open to me in this setting?

What this does not mean

• It does not mean induction chemotherapy plus chemoradiation is right for every cervical cancer. The trial enrolled specific locally advanced stages.
• It does not mean the timing is flexible. In the trial, chemoradiation started a median of 7 days after induction ended. A long gap was not what was tested.
• It does not mean induction chemotherapy and pembrolizumab have been compared head to head. They have not.
• It does not guarantee an individual outcome. At 5 years, 72% of the chemoradiation-alone group were also still alive.

Sources

• PubMed: GCIG INTERLACE trial, Lancet 2024
• ClinicalTrials.gov: INTERLACE record (NCT01566240)
• FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer
• NCI: Cervical Cancer Treatment