Challenges in Treating Lung Adenocarcinoma

Routine molecular testing for patients with non-small cell lung cancer (NSCLC) will often pick up on common mutations — such as EGFR or ALK — and the patient can receive a targeted agent for that driver. However, patients with non-driver-mutated lung adenocarcinoma have far fewer options, explained Mohammad Jahanzeb, M.D.

“In other words, it’s the ‘non-fun’ stuff,” said Jahanzeb. “It does not include any new mutations, immunotherapy, anti-VEGF antibodies, or any other antibodies. Basically, this is the platinum-based doublet therapy that we have had for more than three decades.”

There are still multiple areas in which chemotherapy can be used in these patients, he adds, including in the first- and second-line settings and as maintenance therapy. Moreover, researchers are comparing cisplatin- versus carboplatin-based regimens, and exploring new options for maintenance treatment.

For example, an ongoing, double-blind, randomized trial is investigating the differences in efficacy and safety between Tarceva (erlotinib) and pemetrexed as maintenance therapy in patients with lung adenocarcinoma (NCT02399566).

A second study is exploring Avastin (bevacizumab) as a maintenance treatment for patients with lung adenocarcinoma who previously received four to six cycles of induction platinum-based doublet therapy plus bevacizumab (NCT02093000).

What treatment changes do you see occuring in this area over the next decade?

In an interview, Jahanzeb, who is professor of Clinical Medicine, Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, discussed why researchers must work on identifying targetable mutations in these non-driver adenocarcinomas and shared his insight on other trends and challenges in the field.It is very exciting—World War II is where, by accident, we saw nitrogen mustard as chemotherapy. Sixty-five years later, by 2010, we still only had less than 10 FDA-approved drugs for lung cancer. In the last five years, we have had more than 10 drugs approved for the disease. Today, there are 600 to 700 drugs in the pipeline.

What combination regimens are currently being studied that could be practice changing?

Aside from this population having limited treatment options, what other obstacles are there?

What we will see now is more and more targeted therapies, many lines of therapy, combinations of immunotherapy agents with targeted therapies, and combinations of checkpoint inhibitors with each other. We will be shrinking the diminishing role of cytotoxic chemotherapy, so it’s a very exciting time.I am very excited about the checkpoint inhibitor combinations, such as Yervoy (ipilimumab) and Opdivo (nivolumab). There are many examples of multiple checkpoint inhibitor clinical trials. I am also very interested in targeted therapy combination trials to inhibit multiple points in the pathway, as well as inhibit multiple pathways that can cooperate with each other. Those are very exciting explorations that are going on right now. One of the major challenges is that there are too many trials that are competing with each other. Also, there is still not enough tissue testing.

You mentioned there being too many ongoing clinical trials. How can the oncology community overcome this?

And, community radiation oncologists, medical oncologists, interventional radiologists and pathologists need to all be sitting in one room—rather than be making these decisions in isolation. Universities and institutions may have tumor boards, but there needs to be a tumor board available for every practice. We are at that point now.I don’t think it will be overcome by any one factor. This is because everybody has their own compound and their own vested interest. They are not interested in helping someone else’s compound. Consortiums of physicians, cooperative groups — even the National Cancer Institute — can align incentives in a way so that the trials are prioritized. Then, somehow there could be centralized clearing mechanisms in which it automatically happens that the best study and the best design survives—and poor studies and poor designs do not survive.