Strides made in lung cancer research to develop more individualized treatment options

Alex A. Adjei, MD, PhD, FACP, discusses important lung cancer news from the past year.

Alex A. Adjei, MD, PhD, FACP, is senior vice president of clinical research, professor and chair of the department of medicine and The Katherine Anne Gioia Chair in Cancer Medicine at Roswell Park Cancer Institute, Buffalo, N.Y. HemOnc Today recently spoke with him about developments in thoracic oncology in the last year.

The results of the IPASS study were voted a top story of 2009 by the HemOnc Today Editorial Board, how did these results impact the lung cancer field?

The results of the IPASS study have certainly had a significant impact, especially in Asia and Europe. For instance, in Europe, gefitinib (Iressa, AstraZeneca) is approved for only EGFR mutant tumors, no matter which line of therapy. In the United States, gefitinib is not approved. However, there certainly has been an impact in the sense that for EGFR mutant tumors more and more physicians are using erlotinib (Tarceva, OSI), another EGFR tyrosine kinase inhibitor, in the front line, but it certainly has not had the same kind of impact here as it has in Asia and Europe.

What new information have we learned about EGFR mutations since the IPASS results were released in 2009?

There is one big thing that the IPASS study showed. Before IPASS, all physicians were using clinical criteria to decide whether to use an EGFR TKI. We would look at factors such as female patients or never smokers with adenocarcinoma. … The IPASS study showed that the clinical criteria, while useful, are not perfect. Even in Asian population, researchers found EGFR mutations in only 60% of the patients.

IPASS showed that it is important to do mutation testing. You can’t just assume that because someone never smoked that they will have an EGFR mutation and will respond to an EGFR TKI. Mutation testing for EGFR in lung cancer has become more common since these results were released.

Do you think that erlotinib and gefitinib — if it gets approved in the United States — would have revised labels that require testing for EGFR mutations, similar to testing for KRAS mutations for cetuximab?

I think if gefitinib were to be approved in the United States, that would be the way it would be approved. However, erlotinib is already approved in all populations of NSCLC, even though clearly, those with mutations benefit the most. However, if gefitinib were to gain approval in EGFR-mutated patients, it may affect the way physicians use erlotinib.

Results from the BATTLE study were released at the AACR Annual Meeting earlier this year. Do you think all lung cancer patients should have biopsies performed to test for mutations prior to treatment?

That is the direction we are heading, but right now, it is premature.

What the BATTLE study showed is that you can set up a system where you can obtain biopsies and look for mutations before treating patients. The problem is that once we do the biopsy, and you test for a molecular marker, at least at this point in time, we don’t have many validated drugs to use based on those mutations. We haven’t accumulated enough data to really say that “X” drug will work for “Y” mutation.

Right now, in lung cancer, one would be comfortable doing that with an EGFR mutation, and even though phase 3 studies are not yet done, with ALK mutations and crizotinib (Pfizer). Other than that, all the other mutations you might find need more research; they have not yet been proven.

We need a little bit more time to generate data, to be comfortable that for this particular mutation this drug will work. Once we have more evidence that for a PI3 kinase mutation, you can use a PI3 kinase inhibitor and for a CMET mutation you can use a CMET inhibitor, then we will be doing more of this. Right now, it is still too early.

What big news in lung cancer came out of the 2010 ASCO Annual Meeting?

The major news out of this year’s meeting involved crizotinib, the Pfizer drug against EML4-ALK translocations. This study was not completely new — it was first presented at last year’s ASCO — but it was this year’s ASCO Annual Meeting where it generated a lot more robust data. In the study, the researchers found that patients with tumors that have EML4-ALK translocation respond very well with crizotinib. These positive findings are along the lines of what was found with EGFR mutations, building on our knowledge of personalized therapy. That was the biggest news in terms of positive data.

Unfortunately, a lot of the other news, in terms of studies that people have been anticipating, were negative trials.

One was a phase 3 trial with a monoclonal antibody against the IGF-1 receptor — figitumumab — in patients with lung cancer (see page 32). This study was stopped because of a lack of efficacy and toxicity. Another negative study involved a TRAIL-R1 agonist monoclonal antibody — mapatumumab — combined with chemotherapy in lung cancer. These studies certainly give us pause and help us to see that we really need to understand molecular characteristics of these tumors a little bit more and will have to work harder to identify the appropriate patient cohorts for specific treatments.

What research are thoracic oncologists anticipating in the next year?

We continue to look forward to more work being done in looking at molecular subsets of lung cancers and finding drugs that are active in those subsets. We are no longer treating lung cancer as one big disease, but rather we are trying to divide it into different classifications in order to find drugs that work in smaller groups. – by Leah Lawrence