Highlights from day three, afternoon session, of the 2013 NCRI Cancer Conference

6 Nov 2013

by ecancer reporter Clare Sansom

The second part of the Clinical Trials Showcase featured results from recent Phase III trials in Hodgkin's lymphoma and ovarian cancer.

Early stage Hodgkin's lymphoma is easily treated with chemo- and radiotherapy with an excellent prognosis, but there are concerns about long term toxicity particularly as the disease is common in teenagers and young adults.

Sparing patients radiotherapy where possible is likely to reduce long-term toxicity, but predicting which patients need it is challenging.

John Radford of the University of Manchester presented results from the RAPID trial in which patients with Stage IA or IIA Hodgkin's lymphoma were given PET scans after three cycles of chemotherapy.

Patients with detectable residual disease were given one more chemotherapy cycle plus radiotherapy, and those without were randomised to receive either no further treatment or radiotherapy alone.

After three years, progression free survival was 97% in the radiotherapy arm and 90.7% for those patients given no further treatment.

This small improvement in progression free survival with radiotherapy is insufficient to prove the statistical inferiority of no further treatment.

These results were first presented at an American Society of Haematology meeting in December 2012 and have already led to changes in clinical practice.

Jonathan Ledermann from the UCL Cancer Trials Centre, London, presented results from the ICON6 trial of the oral VEGF receptor tyrosine kinase inhibitor cediranib in relapsed platinum-sensitive ovarian cancer.

Patients were randomised into three arms, and all received a further six cycles of platinum-based chemotherapy. Patients in arm A received placebo during this treatment and afterwards; those in arm B received cediranib during chemotherapy and were then switched to placebo; and those in arm C received cediranib throughout.

The results showed a significant advantage of 3.2 months in progression free and 2.7 months in overall survival between arms A and C, with the results for arm B close to those for arm C.

Adverse events were rather more common in patients receiving cediranib, but these were manageable.

These results indicate that VEGFR inhibitors such as cediranib are promising options for ovarian cancer, at least in patients with platinum-sensitive tumours.

Clinical trials – a dizzying number of clinical trials – also featured In Tuesday's second plenary lecture, given by Frances Shepherd of Princess Margaret Hospital and the University of Toronto, Canada.

Shepherd subtitled her talk on the classification of genetic pathways and mutations in non-small cell lung cancer (NSCLC) “It's not quite as simple as we once thought”, referring to the increasing complexity of the mutation landscape in this disease.

Much of her talk focused on mutations in KRAS and EGFR, genes that are commonly mutated in NSCLC.

She described many large studies that have not reproduced the early results associating KRAS mutations with poor prognosis.

It is now possible to identify the location of each patient's mutation, to investigate prognostic effects of particular mutations and to stratify clinical trials according to mutation type or location.

The only subset of KRAS mutations that seems to be predictive of chemotherapy response is mutation in codon 13, but it is difficult to prove statistical significance because so few patients have been identified.

Similarly, only mutations in exons 19 and 21 of EGFR have been found to predict good responses to EGFR inhibitors, and even these patients eventually relapse; second and third generation inhibitors are being developed.

Shepherd ended her talk by considering another tyrosine kinase mutated in this cancer: ALK.

The ALK inhibitor crizotinib was recently approved for treating ALK-mutated NSCLC following a key Phase II trial.

The first cases of resistance to this drug were reported in the same issue of the New England Journal of Medicine as that trial, indicating just how fast we now need to move to develop novel therapies and overcome new resistance mechanisms.