SAN DIEGO – In the long run, standard chemotherapy alone is more effective than radiation in keeping patients with limited-stage nonbulky Hodgkin’s lymphoma alive, according to updated results from an intergroup trial in 405 patients.
At 12 years, 94% of patients receiving ABVD – doxorubicin (Adriamycin), bleomycin (Blenoxane), vinblastine (Velbe), and dacarbazine – chemotherapy were alive, compared with 87% receiving subtotal nodal radiation with or without chemotherapy (hazard ratio for death, 0.50; P = .04).
Although 5-year data showed that patients treated with radiation experienced greater disease control, the survival advantage with chemotherapy resulted from a lower rate of death from other causes, Dr. Ralph M. Meyer said at the annual meeting of the American Society of Hematology.
A total of 12 patients in the ABVD arm died: six due to Hodgkin’s, four to a second cancer, and two due to cardiac causes. In contrast, 10 of the 24 deaths in the radiation arm were due to a second cancer. There were two deaths due to cardiac events, four to Hodgkin’s, three fatal infections, and five other deaths.
Dr. Meyer acknowledged that interpretation of the results is bound to be controversial because subtotal nodal radiation is no longer current practice as it is considered excessive. Patients today with low-risk stage IA or IIA nonbulky disease typically receive two cycles of ABVD with 20 Gy of involved-field radiation therapy. Although modern technology has reduced radiation exposure, radiation therapy would still include the coronary artery, heart, and substantial areas of the subdiaphragmatic, he said at a press briefing.
Dr. Ralph Meyer
What is clear from the National Cancer Institute of Canada Clinical Trials Group and Eastern Cooperative Oncology Group study is that measures of disease control, like freedom from progressive disease, are not accurate surrogates for long-term overall survival in patients with stage I-II nonbulky Hodgkin’s lymphoma, said Dr. Meyer, director of the National Cancer Institute of Canada Clinical Trials Group.
"New proxies that predict for risks of late-treatment effects are needed," he said.
Trials are testing the use of PET scanning during therapy to identify patients who may receive chemotherapy alone. It is hypothesized that if PET scans are negative and patients are in remission after two cycles of chemotherapy, the cure rate will be high with further chemotherapy alone, whereas radiation therapy or some other form of chemotherapy should be considered if there is residual PET activity.
How the use of PET will alter current treatment management will be another contentious issue since results from ongoing trials are not expected for 2-3 years. Moreover, the trials are limited because they are using disease control and progression-free survival as end points, which the current trial has shown are not good proxies for overall survival, Dr. Meyer said.
"Thus it will cause issues and interpretation as to how to proceed with these results," he said.
Dr. Meyer and his associates randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin’s lymphoma to receive ABVD chemotherapy alone or subtotal nodal radiation at a dose of 35 Gy in 20 daily fractions. Patients in the radiation group with a favorable risk profile received radiation only, while those with an unfavorable risk received two cycles of ABVD followed by radiation therapy. Median follow-up was 11.3 years.
At 12 years, freedom from disease progression was 92% with radiation vs. 87% with ABVD chemotherapy (HR, 1.91; P = .05,), Dr. Meyer said. Event-free survival was similar at 80% with radiation therapy and 85% with ABVD (HR, 0.88; P = .60).
The results were simultaneously published in the New England Journal of Medicine (N. Engl. J. Med. 2011 [doi:10.1056/NEJMoa1111961]).
Dr. Meyer reported honoraria from Lilly and Celgene.