Biomarker-Based Lung Cancer Trials Seek to Fast-Track Therapies

Lung cancer has a low overall survival rate: Just 15 percent of patients live beyond five years. When the disease is diagnosed late, the rate gets significantly worse.

“If you talk about patients with incurable stage IV lung cancer, the average survival is about a year,” says Nathan Pennell, MD, Director of Cleveland Clinic’s lung cancer medical oncology program.

To improve those odds and fast-track appropriate drugs to patients, he and other researchers have embarked on a number of biomarker-driven trials this year.

“We’re beginning to understand that lung cancer is not one common disease anymore — but actually a collection of rare diseases that all happen to start in the lung,” Dr. Pennell says. With that knowledge, biomarker-driven trials represent a move away from “one-size-fits-all” trials, where patients are treated as though they all have the same disease.

Instead, patients most likely to benefit from certain treatments are selected, increasing each trial’s chances of success. Also, because they are so selective, they require fewer patients and take less time to complete. “This leads to faster approval of more effective drugs, and ultimately to better quality and more affordable care for lung cancer patients,” Dr. Pennell says.

Testing drugs to treat rare cancer

Perhaps the most complex and cutting edge of the new trials is the “MAP-Lung” trial, a phase II/III trial designed to analyze tissue from patients with rare subtypes of lung cancer to personalize which drug therapy is most likely to benefit them.

The trial focuses on patients with squamous cell carcinoma of the lung who have had one prior chemotherapy treatment. Tumor biopsies will be used to conduct a comprehensive genomic analysis of the cancer. “Depending on what is found in the individual patient’s cancer, the patient is assigned to one of five different potential treatments,” Dr. Pennell says.

This essentially creates five different clinical trials to test targeted interventions. If the drugs in these trials are successful, they would go directly into a so-called “registration trial,” in which the Food and Drug Administration could approve them to treat lung cancer. This fast-tracking process could cut years off of the typical time required for these drugs to become available, Dr. Pennell says.

The goal is to take the MAP-Lung trial nationwide. “Traditionally, clinical trials have been done either at a single institution like Cleveland Clinic or at a handful of institutions. Now that we’re discovering these rare types of lung cancer, we need to start assembling dozens and perhaps hundreds of institutions to look for and find these rare patients to do clinical trials,” he says.
The trial opened this past summer and has since taken on its first patient.

“Alchemist” trials to improve cure rates

In addition to MAP-Lung, other new studies known as the “Alchemist trials” will focus on improving cure rates for patients with early stage lung cancer.

These trials differ from MAP-Lung in that they use well-understood genetic vulnerabilities in cancer types as opposed to rare cancers, Dr. Pennell explains. “Specifically, we’re looking at EGFR [epidermal growth factor receptor] mutation positive lung cancer, which is about 15 percent of lung cancer, and ALK [anaplastic lymphoma kinase] positive lung cancer, which makes up 5 percent.”

Currently, certain drugs are used to improve the lives and survival of people with incurable cancer who have these genetic markers: erlotinib hydrochloride for EGFR, and crizotinib for ALK.

“We know we can improve the survival of these patients with incurable disease with these markers. Can we then improve the cure rates of curable, early stage lung cancer by adding these drugs after their surgeries?” says Dr. Pennell, explaining the main idea behind the Alchemist trials.

Patients in these trials would have surgery for their stage I, II or III lung cancers. Their tumors would then undergo testing to determine if they are EGFR positive or ALK positive. If they are, patients would be randomly assigned to a drug that targets those specific markers over a two-year period: erlotinib hydrochloride for EGFR, and crizotinib for ALK. Alternatively, they’d be assigned to a placebo for two years.

“In the end, the aim is to determine if more people are cured with the drugs,” Dr. Pennell says.

Photo: © Russell Lee