“Immunotherapy has opened up a new avenue of research”
The treatment of lung cancer has advanced considerably in the last few years. Which of these advances would you deem most important from the clinical point of view?
We think of lung cancer as a generic term, but actually it is a term that encompasses many different diseases. EGFR-mutated lung cancer, squamous lung cancer, and ALK-positive lung cancer are completely different diseases with different biologies and different behaviours. Within each of the main subtypes of lung cancer, huge advances are being made. From my point of view, this year’s most exciting data is the activity of immune checkpoint inhibition in squamous lung cancer that was shown in the CheckMate 017 trial presented at the ASCO Congress. These were landmark results that are practice changing. Within a few weeks of that data being presented, an expanded access programme became available in the UK, and I started to prescribe nivolumab to patients. I have seen some absolutely dramatic responses; the course of disease was completely changed with that PD-1 antibody in some very sick patients. An area with a very high unmet need is also small-cell lung cancer, where immunotherapy shows promise as well. Immunotherapy has opened up a whole new avenue of research in cancer treatment. Many other drugs are being developed, and combinations of these with CTLA-4 antibodies are being tested. Also, investigations are ongoing in the adjuvant setting. Of course, these drugs are expensive. I work in the UK, where access to new drugs is not always straightforward, but my preliminary experience has been very encouraging. New understanding of the side effects is constantly emerging, which is the one concern I have.
One of the other exciting new areas is our understanding of acquired resistance in EGFR-mutated lung cancer. Data with the new third-generation inhibitors rociletinib and AZD9291 are being presented. Overall, there are developments in almost every facet.
Are new treatments being implemented in the real-world setting to a sufficient degree?
I think the problem with new treatments is that there are all sorts of different issues, such as the country you work in. Each country has its own regulatory process, its own funding pathway, and its own way of managing health care. That means there is a wide variation in practice around the world. The main issue that we have in the UK is the cost of the drugs and the fact that it is a socialised health-care system that has a finite set of resources. It is therefore very difficult to fund some of the latest drugs for all cancers. The developments that are going on in lung cancer are also going on in colorectal cancer, in breast cancer and in all the other malignancies. All of these drugs need to be funded. However, the real-world limitation is not just about money. The ability of oncologists to keep up-to-date is being stretched now because of the increasing complexity. It is very difficult for a busy oncologist to even know all of the options that are available. Also, the treatment has to be delivered, which calls for chemotherapy units, trained nurses, support staff and primary care professionals who know what to do once side-effects occur. Overall, it is a huge, complex web that needs to be developed, and this will be a big challenge for the world.
Can you observe improved survival in your patients as a result of new treatments?
I can definitively answer that as a yes. Junior doctors who come to my lung cancer clinic almost always comment within the first week that they cannot believe that all these patients are alive. They are patients with stage-IV lung cancer, who have druggable mutations and who have been alive with a range of treatments for 2 or 3 years, or sometimes even up to 4 or 5 years. We just did not observe that 5 or 10 years ago. Of course we need to appreciate that there is a huge drop-off; many patients die very quickly after diagnosis, so a certain selection bias applies to the survivors, but there can be no doubt that things have improved considerably. Patients with brain metastases, for example, are now able to have resections or stereotactic radiotherapy, and they live for much, much longer periods of time.
Which molecular targets deserve the greatest attention at present?
To my mind, the degree of benefit demonstrated in lung cancer with immunotherapy means that this is the area where we really need to try and improve upon what we already know. There may well be combinations of drugs that will give even greater benefits. However, it is a very complex area. There are a multitude of similar drugs that are being developed by different companies with different biomarkers looking at different subgroups of patients.
Will new findings change the future of lung cancer prevention and early detection?
There is a lot of really interesting emerging data about screening and early detection of lung cancer. We now have irrefutable evidence that screening will identify patients with lung cancers early. If some sort of national and international screening system is established, I am confident that we will be able to detect more cases earlier and give people curative treatment when they are able to receive it.
Which patient characteristics must be taken into account for treatment decisions?
The key aspect about treating patients with cancer is their performance status. The treatment I prescribe is mostly chemotherapy, and patients have to be fit enough for that. Otherwise, things are made worse for them. In addition, the patients’ wishes are important. Some are not that interested in survival. They are often quite elderly and want nature to run its course. Others are willing to go to any lengths for even small benefits. I think that it is part of the physician’s job to assess how far your patients want to go, and to give them the best within their wishes. Someone who does not want treatment should not be treated.
What will happen to chemotherapy in the long run?
Chemotherapy is a very, very effective treatment for lung cancer. It improves survival, helps the patients maintain their quality of life, and reduces tumour-related symptoms. Even if new drugs replace chemotherapy as a first-line treatment, it will still be there as a second-line or third-line treatment. It will always be there.
Interview: Riyaz Shah, PhD, FRCP, Kent Oncology Centre, Maidstone Hospital, Maidstone, UK, springermedizin.at