Late-Breaking Research From Cedars-Sinai Cancer Finds an Immunotherapy Drug Combination Improves Survival for Patients With Immunotherapy-Resistant, Non-Small Cell Lung Cancer

Results of a Phase II clinical trial led by Cedars-Sinai Cancer investigators indicate that an immunotherapy drug combination could extend the lives of those diagnosed with advanced non-small cell lung cancer, one of the most common forms of lung cancer. The research was presented today during the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, with simultaneous publication in the peer-reviewed Journal of Clinical Oncology.

Currently, people diagnosed with advanced non-small cell lung cancer have limited treatment options. Therapies for the disease have improved over the past five years—including advances in immunotherapy—although even after initial tumor response, resistance develops in most tumors.

“This clinical trial shows promise in extending the lives of patients who have lung cancer that has become resistant to immunotherapy treatments,” said Karen L. Reckamp, MD, director of Medical Oncology at Cedars-Sinai Cancer, associate director of Clinical Research at Cedars-Sinai and lead author of the ASCO abstract and simultaneous publication. “This is a game changer for the field, and more importantly, for the patients who may benefit from the treatment.”

The study, known as S1800A, was part of Lung-MAP, a lung cancer precision medicine trial supported by the National Cancer Institute, part of the National Institutes of Health.

The randomized Phase II trial enrolled patients with recurrent non-small cell lung cancer. All enrollees had previously been treated with immune checkpoint inhibitors, a type of immunotherapy designed to help the immune system battle cancer.

In the clinical trial, half of the patients received standard of care, either chemotherapy alone, or chemotherapy plus ramucirumab—an anti-angiogenesis drug that blocks the action of an enzyme needed for the formation of blood vessels, weakening the tumor by depriving it of nutrients. The other half received an immunotherapy combination of an immune checkpoint inhibitor plus ramucirumab.

Patients receiving the immunotherapy drug combination had a median overall survival of 14.5 months, compared with 11.6 months for patients receiving standard of care therapy.

Reckamp notes that two-thirds of patients in the standard of care group chose to receive a combination of chemotherapy and ramucirumab rather than chemotherapy alone, which represents the best standard of care treatment.

Investigators also tracked the length of time before patients’ tumors progressed, called progression-free survival time, and their overall response to therapy. They found no significant difference between patients receiving standard of care versus combination therapy, but Reckamp said there were bright spots even in this data.

“There were patients receiving the combination therapy who had a longer duration of response than those on standard of care,” Reckamp said. “We have seen this pattern in prior immunotherapy trials where overall survival measures the benefit better than progression-free survival or response rate.”

This newly studied combination therapy meant many patients were spared chemotherapy and its associated side effects. Just over 40% of patients in the combination therapy group experienced significant treatment-related side effects, versus 60% of those in the standard of care group.

“These findings offer a potential solution that could change the standard of care for these patients and provide better outcomes for all patients in the future,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer. “Clinical advances like this accelerate progress and move the needle forward for the broader field of cancer research.”

This is the first trial in the second-line setting without a chemotherapy backbone to demonstrate a potential survival benefit compared to standard of care regimens, including docetaxel and ramucirumab, using the Lung-MAP platform.

Reckamp said the results merit further investigation and that a Phase III trial is planned.

The trial was funded by National Institutes of Health/National Cancer Institute grant numbers U10CA180888, U10CA180819, U10CA180821, UG1CA233323, UG1CA189830, UG1CA189971, UG1CA189858 and UG1CA233340; Foundation for the National Institutes of Health; and Eli Lilly and Company and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Read more on the Cedars-Sinai Blog: Immunotherapy—The Fourth Pillar of Cancer Care