Thoracic RT Yields Improved Survival in Extensive-Stage SCLC

Small-cell lung carcinoma, chromogranin immunostain; source: CFCF, Wikimedia Commons

Though a primary study endpoint was not technically met, thoracic radiotherapy along with prophylactic cranial irradiation (PCI) significantly prolonged overall and progression-free survival compared with PCI alone in patients with extensive-stage small-cell lung cancer (ES-SCLC), according to results of a new study presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Ben Slotman, MD, PhD, of VU University Medical Center in Amsterdam, presented the study and said that previous work had shown that PCI could improve both symptomatic brain metastases and overall survival at 1 year. “In that study, we also noticed that the vast majority of patients after chemotherapy had intrathoracic disease” and intrathoracic progression, he said, which was the impetus for the new study using thoracic radiotherapy.

The trial accrued 498 patients from 42 centers, mostly in the Netherlands and the United Kingdom, though also from Belgium and Norway. All patients had received platinum-based chemotherapy and achieved any response, and were then randomized to either thoracic radiotherapy delivered as 30 Gy in 10 fractions along with PCI or to PCI alone. Patients had no prior radiotherapy to the brain or thorax.

The intention-to-treat analysis had 247 patients in the experimental arm and 248 in the control arm; 9 didn’t receive the radiotherapy mainly because of disease progression between randomization and start of therapy. After a median follow-up of 2 years, 73 of the patients remained alive.

The primary endpoint of overall survival at 1 year was not reached, with a hazard ratio of 0.84 (95% CI, 0.69-1.01; P = .066). That trend reached significance at 18 months, however, and was highly statistically significant by 24 months; 2-year survival was 13% in the experimental arm and 3% in the control group (P = .004). Progression-free survival was also better with radiotherapy, with an HR of 0.73 (95% CI, 0.61-0.87; P = .001). Slotman noted that the progression-free survival difference was not just at the median, but it was maintained with longer follow-up as well.

Finally, intrathoracic progression was seen in 79.8% of the control group and in 43.7% of the radiotherapy group (P < .001).

“Thoracic radiotherapy should be offered in addition to PCI to all ES-SCLC patients who respond to initial chemotherapy,” Slotman concluded.

Walter J. Curran, Jr, MD, of Emory University in Atlanta, was the discussant for the session. He said during a question and answer session that the failure to meet the primary endpoint of overall survival at 1 year should limit that recommendation for this therapy.

“If you’re looking at introducing a new therapy in the management of ES-SCLC, we better kick the tires of this pretty significantly,” he said. “What would be great would be to have a follow-up study where there is significant looks at quality of life specific for lung cancer patients, and does this reduction in thoracic disease result in a meaningfully better life over the life of these patients.”