Friday, Sept. 22, 2017
From the Society for Immunotherapy of Cancer
In cooperation with the Food and Drug Administration (FDA), and as a service to our members, SITC will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields of recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, SITC does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On September 22, 2017, the Food and Drug Administration granted accelerated approval to nivolumab (OPDIVO, Bristol-Myers Squibb Co.) for the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib.
Approval was based on a 154-patient subgroup of CHECKMATE-040 (NCT 01658878), a multicenter, open-label trial conducted in patients with HCC and Child-Pugh A cirrhosis who progressed on or were intolerant to sorafenib. In addition to including patients without active hepatitis viral infection, the trial enrolled patients with either active HBV (31%) or HCV (21%) but not those with active co-infection with HBV and HCV or with hepatitis D virus infection. Patients received nivolumab 3 mg/kg by intravenous infusion every 2 weeks. The confirmed overall response rate, as assessed by blinded independent central review using RECIST 1.1, was 14.3% (95% CI: 9.2, 20.8), with 3 complete responses and 19 partial responses. Response duration ranged from 3.2 to 38.2+ months; 91% of responders had responses lasting 6 months or longer and 55% had responses lasting 12 months or longer.
Common adverse reactions occurring in greater than 20% of patients in nivolumab clinical trials include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia. Adverse reactions occurring in patients with HCC in CHECKMATE-040 were similar to those previously reported in product labelling, with the exception of a higher incidence of elevations in transaminases and bilirubin levels. Treatment with nivolumab resulted in treatment-emergent grade 3 or 4 AST in 27 (18%) patients, grade 3 or 4 ALT in 16 (11%) patients, and grade 3 or 4 bilirubin in 11 (7%) of patients. Immune-mediated hepatitis requiring systemic corticosteroids occurred in 8 (5%) patients.
The recommended nivolumab dose for HCC treatment is 240 mg every 2 weeks.
Full dosing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125554s041lbl.pdf.
FDA granted priority review to nivolumab for this indication. As a condition of accelerated approval, further trials will be required to verify the clinical benefit of nivolumab for this indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).