Challenges in Treating Lung Adenocarcinoma

Mohammad Jahanzeb, M.D. discussed the challenges in treating non-driver lung adenocarcinoma. 
BY GINA COLUMBUS @ginacolumbusonc
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).

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.

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

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 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.

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

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.

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