A new drug trial shows that this combo of drugs can help people with this type of refractory lung cancer live longer, even after other treatments have failed.

The Lung Cancer Master Protocol (Lung-MAP) showed that patients with advanced non-small-cell lung cancer who had developed on previous immunotherapy lived considerably longer when treated with ramucirumab (Cyramza®) plus pembrolizumab (Keytruda®) than when treated with one of the current standard therapies for this type of cancer.

The risk ratio for overall survival (OS) time between patients in the investigational arm and those in the standard-of-care arm was 0.69, with a confidence interval of 80%. (0.51-0.92). The two arms had median OS times of 14.5 and 11.6 months, respectively.

The findings were presented at the American Society of Clinical Oncology’s (ASCO) 2022 annual conference in Chicago (abstract 9004) and published in the Journal of Clinical Oncology.

The study, called S1800A, was part of Lung-MAP, the first lung cancer precision medicine trial.

“This is the first trial,” according to Dr. Karen Reckamp, “to show a survival benefit with ICI and VEGFR inhibition for patients with advanced lung cancer who have experienced tumor progression on prior ICI.”

Pembrolizumab is an immune checkpoint inhibitor (ICI), while ramucirumab is a vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor, a type of medication that inhibits an enzyme involved in the formation of blood vessels.

136 individuals with stage IV or recurrent non-small-cell lung cancer were recruited in the randomized phase 2 S1800A study. These people had been treated with ICIs before. Before the patient entered the S1800A trial, all patients’ malignancies had become resistant to these medications and had grown or spread.

The trial’s primary goal was overall survival. The progression-free survival time (PFS) and objective response rate were used as secondary goals (ORR). The researchers found no significant difference between the arms in PFS (hazard ratio [80% confidence interval]: 0.86 [0.66-1.14]; medians: 4.5 months on the ramucirumab plus pembrolizumab arm and 5.2 months on the standard of care arm) or in ORR (22 percent vs. 28 percent).

Side effects of the treatment of grade 3 or higher were seen in 42% of the patients on the ramucirumab plus pembrolizumab arm and 60% of the patients on the standard of care arm.

In the control arm of the trial, the doctor and patient chose four standard chemotherapy treatments: docetaxel plus ramucirumab, docetaxel alone, gemcitabine, or pemetrexed. Docetaxel plus ramucirumab, the most active medication approved in this scenario, were given to about two-thirds of patients on conventional therapy.

The researchers point out that because S1800A had such a small sample size, the results of the experiment cannot be considered final, and that the combination should be explored in a bigger trial.

“These results represent a potential paradigm-changing regimen in a setting where limited options exist,” said Reckamp. “A phase 3 trial of the combination is warranted to better evaluate the impact.”

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