FDA News

This section provides a brief overview of new cancer drugs or new indications approved by the FDA between March 2 and March 27, 2020.

• FDA Approves Imfinzi as First-Line Treatment, with Chemotherapy, for Extensive-Stage Small-Cell Lung Cancer
• FDA Approves Opdivo plus Yervoy for Hepatocellular Carcinoma
• Sarclisa Newest Treatment Approved by the FDA for Patients with Multiple Myeloma

FDA Approves Imfinzi as First-Line Treatment, with Chemotherapy, for Extensive-Stage Small-Cell Lung Cancer

On March 27, 2020, the FDA approved a new indication for the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca), in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC). Imfinzi was previously approved by the FDA for the treatment of patients with metastatic urothelial cancer and for patients with unresectable, stage III non–small-cell lung cancer. The FDA granted durvalumab an orphan drug designation for this new indication.

The approval of this new combination was based on the CASPIAN study, a randomized, multicenter, active-controlled, open-label, clinical trial. The study included patients with treatment-naïve ES-SCLC who were randomized to durvalumab plus chemotherapy or to chemotherapy alone.

The major efficacy outcome measure was overall survival (OS). The secondary outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR), per RECIST v1.1.

At a median follow-up of 14 months, the median OS was 13 months (95% confidence interval [CI], 11.5-14.8) in the durvalumab plus chemotherapy arm versus 10.3 months (95% CI, 9.3-11.2) in the chemotherapy-alone arm (hazard ratio, 0.73; 95% CI, 0.59-0.91; P = .0047).

The median PFS (by investigator assessment) was 5.1 months (95% CI, 4.7-6.2) in the durvalumab plus chemotherapy arm and 5.4 months (95% CI, 4.8-6.2) in the chemotherapy-alone arm. The investigator-assessed confirmed ORR was 68% (95% CI, 62%-73%) in the durvalumab-based combination arm and 58% (95% CI, 52%-63%) in the chemotherapy-alone arm.

The most common (≥20%) adverse events in patients with ES-SCLC in this study were nausea, fatigue/asthenia, and alopecia.

For patients with ES-SCLC, durval­umab treatment should be administered before chemotherapy, on the same day.

FDA Approves Opdivo plus Yervoy for Hepatocellular Carcinoma

On March 10, 2020, the FDA accelerated the approval of the immunotherapy combination of nivolumab (Opdivo; Bristol-Myers Squibb) plus ipilimumab (Yervoy; Bristol-Myers Squibb) for patients with hepatocellular carcinoma (HCC) who have previously received sorafenib. Nivolumab and ipilimumab have been previously approved by the FDA for several indications. This new indication was previously granted a breakthrough therapy designation.

The efficacy of the combination was investigated in cohort 4 of the CheckMate-040 study, a multicenter, multi-cohort, open-label clinical trial conducted in patients with HCC whose disease progressed while receiving or who were intolerant of sorafenib. A total of 49 patients received nivolumab 1 mg/kg in combination with ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by monotherapy with nivolumab 240 mg every 2 weeks, until disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate (ORR) and duration of response as determined by blinded independent central review using RECIST v1.1. The ORR was 33% (95% confidence interval, 20-48), with 4 complete responses and 12 partial responses. The duration of response ranged from 4.6 months to >30.5 months, with 31% of responses lasting ≥24 months.

The most common (≥20%) adverse reactions with the drug combination were fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness.

For patients with HCC, the recommended doses are nivolumab 1 mg/kg, followed by ipilimumab 3 mg/kg on the same day, every 3 weeks for 4 doses, then nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks.

Sarclisa Newest Treatment Approved by the FDA for Patients with Multiple Myeloma

On March 2, 2020, the FDA approved isatuximab-irfc (Sarclisa; Sanofi-Aventis), a CD38-directed cytolytic antibody, for the treatment of adults with multiple myeloma, for use in combination with pomalidomide (Pomalyst) and dexamethasone, in patients who had received at least 2 therapies that include lenalidomide (Revlimid) and a proteasome inhibitor. The FDA granted isatuximab an orphan drug designation.

“Targeting cells has led to the development of important oncology treatments. While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he said.

According to the National Cancer Institute, an estimated 32,270 new cases of multiple myeloma will be diagnosed in the United States in 2020 and 12,830 people will die of the disease. Although many new treatments were approved by the FDA for multiple myeloma in the past decade, the disease often relapses or becomes refractory to a specific therapy.

The FDA approval of isatuximab was based on a multicenter, multinational, randomized, open-label, 2-arm, phase 3 clinical trial that included 307 patients with relapsed or refractory multiple myeloma. All patients had received 2 or more previous therapies, which included lenalidomide and a proteasome inhibitor. The patients were randomized in a 1:1 ratio to the 3-drug combination of isatuximab plus pomalidomide and low-dose dexamethasone or to the 2-drug combination of pomalidomide plus low-dose dexamethasone.

The primary end point was progression-free survival (PFS). The improved PFS with the isatuximab-based regimen included a 40% risk reduction in disease progression or death versus the patients who received pomalidomide and low-dose dexamethasone alone (hazard ratio, 0.596; 95% confidence interval [CI], 0.44-0.81; P = .001). The median PFS with the 3-drug regimen with isatuximab was 11.53 months (95% CI, 8.94-13.9) versus 6.47 months with the 2-drug combination (95% CI, 4.47-8.28), respectively. The overall response rates were 60.4% and 35.5%, respectively.

The most common (≥20%) adverse reactions were neutropenia, infusion-­related reactions, pneumonia, upper respiratory tract infection, and diarrhea. In patients with grade 3 or 4 side effects, including infusion-related reactions, isatuximab should be permanently discontinued.

The recommended dose of isatuximab is 10 mg/kg, administered as an intravenous infusion every week for 4 weeks, then every 2 weeks in combination with pomalidomide and dexamethasone, until disease progression or unacceptable toxicity.