TOPLINE

In a phase 2 trial of patients with extensive-stage small cell lung cancer (ES-SCLC), adding consolidative thoracic radiotherapy to atezolizumab maintenance more than tripled the risk for fatal adverse events than immunotherapy alone.

METHODOLOGY

• Chemoimmunotherapy followed by maintenance immunotherapy is standard first-line treatment for ES-SCLC. Whether the addition of consolidative thoracic radiotherapy in the maintenance phase can improve patients’ outcomes has been unclear.
• Researchers conducted an open-label, phase 2 randomized trial at 20 sites in Germany and Austria. A total of 68 patients with ES-SCLC and at least stable disease after induction chemoimmunotherapy (carboplatin-etoposide-atezolizumab) were randomized 1:1 to receive either atezolizumab maintenance plus consolidative thoracic radiotherapy (30 Gy in 10 fractions) or atezolizumab maintenance alone.
• The primary outcome was overall survival, with secondary outcomes of progression-free survival and adverse events.
• Recruitment was prematurely terminated after enrollment of 68 participants due to increased incidence of fatal adverse events in the radiotherapy arm, drastically reducing statistical power from the planned 104 patients.

TAKEAWAY

• Median overall survival in the combination arm was numerically shorter vs atezolizumab only, at 6.7 months and 13.4 months, respectively (hazard ratio [HR], 1.55; P = .34). Median progression-free survival was similar, at 2.4 vs 2.6 months (HR, 0.92; P = .85).
• Serious adverse events occurred more frequently in the combination arm than in the atezolizumab-alone arm (19 patients [61%] vs 6 patients [18%]; P < .001). Overall, six patients (19%) in the combination arm suffered fatal adverse events vs one patient (3%) in the atezolizumab-only arm (P = .04).
• Patients receiving radiotherapy experienced persistent lymphocyte depletion, accompanied by a higher incidence of adverse events, predominantly infections and respiratory disorders.
• In time-to-event analysis, thoracic radiotherapy correlated positively with adverse event risk (HR, 2.47; P = .01), whereas atezolizumab exposure was not (HR, 0.57; P = .06).

IN PRACTICE

“In this randomized clinical trial, combining consolidative [thoracic radiotherapy] with atezolizumab maintenance resulted in an unexpected increase of toxic effects,” the study authors wrote. They added that future studies exploring consolidative thoracic radiotherapy in the maintenance setting “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.”

SOURCE

This study, led by Farastuk Bozorgmehr, MD, of Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany, was published online in JAMA Oncology.

LIMITATIONS

Analyses were exploratory due to premature termination of the trial. The small sample size, particularly in subgroup analyses examining risk factors for fatal adverse events, restricts the generalizability of findings and identification of patient populations who might benefit from or be harmed by combination therapy.

DISCLOSURES

The trial was sponsored by the IKF, Frankfurt Institute of Clinical Cancer Research and funded by Roche. Bozorgmehr received grants from Roche during the conduct of the study and disclosed financial relationships with numerous pharmaceutical companies outside the submitted work. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.