Intensified Chemotherapy and Dose-Reduced Involved-Field Radiotherapy in Patients With Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD11 Trial [Hematologic Malignancies]

JCO:

The results of HD11 are published (after having been available online for the last month). HD11 was a counterpart to the HD10 study which looked at early favorable Hodgkin's disease. HD11 was the unfavorable early stage patients, defined as the presence of any of the following: large medistinal mass (greater than 1/3 of the maximum thoracic diameter), extranodal disease, involvement with less than 2 nodal areas, and an elevated ESR (less than 50mm for IA and IIA, and less than 30mm for IB and IIB).
This was a 2x2 trial, looking at escalating chemotherapy (comparing the standard ABVD to BEACOPP), and de-escalating RT (30Gy to 20Gy). Unfortunately, the answer was not clear cut, with both of the comparisons being negative (i.e. BEACOPP was not superior to ABVD, and 20Gy was not "non-inferior" to 30Gy). Of course the temptation is to the look at each of the four arms individually - in which it was observed that the escalation of BEACOPP may conterbalance the descalation of 20Gy, but in the end, one must look on this as a unplanned subgroup analysis.

At the end of the day what are we left with from HD10 and HD11? In favorable patients, a new standard of 20Gy and 2 cycles of ABVD is established, but in unfavorable disease ABVD x4 with 30GY IFRT still stands.

Link and Abstract:

Intensified Chemotherapy and Dose-Reduced Involved-Field Radiotherapy in Patients With Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD11 Trial [Hematologic Malignancies]: "Purpose

Combined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied.

Patients and Methods

Patients age 16 to 75 years with newly diagnosed early unfavorable HL were randomly assigned in a 2 x 2 factorial design to one of the following treatment arms: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy of IFRT; four cycles of ABVD + 20 Gy of IFRT; four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP_baseline) + 30 Gy of IFRT; or four cycles of BEACOPP_baseline + 20 Gy of IFRT.

Results

With a total of 1,395 patients included, the freedom from treatment failure (FFTF) at 5 years was 85.0%, overall survival was 94.5%, and progression-free survival was 86.0%. BEACOPP_baseline was more effective than ABVD when followed by 20 Gy of IFRT (5-year FFTF difference, 5.7%; 95% CI, 0.1% to 11.3%). However, there was no difference between BEACOPP_baseline and ABVD when followed by 30 Gy of IFRT (5-year FFTF difference, 1.6%; 95% CI, –3.6% to 6.9%). Similar results were observed for the radiotherapy question; after four cycles of BEACOPP_baseline, 20 Gy was not inferior to 30 Gy (5-year FFTF difference, –0.8%; 95% CI, –5.8% to 4.2%), whereas inferiority of 20 Gy cannot be excluded after four cycles of ABVD (5-year FFTF difference, –4.7%; 95% CI, –10.3% to 0.8%). Treatment-related toxicity occurred more often in the arms with more intensive therapy.

Conclusion

Moderate dose escalation using BEACOPP_baseline did not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.