ESMO: Trials end 20-year hiatus in cervical cancer therapy

Amid all the new high-tech therapies on display at the ESMO cancer conference, a study funded by Cancer Research UK has shown what can be achieved with cheap generic drugs used in a better way.

The INTERLACE trial focused on women being treated for newly diagnosed, locally advanced cervical cancer (LACC), a group ordinarily treated with a combination of chemo and brachytherapy known as chemoradiation (CRT), but which has a high risk of relapsing and dying from metastatic disease.

The 500-subject study explored the use of an additional six-week induction course of carboplatin and paclitaxel chemotherapy given before CRT, and generated impressive results – improving progression-free survival (PFS) and overall survival (OS) by 35% and 39%, respectively, compared to CRT alone.

After five years of follow-up, 80% of women who received the more intensive treatment were still alive, compared to 72% of a group that received CRT alone. Meanwhile, PFS was 73% and 64%, respectively, showing the additional regimen reduced the risk of death or the cancer returning.

The new regimen, given once a week in the build-up to CRT, should be considered a “new standard of care” and is “feasible across diverse healthcare settings,” according to Dr Mary McCormack of University College Hospital in the UK, who presented the results at ESMO.

ESMO discussant Professor Ana Oaknin of the Hospital Universitari Vall d’Hebron in Spain commented that the results are “encouraging for a disease that for several decades has failed to show improvements in long-term outcomes beyond those achieved with CRT alone and that has a high unmet need for new treatments.”

One factor that needs to be considered is that quite a high proportion of women in the study had LACC that had not moved to the lymph nodes – 58% – so, would be considered at lower risk of relapse.

“Further analysis, in terms of nodal status, would be useful in determining the suitability of the induction chemotherapy approach for different relapse risk groups,” said Oaknin.

The additional side-effect burden posed by the intensive induction regimen is another consideration for patients and their doctors.

Immunotherapy finally has an impact

INTERLACE, meanwhile, wasn’t the only study presented at ESMO that showed improved outcomes in newly diagnosed LACC.

The KEYNOTE-A18 study looked at the combination of CRT with MSD’s PD-1 inhibitor Keytruda (pembrolizumab) and found a 30% improvement in PFS compared to CRT plus placebo, as well as a trend towards an improvement in OS after a median follow-up of around 18 months.

ESMO discussant Professor Bradley Monk of the University of Arizona College of Medicine called the results “very exciting” and in stark contrast to the phase 3 CALLA trial of AstraZeneca’s PD-L1 inhibitor Imfinzi (durvalumab) plus CRT – reported at last year’s meeting – which generated disappointing results.

“It is unclear why the KEYNOTE-A18 study was positive when CALLA was negative, but it could be due to differences in sample size or because the patients in KEYNOTE-A18 were a higher-risk population,” said Monk.

“Minor differences in the mechanism of action between PD-1 and PD-L1 inhibitors may also account for differences in efficacy,” he suggested.

Cervical cancer is one of the most common tumour types in women, with 14,500 new cases diagnosed every year in the US and 4,300 deaths.