PracticeUpdate: Haematology & Oncology

Dr Roy Herbst on practical aspects of immunotherapy for thoracic cancers AMERICAN SOCIETY OF CLINICAL ONCOLOGY 2016 ANNUAL MEETING 8

Roy S. Herbst MD, Ensign Professor of Medicine and Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven, Connecticut, discusses the impact of immunotherapy on thoracic cancer with PracticeUpdate’s Dr Farzanna Haffizulla.

Dr Haffizulla: During the poster discussion session, Dr Naiyer Rizvi presented data on the use of immuno- therapy for many thoracic malignancies. What’s your opinion on these data? Dr Herbst: Immunotherapy has changed the way we look at thoracic cancer. I lead the thoracic oncology program at the Smilow Cancer Hospital at Yale; I used to lead the program at MDAnderson for many years. I can tell you that – aside from targeted therapy, in which you know there’s a genetic defect, you have a target, you give an EGFR inhibitor, an ALK inhibitor – I’ve never seen anything as impressive as immunotherapy for many of these diseases. Now, the caveat is, as well as it works, it still only works in about 1 in 5 people; but, if you look at immunotherapy in lung cancer, mes- othelioma, patients are coming in who have no genetic drivers, who would have gotten chemotherapy, and had a survival of 6 months to a year, and now we are seeing people live longer. That’s important, I think, for your audience. Everyone else who sees these patients – the pulmonologist, the cardiologist, the internist – now needs to realise that there’s a whole new breed of patients with lung cancer, who are, maybe not cured of their disease, because it’s too soon to say that immunotherapy is curative, but who are living with the cancer. But, as you activate the immune system against a cancer, you do activate it against the thyroid; so you’re going to see a great deal of thyroid issues. Against the colon, you might see colitis. Against the lung, pneumonitis. Something to really keep an eye on, skin rash, other issues. But it really is a huge advance. Dr Haffizulla: ASCO named immunotherapy as the clinical cancer advance of the year for 2016, and you said it perfectly when you mentioned that this is now a whole new arena. Not just for oncologists, for all healthcare providers involved in caring for that par- ticular patient. How do you propose we translate some of that information, and this new thought process, throughout the medical community? To increase the collaborative spirit, as it were, as we’re seeing immu- notherapy on the horizon with such success? Dr Herbst: I lead a SPORE, which stands for Special- ized Programs of Research Excellence. It’s a large grant for lung cancer; we’re one of four sites in the United States that has one, and through the grant we’re actual- ly studying this very carefully. In science, in medicine,

the fact that we’re seeing activity, proof of concept, is huge. Everyone is so excited about it at ASCO, and they should be, because 20% response in a disease that kills 200,000 Americans a year and 1.5 to 2 million people in the world a year is a huge advance; but we still have to figure out why it works in some and not others. One of the things we’re very focused on in our research, and we’re presenting some data here and at other meet- ings this year, is what is it about those patients who respond and then become resistant? So, we’re doing biopsies at our centre at the start of treatment and after the patients become resistant to ask what’s different, and if there is any way that we can then stimulate them to respond again. Or what is it about those patients who never benefit, those primary resistant patients? That’s where combinations of drugs are going to come in, and as I walk through the halls of ASCO, that’s what the posters are about. In fact, I’m presenting one myself on a combination of pembrolizumab and ramucirumab, an angiogenesis inhibitor, and, while the results are early, we’re showing a safe combination and potentially a combination that could be more active than one drug alone, and that now needs to go to further study. Dr Haffizulla: I think that you mentioned something extraordinarily vital, in studying the tumour and then the changes that happen in that particular tumour, not only after treatment, but as it metastasises. You know, understanding the proteins that are translated and expressed in those particular tumours and then using targeted therapy, individualising the treatment and maximising use of the immune system. Dr Herbst: Exactly. One of the biggest papers here at ASCO basically shows that, in profiling tumours and by knowing what’s going on, you are able to treat them better; and that makes sense. If a car comes in to your shop, and it’s not running, you wouldn’t just start throwing stuff at the car; you’d figure out what’s exactly wrong. It’s much more important in a human.

Farzanna Haffizulla MD, FACP, FAMWA, practices general internal medicine in Florida. She was the national president of the American Medical Women’s Association (AMWA) 2014–2015.

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY