Kris Provides Insight Into New Drugs for Lung Cancer

Mark G. Kris, MD

The FDA awarded new approvals or expanded indications for almost twenty cancer drugs in 2013. To gain further insight, we interviewed Mark G. Kris, MD, the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York City, on new drugs and emerging trends specifically in lung cancer.

Two lung cancer drugs won new approvals/indications from the FDA this year—afatinib (Gilotrif) and erlotinib (Tarceva)—but Kris sees far more potential in experimental compounds and genetic tests that help clinicians choose treatments.

“Erlotinib has been the standard of care for initial treatment EGFR-mutant lung cancers for years now, so the expanded indication from the FDA should not change how physicians use it,” said Kris, who added that afatinib, while a different molecule, greatly resembles erlotinib in activity but with more skin and nail toxicities.

“The really interesting drugs for lung cancer, the ones that may bring significant new benefits to patients, are still in trials.”

Among those interesting drugs is a quartet of antibody medications that target the inhibitory T-cell co-receptor PD-1 and the ligand PD-L1: MK-3475, BMS-936558, MEDI4736, and MPDL3280A.

All four molecules uncloak T cells and differ from any existing drug. All of them have excelled in early trials— which Kris believes indicates both the high value of the target and the high probability that at least one treatment will eventually reach the market.

The benefits of all four medications have proven long lasting in many patients and, Kris noted, early combination trials suggest their benefits are additive to those of other immune modifiers targeting CTLA-4.

Another group of exciting experimental drugs that interest Kris are next-generation EGFR tyrosine kinase inhibitors, such as CO-1686 and AZ9291.

Early trials indicate that both of these drugs effectively target not only single mutations but also those that have second-site mutations such as T790M and have thus grown resistant to the first-generation treatments erlotinib and gefitinib. A phase I trial of CO-1686 found tumor shrinkage in about three-quarters of patients with the T790M mutation.

Those same early trials have indicated that the next-generation drugs are far better tolerated than existing medications. Side effects rarely go beyond rash and diarrhea.

Another well-tolerated compound, the monoclonal antibody necitumumab, also received special mention from Kris. Eli Lilly has already announced that necitumumab combined with gemcitabine and cisplatin improved overall survival when compared with chemotherapy alone for patients with advanced squamous lung cancers in a phase III trial.

“This is a badly underserved group of patients,” Kris said. “An effective treatment for them would be an important development.”

Of course, targeted treatments only work when the right patients receive them, which is why Kris believes that the steady improvement in the breadth, accuracy, and affordability of molecular testing services may be the most important advance of all for oncologists this year.

“Just a few years ago, major research hospitals were the only places that could routinely perform genetic tests,” Kris said. “Now, everyone has access to reasonably priced tests that screen for 200 to 300 relevant mutations—tests that radically improve the ability of doctors to prescribe the right treatments. The technology will only get better and cheaper.”