Approvals for ADCETRIS in Frontline Hodgkin Lymphoma (HL): In May 2019, ADCETRIS in combination with AVD (Adriamycin[R], vinblastine and dacarbazine
) was approved by Health Canada for patients with previously untreated stage IV HL.
- The European Commission extended the current marketing authorization of Adcetris (brentuximab vedotin) to include treatment of adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine and dacarbazine
), Takeda Pharmaceutical company Ltd.
TMZ is a prodrug and an imidazotetrazine derivative of the dacarbazine
, 5-(3-dimethyltriazen-1-yl)-imidazo-4-carboxamide (DTIC).
At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine
, reported lead author Paolo A.
This is the sixth FDA-approved indication for ADCETRIS, which also has approval for adult patients with: previously untreated Stage III or IV classical Hodgkin lymphoma, in combination with doxorubicin, vinblastine, and dacarbazine
, HL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation consolidation, cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, sALCL after failure of at least one prior multi-agent chemotherapy regimen, and primary cutaneous anaplastic large cell lymphoma or CD30-expressing mycosis fungoides who have received prior systemic therapy.
This US FDA approval for adult patients with previously untreated stage III or IV cHL was based on the company's clinical trial with of 1,334 patients, comparing Adcetris plus chemotherapy (Adriamycin [doxorubicin], vinblastine and dacarbazine
, or AVD) to a chemotherapy-only regimen common for cHL treatment (AVD plus bleomycin, also known as ABVD).
After receiving an average of six 28-day cycles of treatment, patients treated with Adcetris plus Adriamycin (doxorubicin), vinblastine, and dacarbazine
(AVD) were 23 percent less likely to experience progression, death, or initiation of new therapy compared with patients receiving AVD plus bleomycin.
Inclusion criteria were the following: (i) stage III-C to IV (advanced) mucosal or uveal melanoma, whose diagnosis was histologically confirmed either on the primary tumor or on a metastasis; (ii) patients who received at least one infusion of anti-CTLA-4 or anti-PD-1 mAbs used either as first or second line, between 2008 and 2016; (iii) patients in the chemotherapy subgroup were treated with at least one cycle of chemotherapy, including carboplatin, fotemustine, dacarbazine
, or temozolomide between 2000 and 2016 without further immunotherapy or BRAF or MEK inhibitors; (iv) minimal follow-up of 3 months after the first cycle of treatment in alive patients; and (v) radiologic assessment of tumor response at Week 12 with CT scan.
The majority of the responses with doxorubicin-based regimens were seen in patients receiving the combination of doxorubicin and ifosfamide (4/5 pts) or doxorubicin and dacarbazine
Single agents such as cisplatin or paclitaxel versus combined agents such as the BOLD regimen (bleomycin + vincristine + lomustine + dacarbazine
) plus recombinant interferon alpha 2-b have been studied with no more than 20% response rate (RR) and absence of survival advantages [7, 26].
Notably, ipilimumab-treated metastatic melanoma patients had significantly longer overall survival (OS) than those treated with gp100 vaccination  or combined with dacarbazine
Various anti-cancer drugs such as epidermal growth factor receptor (EGFR) inhibitors including cetuximab and gefitinib, multikinase inhibitors (Imatinib, sorafenib), taxanes (Paclitaxel), vinca alkaloids (Vincristine, vinblastine), antimetabolites (6-mercaptopurine, 5-fluorouracil, Cytarabine, capecitabine, gemcitabine), genotoxic agents (Cisplatin, carboplatin, oxaliplatin, etoposide, cyclophosphamide, and anthracyclines like doxorubicin, daunorubicin, epirubicin), hydroxyurea, cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) and ABVD (Doxorubicin, bleomycin, vinblastine, dacarbazine
) regimens are associated with prominent and sometimes dose-limiting dermatologic complications.