Consolidative thoracic radiotherapy added to standard maintenance immunotherapy increased toxicity without improving survival in first-line extensive-stage small cell lung cancer (SCLC), according to findings from the multicenter phase II TREASURE (AIO-TRK-0320) trial published in JAMA Oncology. Bozorgmehr et al suggested that radiation-induced lymphocyte depletion may have facilitated infections and warrants further investigation as a potential risk factor.
“Cautious patient selection and further investigation to identify those who may benefit without undue risk are required,” the investigators wrote.
Study Details
A total of 68 patients from Germany and Austria with extensive-stage SCLC who had achieved at least stable disease following induction chemoimmunotherapy with carboplatin, etoposide, and atezolizumab were randomly assigned in a 1:1 ratio to receive maintenance atezolizumab with or without consolidative thoracic radiotherapy (30 Gy in 10 fractions).
The primary endpoint was overall survival from randomization. Recruitment was prematurely terminated because of safety concerns.
Increased Toxicity Without Survival Benefit
Median overall survival was numerically shorter with the addition of consolidative thoracic radiotherapy (6.7 vs 13.4 months; hazard ratio [HR] = 1.55; P = .34), whereas median progression-free survival was reported to be similar between the groups (2.4 vs 2.6 months; HR = 0.92; P = .85).
The addition of thoracic radiotherapy was associated with a higher frequency of severe adverse events (19 [61.3%] vs 6 [18.2%] patients; P < .001) and fatal outcomes (6 [19.4%] vs 1 [3.0%] patients; P = .04). Severe adverse events were predominantly infection- and respiratory disorder–related, which the investigators suggested may have been facilitated by lymphocyte depletion following thoracic radiotherapy and lower single-breath diffusing capacity of the lungs for carbon monoxide among patients with fatal adverse events in the thoracic radiotherapy group. Beyond these findings, the investigators identified no additional risk factors because baseline characteristics were well balanced between the treatment arms and between patients who did and did not experience severe adverse events, including fatal severe adverse events.
“In this randomized clinical trial, combining consolidative [thoracic radiotherapy] with atezolizumab maintenance resulted in an unexpected increase of toxic effects, including partially fatal infections and pulmonary disorders, associated with a reduced baseline [diffuse capacity of the lungs for carbon monoxide single breath] and protracted radiation-induced lymphopenia,” the investigators concluded.
They continued, “Thus, in the maintenance setting after chemoimmunotherapy, addition of consolidative [thoracic radiotherapy] cannot currently be recommended outside of clinical trials for unselected patients, and future studies exploring this strategy should consider mitigation strategies, such as dose exposure to highly perfused organs at risk (ie, lungs, heart, and large vessels), radiotherapy timing relative to immunotherapy cycles, and prospectively defined safety stopping rules. Ongoing biomarker analyses may assist in identifying subpopulations with particular risk or therapeutic benefit from this approach.”
Farastuk Bozorgmehr, MD, of Thoraxklinik Heidelberg, Germany, is the corresponding author of the article in JAMA Oncology.
Disclosure: The study was sponsored by the Frankfurt Institute of Clinical Cancer Research and funded by a research grant from Roche. For full disclosures of the study authors, visit jamanetwork.com.
