Treating Lung Cancer With Precision

In lung cancer, prognoses are most dire when disease has reached stage 4, leaving patients, their doctors and the research community eager for improved treatment strategies. With recent advances in the molecular sequencing of non-small cell lung cancer has come a reason for hope — albeit for a small segment of affected patients.

A greater understanding of the genomics of nonsmall lung cancer — in particular, the identification of some genetic mutations that help drive the disease — has led to new medications that target these mutations. A glitch that causes tumors to overexpress or make a mutated version of the epidermal growth factor receptor, or EGFR, resulting in the rapid growth of cancer cells, can be treated with medications that disable that glitch, such as Tarceva (erlotinib) and Iressa (gefitinib). Antibodies to EGFR, including the recently approved Portrazza (necitumumab), can also be effective.

A different gene, ALK, can undergo several rearrangements that drive non-small cell lung cancer, but these mutations can now be targeted with the drugs Xalkori (crizotinib) or Zykadia (ceritinib). There’s even a molecular diagnostic test that can help identify some of the patients most likely to benefit from these drugs.

Unfortunately, these new medications work only for a minority of patients with non-small cell lung cancer, because not much more than 10 percent of them have the targeted mutations. Also, over time, resistance develops — we don’t know exactly how, but much effort is going into deciphering this process. Luckily, there are also other new tactics. Oncologists and scientists alike are excited about immunotherapies for the treatment of non-small cell lung cancer.

Particularly good news is that two recently approved immunotherapies, Opdivo (nivolumab) and Keytruda (pembrolizumab), may help a broader swath of patients than targeted drugs can. In general, immunotherapies tend to work best in smokers or former smokers, whose lung cancers seem to carry more mutations — and who comprise the majority of the population with non-small cell lung cancer. These drugs also may be less likely than targeted therapies to stimulate resistance from cancer. In a small group of patients, at least, immunotherapies seem to spark long-lasting responses. More work is needed to identify more precisely who is most likely to benefit.

While these new types of drugs can’t yet help everyone with advanced lung cancer, researchers are poised to build on their successes as they seek new molecular targets. At the same time, they’re testing additional immunotherapies, and combinations of those drugs, in the clinic.

These precision medicines represent an area of great promise that could vastly change the outlook for patients with this intransigent disease. In the pages of this issue, we share not only the strategies that are available now, but news about what’s waiting on the horizon.

Debu Tripathy, MDEditor-in-ChiefProfessor of MedicineChair, Department of Breast Medical OncologyThe University of Texas MD Anderson Cancer Center