CancerConnect News: Patients with advanced Hodgkin lymphoma (HL) who were treated with a multi-drug regimen that included the precision cancer medicine Adcetris (brentuximab vedotin) had a 23-percent reduction in the risk of disease progression, death, or the need for additional therapy, compared with patients who received the standard treatment for advanced HL.1
Hodgkin’s lymphoma is a cancer of the lymph system. An estimated 8,200 individuals will be diagnosed in the United States in 2017. Standard first-line treatment of HL typically involves chemotherapy, often with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). ABVD cures about three-quarters of patients and has been the standard treatment since the 1970s. One major problem with ABVD is the lung toxicity associated with bleomycin. Researchers are finding that the best way to modify ABVD may be to add or substitute a novel agent such as Adcetris.
Adcetris is a precision cancer medicine that targets a protein known as CD30, which is present on Hodgkin lymphoma cells as well as cells from other cancers. Once Adcetris enters CD30-positive cells, it releases the potent chemotherapy drug monomethyl auristatin E. Adcetris has shown significant clinical activity and a manageable safety profile in patients with relapsed or refractory Hodgkin’s lymphoma.
Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
In order to reduce the risk of HL recurrence and avoid bleomycin lung toxicity researchers previously conducted a small phase I clinical study that evaluated Adcetris as an addition to ABVD or as a substitute for bleomycin 2 The results of this trial suggested that HL outcomes could be improved so a larger comparative trials was initiated to confirm these results.
In the current study, 1,334 patients with previously untreated advanced HL were treated with either the historical standard therapy of ABVD or Adcetris plus doxorubicin, vinblastine, and dacarbazine (A + AVD). When directly compared 82.1% of HL patients treated with A+AVD survived 2 years without cancer recurrence compared to only 77.2% of those treated with ABVD. The experimental combination of AVD did cause more nerve damage, episodes of fever, and neutropenia than ABVD. The doctors reported that the nerve damage largely reversed during follow-up.
A + AVD appears to produce superior outcomes for the initial treatment of advanced HL and may represent a new standard of care. Although HL are often still cured with stem cell transplantation when they relapse following initial therapy, improving the outcomes with initial treatment can spare patients the need to undergo aggressive salvage treatment.
- Joseph M Conners et al: Brentuximab Vedotin Plus Doxorubicin, Vinblastine, Dacarbazine (A+AVD) As Frontline Therapy Demonstrates Superior Modified Progression-Free Survival Versus ABVD in Patients with Previously Untreated Stage III or IV Hodgkin Lymphoma (HL): The Phase 3 Echelon-1 Study