Mark G. Kris, MD
The 7th Annual New York Lung Cancer Symposium offered a comprehensive overview of the latest research into targets and treatment strategies for patients with lung cancer.
During the one-day symposium, more than a dozen oncologists presented information on emerging therapeutic targets for squamous non–small cell lung cancer (NSCLC); the optimal application of tyrosine kinase inhibitors (TKIs) in lung cancer driven by EGFR
mutations or ALK
rearrangements; strategies for patients with poor performance status; approaches to maintenance therapy; and treatments in the pipeline.
In an interview with Oncology & Biotech News
, Mark G. Kris, MD, chief of the Thoracic Oncology Service at the Memorial Sloan-Kettering Cancer Center in New York City and program co-director of the New York Lung Cancer Symposium, offered insights about those and related issues.OBTN: The discovery of therapeutic targets in the squamous form of NSCLC is a critical area, since there are fewer effective therapies for that disease subtype than for adenocarcinoma. What is on the horizon for patients with this disease?
Worldwide, squamous cell carcinoma (SCC) is a very common form of lung cancer, and in the United States it comprises approximately 25% of lung cancers. Since we’ve had many new developments in adenocarcinoma, the focus has been on that illness, whereas in the past it was on small cell lung cancer because of its sensitivity to chemotherapy. One thing we’re learning now is that SCC, too, has characteristics that can be exploited to get better results for patients.
The first example of that is the trial by Giorgio Scagliotti, MD, PhD, that analyzed the effects of different chemotherapies—either pemetrexed or gemcitabine in combination with cisplatin—in patients with advanced NSCLC (J Clin Oncol
. 2008;26:3543- 3451). The pemetrexed combination was more successful in lengthening life in adenocarcinoma, while the gemcitabine combination was better in patients with SCC.
Another example is the paradox of bevacizumab. In bevacizumab’s early clinical testing, while patients with SCCs had severe and immediate shrinkage of their cancers, it led to hemoptysis and often fatal consequences. There was a tremendous sensitivity to bevacizumab that precluded safe use, which is another reason it’s very important that we determine whether a patient has SCC.
We now know that, just like in adenocarcinoma, there are specific drivers for SCC. We’ve found amplification of the FGFR1
gene and mutations in PI3 kinase
, and DDR2
, and we’re now developing clinical trials to find agents that go after and potently inhibit those targets. It’s an emerging area just ripe for benefit and, as the years go on, I think we’re going to see the same kind of benefit for patients with SCC as we have with adenocarcinoma.There has been recent success with the use of TKIs to treat patients whose lung cancer is driven by EGFR mutations or the ALK rearrangement. What’s new in this area?
Any oncologist treating lung cancer has seen the very dramatic benefit that can occur with the use of TKIs like erlotinib or gefitinib in patients whose tumors have EGFR
mutations. With a proper dose, you can pretty much guarantee a response to therapy, manageable side effects, and a level of lifestyle preservation we’ve never had before. Most people continue their jobs and their participation in family life and community and athletic activities.
To find the right patients for these treatments, you need to know that they have the driver, which means you have to do mutation testing. Our guidelines have been changed to recommend testing specifically for EGFR
and the ALK
rearrangement at the time of diagnosis for every patient with adenocarcinoma and selected patients with SCC—those whose diagnosis is less certain because their biopsy specimen was tiny, and never-smokers, whose cancers often have an adenocarcinoma component.
While we can guarantee that the benefit from treatments like erlotinib or crizotinib will last 1 to 2 years, the agents then stop being helpful and cancer starts growing again. We’ve learned that there are three possible scenarios when that happens. First, and blessedly commonly, the cancer grows extremely slowly, by a few millimeters from x-ray to x-ray, and the patients are not harmed. In those cases, I would continue the TKI. The second possibility is that growth occurs in only one spot, and in that situation a good strategy is to obliterate the growth and then go back to the TKI, which can keep the patient alive for years. The third scenario is that the cancer is causing symptoms and growing in multiple spots, and in that case I recommend continuing the TKI and adding in another drug, generally a chemotherapy.