A recent randomized phase 2 trial has raised significant safety concerns about adding consolidative thoracic radiotherapy to atezolizumab maintenance for patients with extensive-stage small cell lung cancer. The combination produced substantially more serious and fatal adverse events without improving survival.
Atezolizumab plus carboplatin and etoposide, followed by atezolizumab maintenance, became a first-line standard after the phase 3 IMpower133 trial demonstrated longer overall survival than chemotherapy alone. The phase 3 CREST trial found that radiotherapy improved 2-year overall survival and reduced intrathoracic progression among patients who responded to chemotherapy.
These findings supported investigation of whether the strategies could be combined safely. The TREASURE trial enrolled adults with extensive-stage small cell lung cancer who achieved at least stable disease following induction carboplatin-etoposide-atezolizumab. They were randomly assigned to atezolizumab maintenance with or without radiotherapy.
At 20 sites in Germany and Austria, 68 patients were randomly assigned to atezolizumab maintenance with radiotherapy at 30 Gy in 10 fractions or atezolizumab maintenance alone. Although 104 patients were planned, recruitment ended early after the safety monitoring committee identified more fatal adverse events in the radiotherapy arm.
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Median overall survival was numerically shorter with radiotherapy plus atezolizumab than with atezolizumab alone: 6.7 months vs 13.4 months, respectively. Median progression-free survival was similar between groups at 2.4 vs 2.6 months.
The clearest finding was the difference in toxicity. Serious adverse events occurred in 61.3% of evaluable patients receiving the combination compared with 18.2% receiving atezolizumab alone. Fatal adverse events occurred in 19.4% and 3.0%, respectively.
Infections and respiratory disorders predominated; patients receiving radiotherapy experienced more pulmonary and urinary infections, pneumonitis, dysphagia, esophagitis, and fever. A time-to-event analysis associated radiotherapy with increased adverse event risk.
Patients receiving radiotherapy developed pronounced, persistent lymphocyte depletion as adverse events accumulated. By maintenance cycle 2, depleted lymphocyte counts were reported in 91.7% of assessed patients in the combination arm vs 13.6% in the control arm.
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Lower baseline diffusing capacity of the lungs for carbon monoxide was also observed among combination-arm patients with fatal adverse events, although the small sample limits firm conclusions.
The results reinforce the pharmacist’s role in reviewing pulmonary history and function, trending blood counts, and rapidly evaluating fever, cough, dyspnea, dysphagia, or signs of infection. Multidisciplinary teams should carefully weigh overlapping immune- and radiation-related toxicities.
The study found that patients receiving the combination experienced serious adverse events, compared to those receiving atezolizumab alone. Additionally, patients in the combination arm experienced fatal adverse events, compared to those in the control arm.
These findings have significant implications for the treatment of extensive-stage small cell lung cancer, and further research is needed to fully understand the potential risks and benefits of combining radiotherapy with atezolizumab maintenance.
