Europe Approves New Nivolumab Dosing Schedules

Fouad Namouni, MD

Fouad Namouni, MD

A 4-week dosing schedule for nivolumab (Opdivo) has been approved by the European Commission for the treatment of patients with advanced melanoma and previously treated renal cell carcinoma (RCC), Bristol-Myers Squibb (BMS), the manufacturer of the PD-1 inhibitor, has announced.

The commission specifically approved a 4-week dosing regimen with 480 mg of nivolumab for these indications. Additionally, the commission approved replacing weight-based dosing with 240 mg every 2 weeks for the 6 nivolumab monotherapy indications approved in the European Union—melanoma, non—small cell lung cancer (NSCLC), RCC, classical Hodgkin lymphoma, head and neck squamous cell carcinoma (HNSCC), and urothelial carcinoma.

“This approval marks a significant achievement in our longstanding commitment to providing patients and healthcare providers with more flexible and convenient treatment options,” Fouad Namouni, MD, head of development, Oncology, BMS, said in a statement. “Bristol Myers-Squibb is dedicated to addressing the unique needs of patients, and with this approval, we will now be able to offer a range of dosing options for an immuno-oncology medicine approved in the European Union.”

In March 2018, the FDA approved a supplemental biologics license application adding the 4-week dosing schedule for nivolumab across several of the PD-1 inhibitor’s indications.

Physicians can now prescribe the new dosing schedule of 480 mg of nivolumab infused every 30 minutes every 4 weeks for these approved indications:

• Metastatic melanoma (monotherapy or monotherapy phase after combination treatment with ipilimumab [Yervoy])
• Previously treated metastatic NSCLC
• Advanced RCC following prior antiangiogenic therapy
• Previously treated locally advanced or metastatic urothelial carcinoma following disease progression during or after platinum-based chemotherapy
• Classical Hodgkin lymphoma following relapse/progression after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or three or more lines of systemic therapy that includes autologous HSCT
• Recurrent/metastatic HNSCC following platinum-based therapy
• Hepatocellular carcinoma after prior sorafenib therapy
• Adjuvant therapy for patients with completely resected melanoma with lymph node involvement or metastatic disease.

Physicians now have the option of using either the new 4-week dosing schedule or the previously approved schedule of 240 mg every 2 weeks, now available in a new 240 mg vial.

Research presented at the 2017 AACR Annual Meeting indicated that safety and efficacy would be similar between a nivolumab dosing schedule of 480 mg every 4 weeks compared with 3 mg/kg every 2 weeks. Using quantitative clinical pharmacology analyses and safety assessments, the investigators examined the predicted risk/benefit profile of the less frequent 480-mg regimen relative to the 3-mg/kg regimen.

Among patients with melanoma, NSCLC, or RCC, there was a <1% difference in the predicted probability of achieving a response. The predicted 1- and 2-year survival probabilities were also similar among patients with these tumor types receiving either of the 2 doses, with differences ranging between 0% to 4.6% at year 1, and 1.9% to 6.9% at year 2.

Reference:

A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res.&nbsp;2017;77(13 Suppl): Abstract CT101. doi:10.1158/1538-7445.AM2017-CT101.