When Is the Best Time to Give Patients With Lung Cancer Immunotherapy Everyday Health MenuNewslettersSearch Lung Cancer New Research Raises the Question When Is the Best Time to Give Patients With Lung Cancer Immunotherapy Emerging data suggests that giving some patients with lung cancer immunotherapy before surgery may help train the immune system to fight off later recurrences. By Darcy LewisMedically Reviewed by Thomas Urban Marron, MD, PhDReviewed: May 4, 2021Medically ReviewedAs experience with immunotherapy drugs grows, experts are getting a better sense of how best — and when — to use them. ShutterstockFor years, the standard treatment for early stage non-small-cell lung cancer that hasn’t spread beyond the lungs has been chemotherapy given either before or after surgery to kill off any microscopic remaining tumor that may have spread before the surgery. The results, however, were less than ideal. “Even when surgery goes well, the cancer returns in more than half the patients, and many then die from their disease,” says Nicolas Girard, MD, head of medical oncology at the Curie Institute in Paris, France. But new data from an ongoing study, known as Checkmate-816, presented last week at the virtual annual meeting of the American Association for Cancer Research (AACR) may herald a new paradigm in treatment for these patients. The data showed that adding the immunotherapy drug Opdivo (nivolumab) to standard presurgery chemotherapy in early-stage non-small-cell lung cancer significantly improved patients’ rates of pathologic complete response (pCR) (no evidence of visible cancer in samples removed during surgery). In the study, 24 percent of patients treated with immunotherapy plus chemotherapy prior to surgery achieved this complete response, compared with only 2 percent of patients who received chemotherapy alone. “Once you have the complete disappearance of tumor cells, we expect the risk of recurrence and death will be reduced,” says Dr. Girard, who was lead author of the study. “This is what happened with nearly one-quarter of Checkmate-816 patients.” Girard called the results “highly significant” due to how aggressive non-small-cell lung cancer is, even when diagnosed at an early stage. Checkmate-816 is a phase 3 trial, meaning it’s at the last stage of testing before submitting the data for U.S. Food and Drug Administration (FDA) approval. RELATED: Can You Survive Lung Cancer? Results Were Promising — and Consistent in a Variety of Patients The study included 358 adults with early stage (1b to 3a) non-small-cell lung cancer whose tumors could be surgically removed. Before surgery, 179 patients were randomly assigned to receive standard chemotherapy plus Opdivo. An additional 179 patients received standard chemotherapy alone prior to surgery. Not only did the investigators find that patients who received Opdivo plus chemotherapy had a pCR rate of 24 percent compared with 2.2 percent with chemotherapy alone, the improvement occurred consistently across all patient subgroups. These subgroups included disease stage, lung cancer subtype, PD-L1 status (a marker used to gauge a tumor’s sensitivity to immunotherapy), and how many mutations a tumor carried. Both men and women also had similar responses to the therapy. Another important finding: Adding immunotherapy did not increase side effects or lead to delays in surgery. In the immunotherapy group, 83 percent of patients were able to receive surgery as expected, compared with 75 percent of patients in the chemotherapy-alone group. RELATED: Why Are ‘Never-Smokers’ Getting Lung Cancer? Immunotherapy in Lung Cancer When Is the Best Time to Give It The idea behind Checkmate-816 is that giving immunotherapy as the first treatment after diagnosis — before surgery — rather than reserving it for once the cancer has returned and spread, is that the drug “trains” the immune system to fight back against the disease. “We want to expose patients to immunotherapy as early as possible because their immune system is still effective and the tumor hasn’t yet developed resistance,” Girard says. “If you give immunotherapy after surgery, when the tumor is gone, you stimulate the immune system, but only a small fraction of those immune cells have interacted directly with cancer cells, so it may be less effective.” Additionally, using immunotherapy right after diagnosis may give the earliest opportunity to treat cancer cells that have spread in the body without detection. These stray cancer cells, known as micrometastases, are believed to be the reason why so many lung cancer patients have disease recurrence following surgery. RELATED: 5 Early Signs of Lung Cancer Better Survival in Lung Cancer Calls for New Strategies Checkmate-816 and several other clinical trials are part of a larger trend to explore using immunotherapy earlier in treatment in lung cancer and other tumor types. “Clinical trials comparing both neoadjuvant and adjuvant immunotherapy are ongoing,” Girard says. “Soon we will be able to compare the data to determine the relative effectiveness of each approach.” Girard says this information is crucial because, while lung cancer remains the leading cause of cancer deaths, survival rates are improving. And that has long-term implications for patient care. The relative proportion of patients with late- versus early-stage lung cancer is changing. “It used to be that 60 percent of lung cancer patients had metastatic disease at diagnosis,” Girard says. “But in countries where lung cancer screening is common, only about 30 percent of patients have metastatic disease at diagnosis.” Conversely, the percentage of patients who are diagnosed when the cancer is still in its earlier stages, when it is considered most curable, has increased to 40 percent from 20 percent, Girard says, making it “even more important that we treat patients effectively as soon as they’re diagnosed.” That’s why interest will be high when the patient survival data from Checkmate-816 are released in the years ahead. “The data presented at AACR are just the beginning of the story,” Girard says. “With long-term follow-up of these patients, we will be able to understand what happens when disease recurs and determine if neoadjuvant immunotherapy extends survival or not.” RELATED: New Hope for Previously ‘Undruggable’ Non-Small-Cell Lung Cancer NEWSLETTERS Sign up for our Cancer Care Newsletter SubscribeBy subscribing you agree to the Terms of Use and Privacy Policy. 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