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Though the study did not meet its endpoint, the strategy behind it remains under investigation.
A new study finds that a potential new treatment strategy for certain patients with non-small cell lung cancer (NSCLC) does not increase survival, but the study’s co-author says the research may help pave the way for other new strategies.
The report concerns the use of hypofractionated image-guided radiotherapy in patients with stage II/III NSCLC who are unfit for concurrent chemotherapy due to comorbidities or performance status.
Puneeth Iyengar, MD, PhD, of the University of Texas Southwestern Medical Center, told Managed Healthcare Executive the preferred treatment for patients with this type of lung cancer is chemotherapy and radiotherapy followed up with immunotherapy.
“The problem is, there are quite a few of our lung cancer patients who, because of their lung function, because of other medical morbidities, they cannot tolerate doing chemotherapy and radiation at the same time,” he said.
Since these patients could not tolerate chemotherapy, Iyengar and colleagues wanted to know whether escalating the dosage of radiation for these patients might yield better results than conventionally fractionated radiotherapy. Their idea was to give concurrent chemoradiotherapy-ineligible patients radiation doses of 60 Gy in 15 fractions instead of the conventional 60 Gy in 30 fractions.
“And the idea was that if we could somehow increase the dose per treatment, we could make up—in terms of controlling the local disease—for the fact that there was no chemotherapy on board,” he said.
The investigators had already completed a phase I study showing the escalated dosage was tolerable. The new study, published in JAMA Oncology, was a nonblinded phase 3 randomized clinical trial designed to find out if the therapy would boost one-year overall survival.
The investigators enrolled 103 patients, 96 of whom were able to be analyzed. All of the patients had phase II/III NSCLC, Zubrod performance statuses of at least 2, and greater than 10% weight loss in the previous 6 months, or they were otherwise ruled ineligible for concurrent chemoradiotherapy by oncologists.
Fifty patients were given hypofractionated radiotherapy and 46 were treated with conventionally fractionated radiotherapy. Patients were enrolled between between 2012 and 2018 and were followed for a median of 8.7 months.
Despite the positive phase I study results, Iyengar said a planned interim analysis of the new phase III study made clear that the strategy was not going to reach the primary endpoint of prolonging survival. There was no statistically significant difference in one-year survival between the two groups. Those receiving hypofractionated radiotherapy had a one-year survival rate of 37.7% (95% CI, 24.2%-51.0%) versus 44.6%(95% CI, 29.9%-58.3%) in the conventionally fractionated group. Similarly, the new strategy showed no benefit in median overall survival or progression-free survival.
Though the study did not meet its primary endpoint, Iyengar said the trial generated meaningful data that could someday be used to improve patient outcomes.
“I would argue this is a good foundation to build off of and this could be the tip of the iceberg,” he said.
Iyengar noted that there were some signs in the study that the therapy was doing a good job of controlling disease, even if that did not translate to better survival.
“So it may have been doing its job with respect to controlling the disease, but not with respect to survival because of the toxicity relevant to that patient population,” he said.
Thus, Iyengar added, the research may help inform different strategies and different combinations of treatments for particular populations, including potentially a combination with immunotherapy. He said other research is already underway using different “formulas” of treatment, but all probing the same underlying questions about when and whether hypofractionation might improve outcomes.
Iyengar said despite failing to meet its endpoint, the study could be a long-term success, because it generated data that could help optimize treatment in the future.
“I sometimes feel that we don't take away enough from the studies that don't work the way that we anticipated they would work,” he said. “I think there's a lot of information that can be garnered from those types of studies.”