Around 370 Australians with advanced Hodgkin lymphoma could benefit from subsidised access to a treatment regimen shown to improve progression-free survival while reducing treatment-related toxicity.
Australian patients with advanced Hodgkin lymphoma can now access a new PBS-subsidised first-line treatment regimen that has demonstrated improved progression-free survival and reduced treatment-related morbidity compared with intensive chemotherapy.
From 1 November, brentuximab vedotin (Adcetris, Takeda) was listed on the Pharmaceutical Benefits Scheme as part of the BrECADD regimen for adults with CD30-positive stage IIB Hodgkin lymphoma with a large mediastinal mass and/or extranodal disease, or stage III or IV disease.
The expanded listing is expected to benefit around 370 Australians annually, with patients previously facing costs exceeding $13,400 per prescription without PBS subsidy.
Eligible patients will now pay a maximum of $25 per prescription, or $7.70 for concession cardholders.
BrECADD combines the antibody-drug conjugate brentuximab vedotin with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone.
The PBS expansion follows results from the phase III HD21 trial, which demonstrated superior progression-free survival and significantly lower treatment-related morbidity with BrECADD compared with escalated BEACOPP (eBEACOPP).
The open-label, multicentre trial enrolled 1500 patients aged 18-60 years with newly diagnosed advanced-stage classical Hodgkin lymphoma.
Five-year progression-free survival was 91.5% with BrECADD compared with 89.8% with eBEACOPP, with a reported hazard ratio of 0.619 (98.87% CI 0.369-1.040).
Treatment-related morbidity was significantly lower with BrECADD, affecting 42% of patients compared with 58.7% receiving eBEACOPP (relative risk 0.712; 95% CI 0.643-0.789; p<0.0001).
Professor Mark Hertzberg, professor of haematology at Prince of Wales Hospital and UNSW, said achieving a cure with initial treatment was particularly important for patients with advanced Hodgkin lymphoma.
“Maximising a patient’s likelihood of achieving cure with front-line therapy is a key priority in advanced Hodgkin lymphoma because the chances of successful salvage decline markedly with subsequent lines of treatment,” he said.
Although eBEACOPP has been among the most effective treatments for patients aged 18-60 years, its use has been limited by substantial acute and long-term toxicity.
In HD21, haematological treatment-related morbidity events occurred in 31% of patients receiving BrECADD compared with 52% receiving eBEACOPP.
Sensory peripheral neuropathy of any grade was reported in 39% and 49% of patients, respectively.
However, serious adverse reactions occurred in 39.4% of patients receiving BrECADD compared with 36.4% receiving eBEACOPP.
Related
The most common serious adverse reactions associated with BrECADD included febrile neutropenia, pyrexia, infection, and neutropenia.
The trial also provided encouraging findings regarding fertility preservation, an important consideration given the high proportion of young adults affected by Hodgkin lymphoma.
A secondary analysis published in The Lancet Oncology found substantially higher rates of gonadal function recovery among patients receiving BrECADD.
At four years, gonadal function recovery among women was 95.3% with BrECADD compared with 73.3% with eBEACOPP.
Among men, the corresponding rates were 85.6% and 39.7%, respectively.
The five-year incidence of parenthood among men was also significantly higher with BrECADD, at 9.3% compared with 3.3% (p=0.014).
Among women, parenthood rates were 19.3% and 17.1%, respectively, although the difference was not statistically significant.
Another feature of BrECADD is its PET-guided approach, allowing treatment intensity to be tailored according to early response.
Patients who achieve a negative PET scan after two cycles receive two additional cycles, while those who remain PET-positive undergo four further cycles.
In HD21, approximately two-thirds of patients required only four treatment cycles, corresponding to 12 weeks of treatment.
Professor Hertzberg said the combination of efficacy and reduced toxicity represented an important advance in the treatment of advanced Hodgkin lymphoma.
“Overall, in the HD21 trial, BrECADD has been shown to deliver improved survival outcomes with less acute and lifelong toxicity versus eBEACOPP,” he said.
“With this PBS listing, Australian patients are afforded access to this important front-line treatment regimen.”
Brentuximab vedotin is a CD30-directed antibody-drug conjugate that delivers a cytotoxic agent to CD30-expressing tumour cells.
The drug is also indicated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for previously untreated stage III or IV CD30-positive Hodgkin lymphoma.
David Henderson, country head of Oceania at Takeda, said the listing would broaden treatment choices for eligible Australian patients.
“This PBS listing represents an additional ADCETRIS-based front-line treatment option for eligible Australians with newly diagnosed CD30+ advanced Hodgkin lymphoma,” he said.
“For Takeda, this is about ensuring advances in treatment translate into greater access for Australian patients.”
The expanded listing forms part of a broader package of PBS changes announced by federal Health Minister Mark Butler, including new or expanded access to medicines for cystic fibrosis, thyroid eye disease, and familial hypercholesterolaemia.
The BrECADD listing is authority required, with prescribing subject to PBS eligibility criteria.
