Lung Cancer: A Road With Many Twists

ADMIRABLE PROGRESS has been made in treating lung cancer in recent years, and more breakthroughs are on the horizon, but the process of making these gains has, admittedly, been a long trip down a winding road.

In most cases, lung cancer crops up as a result of having smoked tobacco products, and over the years public awareness campaigns and even smoking bans have been enacted to end this dangerous habit. It’s a strategy that seems to be working: According to a report released in 2014 by the U.S. Centers for Disease Control and Prevention, 17.8 percent of American adults were smokers in 2013, a drop from the 20.5 percent who smoked in 2005. Also in 2014, the National Cancer Institute reported that lung cancer rates, overall, have continued to drop over the past 20 years, with smoking cessation an important suspected factor. Meanwhile, a protection was added recently for current and former heavy smokers: recommended routine CT screening for early lung cancers. This, too, is expected to help stem the tide of deaths from this disease.

But what about the people who have never smoked tobacco yet still get lung cancer? We’re seeing a rise in these types of cases, and now are figuring out what makes them different, and how they can best be treated. It’s an avenue of discovery that is changing the old perception that lung cancer is both aggressive and fatal.

Improvements in surgery, which has become less invasive with techniques such as video-assisted thoracic surgery and robotic techniques, represent important cobblestones along that path. Also contributing to better treatment, specifically in non-small cell lung cancer (NSCLC), has been the discovery of mutations that drive some lung cancers, and the development of drugs that can target them. For instance, mutations to EGFR or rearrangements in the ALK gene can cause cancer cells to grow out of control. Medications have been developed and approved, in recent years, to target those aberrations and quiet them, slowing down the activity of NSCLC. While metastatic lung cancer remains incurable, these therapies are more effective and less toxic than chemotherapy as initial treatment when these mutations are present.

Unfortunately, there’s a drawback: these drugs work only in the small percentage of patients who have these specific abnormalities, leaving chemotherapy as a mainstay of therapy for the majority of patients. That’s why, right now, the focus is on sorting out who can be helped by novel medications, and how to add more patients to those groups.

Scientists have found that it’s often nonsmokers, Asians and women who have lung cancers that express these mutations, and who thus can be treated with these drugs. While smokers tend to be ineligible for targeted therapies, they can certainly benefit from newly developed and recently approved immunotherapies that stimulate their immune systems to fight the cancer. The revolution in immunotherapy being seen for many cancer types is a welcome addition to the lung cancer field and continues to move forward, with additional immune-modulating agents being tested.

Although small cell lung cancer has different characteristics and no novel therapies have yet been approved to treat it, some targeted drugs and immunotherapies also look promising in clinical trials.

What will we find around the next bend in the road? Further personalization of treatment is being explored in a number of basket and umbrella clinical trials, which treat patients based on the mutations that drive their cancers, rather than the tissue of origin.

Eventually, this could mean that each lung cancer will be treated quite individually based on the messages it sends, making precision medicine the norm in treating this disease.

DEBU TRIPATHY, MD

Editor-in-Chief Professor of Medicine Chair, Department of Breast Medical Oncology The University of Texas MD Anderson Cancer Center

>> Read the Lung Cancer Special Issue here <<