Lung Cancer
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A new Lung Cancer Master Protocol (Lung-MAP) study conducted within the National Cancer Institute’s National Clinical Trials Network (NCTN) and the NCI Community Oncology Research Program (NCORP) has found that a subset of patients lived significantly longer when they received a combination therapy of ramucirumab (Cyramza) plus pembrolizumab (Keytruda) compared with those treated with current standard therapies.

The patient group—those with advanced non-small cell lung cancer whose cancer had progressed on previous immunotherapy—showed reduced risk of death in patients of 31% compared to standard of care. The results of the researcher were presented last week at the American Society of Clinical Oncology (ASCO) 2022 annual meeting in Chicago and were also published in the Journal of Clinical Oncology.

Pembrolizumab is one of a class of immunotherapy drugs known as immune checkpoint inhibitors (ICIs), and ramucirumab is a vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor, a class of drugs that block an enzyme needed to form blood vessels.

“This is the first trial to show a survival benefit with ICI and VEGFR inhibition for patients with advanced lung cancer who have experienced tumor progression on prior ICI,” said Karen Reckamp, MD, principal investigator and director of the Division of Medical Oncology and associate director of clinical research at Cedars-Sinai Medical Center, Los Angeles.

The randomized Phase 2 study (S1800A) enrolled 136 eligible patients with stage IV or recurrent non-small cell lung cancer. These patients had been previously treated with ICIs. In all cases, patients’ tumors eventually became resistant to these drugs and grew or spread before the patient enrolled in the S1800A trial.

The trial accrued rapidly and with a diverse population, in large part because of the robust outreach of the Lung-MAP master screening protocol. “The unique nature of the public–private partnership of Lung-MAP, supported by the expansive and diverse nature of the NCI’s NCTN and NCORP, allowed us to bring these new therapies to patients with advanced lung cancer nationwide at no cost to patients—an important improvement in patient access,” noted senior author Roy S. Herbst, MD, PhD, deputy director of Yale Cancer Center.

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

The hypothesis of the study was straightforward. Researchers believed that combining a blockade against PD-1 with pembrolizumab and inhibiting VEGFR with ramucirumab might overcome resistance by reducing tumor neovascularization with upregulation of proinflammatory cytokines.

According to Christine Bestvina, MD, of the University of Chicago, the new study findings are significant as, despite the great promise shown in ICI treatments and improved survival, most patients still experience disease progression.

“Previously, this combination had been studied given concurrently with a chemotherapy backbone in IMpower150,” Bestivina said in the ASCO Daily, on June 3. “This combination has demonstrated efficacy in other malignancies including renal cell carcinoma, endometrial cancer, and hepatocellular carcinoma.”

While the Phase 2 study results are encouraging, researchers caution the small sample size isn’t definitive and more research, in a larger trial, is needed.

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

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