Interview: Modern agents enable dramatic responses even in phase I trials
Herbert Ho Fung Loong, MD, Clinical Assistant Professor, Department of Clinical Oncology, Deputy Medical Director, Phase 1 Clinical Trials Centre, The Chinese University of Hong Kong, China
Looking at phase I clinical trials that are ongoing at the moment, which novel approaches in advanced lung cancer do you deem most promising?
At present, a lot of developments for many types of cancer are being tested in phase I trials, not only for lung cancer. I think that in the past we were very agnostic about whether or not the mechanism of a phase I drug will work for a particular cancer. Today, however, with many drugs being targeted therapies, we have a pretty good idea already in the preclinical setting about which specific targets may be useful. Particularly in lung cancer, a lot of the new molecularly targeted agents have shown promise; this applies for example to the very small subgroup of tumours with RET alterations. Results in this area were announced at this meeting including the phase I trial on the RET inhibitor LOXO-292 that was further updated by Geoffrey Oxnard and showed very dramatic responses . Two or three years ago, we did not see such dramatic responses in a phase I clinical trial.
What are the peculiarities of lung cancer research compared to other areas of cancer research?
The peculiarities of lung cancer research are severalfold. One is the patient population. Lung cancer is a very big cancer in terms of patient numbers, and there is a large variety of tumours within lung cancer itself. While some are molecularly driven and the treatment approaches would be addressing these targets, we do not know the molecular targets for others, and immunotherapy is a very big avenue here. It is the balance between the two; balancing which patients should go into trials, identifying the molecular drivers and looking at them. On the other hand, what is the role of immunotherapy even in patients with molecular drivers? The greatest challenge is how to combine these two. I think these are issues we do not have good answers for yet.
Which areas within lung cancer research would require more attention, given that this disease needs to be tackled at the level of both prevention and treatment?
With regard to prevention, a very good abstract on screening has been presented at the WCLC 2018 . Certainly there is a proportion of lung cancers for which prevention itself is the best way of treatment in the sense of preventing tumours completely by removing the risk factor, as for small-cell lung cancer. This requires a lot of work, however.
On the other hand, I think that one of the biggest challenges in terms of drug development for lung cancer is the necessity to obtain considerable amounts of tumour tissue as a biomaterial for further analysis. Many times, the initial biopsy is very small. Another issue is the combination of different types of treatment, molecularly targeted therapies as well as immunotherapies, but also the combinations of other modalities of cancer treatment like radiation, surgery and so on. It is a growing field with a lot to learn, but I think we are moving in the right direction.
- Oxnard GR et al., Clinical activity of LOXO-292, a highly selective RET inhibitor, in patients with RET fusion+ non-small cell lung cancer. WCLC 2018, OA12.07
- De Koning HJ et al., Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial. WCLC 2018, PL02.05