Data from the phase I HD7 through HD11 trials proves promising enough to move on to phase II.
Paul Bröckelmann, MD
Data from the phase I HD7 through HD11 trials proves promising enough to move on to phase II, according to Paul Bröckelmann, MD.
In an interview withTargeted Oncology, Bröckelmann, Department of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, discusses the HD7 through HD11 trials, which examine various forms of radiotherapy in patients with Hodgkin lymphoma, as well as the future of immunotherapy in the disease type.
TARGETED ONCOLOGY:Can you give an overview on your recent presentation?
This year, we presented some updated data on recent, large-scale phase III trials in early-stage Hodgkin lymphoma, looking at first-line treatment. These were the HD7, HD8, HD10, and HD11 trials, and our main goal was to make sure that these therapies are basically safe and effective in the patients.
TARGETED ONCOLOGY:What were the significant findings?
We are talking about 4 trials, so I’ll first summarize the favorable findings in early-stage Hodgkin lymphoma. Basically, we confirmed that the combined modality treatment is superior to single radiotherapy, which was looked at in the HD7 trial. We also confirmed that the HD10 trial is indeed safe, where we established a significant reduction in chemotherapy and radiotherapy density so that two cycles of ABVD followed by radiotherapy is considered a highly effective and optimal treatment for this patient population.
When looking at early-stage unfavorable Hodgkin lymphoma, we first presented the HD8 trial, which established the non-inferiority involved field radiotherapy compared to extended field radiotherapy. This was confirmed with the recent follow-up of 15 years. For the HD11 trial, which is a bit more complicated since it was a 4-arm trial, we basically confirmed that the addition of BEACOPP did not improve the overall outcome, but that it might facilitate a reduction of the radiotherapy dose from 30 grams to 20 grams. This is a reduction that is not possible when following ABVD since the progression-free survival is inferior in these patients.
In terms of overall survival, we did not observe any differences in the HD11 trial.
TARGETED ONCOLOGY:What was the goal looking at all these trials together?
When treating patients with Hodgkin lymphoma, it's always important to get a good balance between efficacy and long-term safety because this involves young patients, and it's of major concern that they don't develop long-term sicknesses from secondary malignancies, organ damage, or relapse of disease. Therefore, we looked at the trials to also accrue data on the extended field radiotherapy patients to look at the rates of secondary malignancies.
In a recent presentation, we were not able to find statistically significant differences between the rates and secondary malignancies between trial arms. When looking at standalone incidences, this ratio was taken from the general German population. We are planning on doing some sub-group analysis in the pool data, which will be presented later this year.
TARGETED ONCOLOGY:In Hodgkin lymphoma, what are some of the biggest challenges you see that need to be tackled?
We are looking at the first-line situation. It's really important to have an effective treatment that is well tolerated in the short- and long-term, and therefore tries to prevent organ damage or secondary neuroplasia. It also tries to prevent infertility, which is of major concern. I think we might move the field forward when we implement targeted agents, such as rituximab vedotin or the anti-PD1 antibodies that were only recently approved in the relapsed setting. This might help to really tailor the treatments that are really tolerable, but effective enough to really cure the patients with one attempt.
The other thing is the guided approach, which involves individualizing the treatment, having a more response-tailored approach, and guiding the intensity of chemotherapy and radiotherapy in the first-line setting. That is being investigated in ongoing clinical trials at the moment.
TARGETED ONCOLOGY:You mentioned immunotherapy approvals. What kind of impact has that had in the relapsed setting, and do you see that coming in earlier?