A short course of induction chemotherapy before chemoradiation significantly boosts survival outcomes in patients with locally advanced cervical cancer, and as such should be considered a new standard of care, researchers say.
Data from the UK-led INTERLACE trial, published in The Lancet, showed that induction chemotherapy led to a 40% reduction in the risk of death and a 35% cut in the risk of cancer recurrence over a follow-up period of at least five years.
According to the authors, the findings represent “the first published substantial overall survival improvement among patients with locally advanced cervical cancer since concomitant cisplatin over two decades ago”.
As such, “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,” they stressed.
The trial recruited 500 patients (median age 46) with locally advanced, unresectable cervical cancer over 10 years from 32 hospitals in the UK, Italy, Mexico, India and Brazil.
Patients randomly received either standard chemoradiation or an initial six-week course of induction chemotherapy (carboplatin and paclitaxel chemotherapy) followed by standard chemoradiation.
Five-year overall survival rates were 80% in patients who received the induction chemotherapy regimen versus 72% of those given standard care (HR of 0.60; p=0·015).
After a median follow-up of 67 months, five-year progression-free survival (PFS) rates were 72% versus 64%, respectively (HR 0.65; p=0·013).
The authors highlighted that haematological toxicity was more common with the induction regimen than the standard regimen as expected (grade 3-4; 30% versus 13%, respectively), and that this was was largely due to increased neutropenia (19% versus 5%).
However, the rate of non-haematological adverse events (grade 3-4) was similar between the treatment groups, at 44% versus 43%, respectively, they noted.
A key weakness of the trial was its extended duration, during which radiation techniques and doses were substantially modified making it “difficult to predict the ability to administer modern chemoradiotherapy after marrow-affecting induction chemotherapy”, said US gynaecologic oncologists Dr Linda Duska, University of Virginia School of Medicine, and Dr Leslie Randall, Inova Schar Cancer Institute, in a linked editorial.
Nevertheless, the “practice-changing” findings indicate that chemical cytoreduction is “feasible, tolerated and effective,” and “offers the opportunity for improvement in PFS and OS”, they stressed.
“This approach is a straightforward way to make a positive difference, using existing drugs that are cheap and already approved for use in patients,” added Dr Mary McCormack, lead investigator of the trial and Consultant Clinical Oncologist at UCLH.
“It has already been adopted by some cancer centres and there’s no reason that this shouldn’t be offered to all patients undergoing chemoradiation for this cancer,” she stressed.