May 17, 2016 –
Do targeted therapies diminish market volumes? Not necessarily, as we can nicely learn from the example of Nivolumab (Opdivo). While initially the targeted development of a drug (Nivolumob (Opdivo) in this case) may lead to a somewhat restricted use of a drug in a targeted and selected patient subgroup, extending the indications in which the drug in question may be of benefit for patients may lead to a remarkable expansion of the eligible patient basis. Thus, Nivolumab (Opdivo
) was first approved for the treatment of patients with BRAF V600 wild-type un-resectable or metastatic melanoma followed by indications such as metastatic squamous and non-squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy and advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
The American Food & Drug Administration (FDA) just approved Nivolumab (Opdivo) for yet another indication, namely the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation Brentuximab Vedotin (Adcetris).
This newest approval of Nivolumab (Opdivo) was based on two single-arm, multicenter trials in adults with relapsed or refractory cHL. The trials enrolled patients regardless of PD-L1 expression status on Reed-Sternberg cells. The primary efficacy endpoint was objective response rate (ORR) as determined by an independent radiographic review committee. Additional outcome measures included duration of response (DOR). Efficacy was evaluated in 95 patients previously treated with autologous HSCT and post-transplantation brentuximab vedotin. Patients had a median of 5 prior systemic regimens (range: 3, 15) and received a median of 17 doses of nivolumab (range: 3, 48). Single-agent nivolumab produced a 65% ORR (95% CI: 55%, 75%), with 58% partial remission and 7% complete remission. The median time-to-response was 2.1 months (range: 0.7 to 5.7 months). The estimated median DOR was 8.7 months.
Clinical safety was evaluated in 263 patients with relapsed or refractory cHL. Ninety-eight per cent of patients had received autologous HSCT. Patients received a median of 10 doses of nivolumab (range: 1, 48) at the approved dose-schedule. The most common (reported in at least 20%) adverse reactions of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea. Additional common adverse reactions (reported in at least 10%) included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis. Other immune-mediated adverse reactions, occurring in 1% to 5% of patients, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. Serious adverse reactions were reported in 21% of patients. The most common SAEs, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.
In context of this new indication, a new “Warning and Precaution” was issued for complications of allogeneic HSCT after Nivolumab (Opdiva) treatment, however. Transplant-related deaths have occurred, and health care professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions. FDA has required the manufacturer to further study the safety of allogeneic HSCT after Nivolumab (Opdiva). Moreover, continued approval for the cHL indication may be contingent upon verification of clinical benefit through a randomized phase 3 trial.