FDA Expands Opdivo Label to Include Bladder Cancer

Decision based on positive phase 2 data

The FDA has approved nivolumab (Opdivo, Bristol-Myers Squibb) intravenous (IV) injection for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or after platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

This indication received accelerated approval based on tumor response rate and the duration of response. Continued approval for this indication may be contingent on verification and description of clinical benefit in confirmatory trials.

Nivolumab is a programmed death receptor-1 (PD-1)-blocking antibody. The recommended dose for patients with mUC is 240 mg administered as an IV infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity occurs.

The FDA’s decision was based on data from the CheckMate-275 trial, a phase 2, open-label, single-arm, multicenter study of nivolumab in patients with locally advanced or mUC who had disease progression during or after treatment with a platinum-containing chemotherapy or had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. In this study, 270 patients received nivolumab 3 mg/kg IV every two weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was the confirmed objective response rate (ORR), as defined by an independent radiographic review committee. The patients’ median age was 66 years (range: 38 to 90 years). Some patients (29%) had received two or more systemic regimens in the metastatic setting before enrolling in the study. Patients were included in the trial regardless of their programmed death ligand-1 (PD-L1) status.

Efficacy was evaluated in 270 patients with six months’ follow-up. Nivolumab demonstrated an ORR of 19.6%. The percentage of patients with a complete response was 2.6%, and the percentage of patients with a partial response was 17.0%. Among responders, the median duration of response was 10.3 months (range: 1.9 to 12.0 months). The median time to response was 1.9 months (range: 1.6 to 7.2 months).The most common adverse events included fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%).

Nivolumab is associated with several warnings and precautions, including immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, and encephalitis, along with infusion reactions and embryo-fetal toxicity.

Nivolumab is now indicated for the treatment of patients with:

  • BRAF V600 mutation-positive unresectable or metastatic melanoma as a single agent
  • BRAF V600 wild-type unresectable or metastatic melanoma as a single agent
  • Unresectable or metastatic melanoma in combination with ipilimumab (Yervoy, Bristol-Myers Squibb)
  • Metastatic non–small-cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy
  • Advanced renal cell carcinoma (RCC) after anti-angiogenic therapy
  • Classical Hodgkin’s lymphoma that has relapsed or progressed after autologous hematopoietic stem-cell transplantation (HSCT) and post-transplantation brentuximab vedotin (Adcetris, Seattle Genetics)
  • Recurrent or metastatic squamous-cell carcinoma of the head and neck with disease progression during or after platinum-based therapy
  • Locally advanced or metastatic urothelial carcinoma with disease progression during or after platinum-containing chemotherapy or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

Source: Bristol-Myers Squibb; February 2, 2017.