by ecancer reporter Clare Sansom

The work presented at the NCRI conference on Tuesday 3 November included a 'showcase' of recent results from four large clinical trials.

Firstly, Hisham Mehanna from the University of Birmingham described PET-NECK, a Phase III trial comparing PET CT guided active surveillance with planned neck dissection to remove lymph nodes in head and neck squamous cell carcinoma (HNSCC).

This is one of the largest surgical trials in this tumour type in the world.

Patients in the active surveillance (intervention) arm only received surgery if there was evidence of persistent nodal disease on PET CT  following chemotherapy.

A total of 564 patients with HNSCC, 75% of whom were p16 positive (indicating HPV infection) were recruited and randomised equally to the control and intervention arms.

No significant difference in overall or disease free survival was observed for the whole cohort, or for subgroups stratified by p16 status.

Patients in the guided surveillance arm had similar quality of life but underwent fewer surgical procedures and had fewer adverse events; this regimen was also significantly more cost-effective.

Mehanna concluded by recommending that active surveillance should become the routine treatment for this indication.

James Larkin from the Royal Marsden Hospital in London then presented results from CheckMate 067, a Phase III trial comparing nivolumab and nivolumab plus ipilimumab with ipilimumab alone in treatment-naive patients with advanced melanoma.

Results from Phase I and Phase II studies have suggested that the action of these two antibodies is complementary.

A total of 945 patients were randomised 1:1:1 to receive either nivolumab, ipilimumab or both drugs, with ilipmumab as the control arm: the trial was not powered to compare nivolumab with the combination.

Both progression free and overall survival were taken as primary endpoints; the patients are still being followed up for overall survival.

Median progression free survival was 11.5 months in the combination arm, 6.9 months in the nivolumab arm and 2.9 months in the ipilimumab arm.

This represented a statistically significant improvement between either of the regimens containing nivolumab and ipilimumab, and benefit was seen in all subgroups tested including those with the poorest predicted prognosis.

Adverse events were common but most resolved within weeks, and the remaining side effects could be controlled easily with medication.

A large number of patients – up to 38% in the combination arm – discontinued treatment early on due to adverse events, but, interestingly, many of these patients continued to respond.

Larkin concluded by highlighting the benefits of nivolumab and particularly the combination over ipilimumab alone in this indication, at least for progression free survival.

Hormone therapy has been the mainstay of prostate cancer treatment for many decades; it is very often effective for a time but men with metastatic or advanced disease invariably relapse.

The STAMPEDE trial is a multi-arm, multi-stage trial designed to assess the addition of other agents to base hormone therapy in this indication

Patients were recruited between 2005 and 2015 and data is now being analysed.

Nicholas James from the University of Warwick presented the first overall survival results, involving the addition of docetaxel, zoledronic acid or both drugs to long-term hormone therapy in men receiving this for the first time.

A total of 2,962 patients with metastatic or high-risk locally advanced disease were recruited and randomised 2:1;1:1 to receive the standard of care (hormone therapy) or this plus either or both of the control drugs.

The primary outcome measure was overall survival; secondary outcomes were failure-free survival and toxicity.

A marked survival benefit was seen in the docetaxel arm, with a hazard ratio of 0.76 and an increase in median survival time from 67 months with standard of care to 77 with the addition of docetaxel.

In contrast, zoledonic acid did not improve survival times either on its own or in addition to docetaxel.

Grade 3 and 4 toxicity was relatively high but well controlled in all arms.

James concluded by suggesting that docetaxel should be added to the standard treatment regimens for men with metastatic or high risk prostate cancer starting hormone therapy.

Finally, Simon Crabb from the University of Southampton presented results from a Phase II/III trial of lapatinib as maintenance therapy for metastatic bladder cancer.

Metastatic transitional cell carcinoma (TCC) of the bladder has a poor prognosis, with no treatments after first-line chemotherapy showing clinical benefit.

A significant proportion of these cancers over-express the HER1 or HER2 receptors, which are inhibited by lapatinib.

This trial was established to show whether lapatinib used as maintenance therapy after first-line chemotherapy could extend progression free survival in HER1 and/or HER2 positive metastatic bladder TCC.

A total of 455 patients were screened for HER1 and HER2 over-expression and the 232 patients positive for one or both receptors were randomised to receive either lapatinib or placebo after chemotherapy, with the primary endpoint progression free survival.

Median progression free survival was 4.6 months in the lapatinib arm and 5.3 months in the control arm; this small difference in favour of the control was not statistically significant.

No significant difference was observed between HER1 and HER2 positive patients, or between the patients with the highest expression levels of these receptors and others.

Crabb concluded that maintenance therapy with this drug did not improve outcomes for this difficult to treat group of patients.