Treating an aggressive type of lung cancer with a combination of immunotherapy and chemotherapy significantly improves patients’ survival compared with chemotherapy alone, according to a study presented yesterday (April 16) at the annual meeting of the American Association of Cancer Research (AACR). The results were also published yesterday in the New England Journal of Medicine.
“Using this combination therapy to treat patients with such an aggressive disease could be an important advance in keeping patients alive and well for longer,” says coauthor Leena Ghandi, a thoracic oncologist at NYU Langone Health, during a press conference at AACR. In an AACR statement that accompanied the press conference, Ghandi calls the results “practice-changing.”
Ghandi and her colleagues studied 616 patients with untreated metastatic non-squamous non-small cell lung cancer (NS-NSCLC) in a Phase 3 clinical trial called KEYNOTE-189: 410 patients were treated with a combination of chemotherapy and the immune checkpoint inhibitor pembrolizumab, while 206 patients received chemotherapy and a placebo. Patients in the placebo group whose disease progressed were allowed to switch into the immunotherapy group.
After 10.5 months, 69 percent of patients treated with the immunotherapy and chemotherapy combo were still alive, compared to 49 percent of patients who received chemotherapy with the placebo. In patients who received the combination treatment, 48 percent saw their tumors shrink considerably, compared with 19 percent who only received chemotherapy. On average, patients who received the combination therapy lived twice as long as patients who were not treated with it.
Drugs that inhibit the cell surface receptors PD-1 and PD-L1 have been previously found to be effective therapies for targeting NS-NSCLC tumors that lack mutations in the genes EGFR and ALK. Pembrolizumab has already replaced chemotherapy as the treatment of choice in patients with tumors that express PD-L1 in more than 50 percent of cells, according to the AACR statement. However, the KEYNOTE-189 trial did not assess whether patients with high PD-L1 expression benefited from the combination therapy.
“I think most of us in the field would be quite hesitant to give up on PD-L1, or some [other] biomarker, because clearly not all patients are benefiting” from the combination therapy, Gandhi says. “We do need to focus more on how to differentiate the patients who will get the most benefit.”