FDA News: November 2016

Online First - FDA Approvals, Online First

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Tecentriq Approved by the FDA for Metastatic NSCLC

On October 18, 2016, the FDA approved atezolizumab (Tecentriq), a PD-L1 inhibitor, for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) that progressed during or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression after using FDA-approved therapies for these aberrations before receiving atezolizumab.

The FDA approval of atezolizumab was based on the OAK and POPLAR clinical trials. These 2 international, randomized, open-label studies involved 1137 patients with NSCLC. The median overall survival (OS) in the OAK study was 13.8 months in patients receiving atezo­lizumab versus 9.6 months in patients receiving docetaxel. In addition, the OS in the POPLAR study was 12.6 months in the atezolizumab group compared with 9.7 months in the docetaxel group.

The most common (≥20%) adverse events with atezolizumab included fatigue (46%), decreased appetite (35%), dyspnea (32%), nausea (22%), musculoskeletal pain (22%), and constipation (20%). The most common (≥2%) grade 3 or 4 adverse reactions included dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, increase in aspartate aminotransferase levels, increase in alanine aminotransferase levels, dysphagia, and arthralgia.

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Keytruda Receives New FDA Indication for First-Line Treatment of Metastatic NSCLC

On October 24, 2016, the FDA approved pembrolizumab (Keytruda) for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%) as determined by an FDA-approved test, with no EGFR or ALK mutations, and no previous systemic chemotherapy treatment for metastatic NSCLC. This is the first PD-1 inhibitor to receive FDA approval as first-line treatment for this patient population.

In addition, the FDA converted the previously accelerated approval of pembrolizumab for the second-line treatment of NSCLC to regular approval. For this indication, the FDA approved pembrolizumab for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%), as determined by an FDA-approved test, with disease progression during or after platinum-­containing chemotherapy. Patients with EGFR or ALK mutations should have disease progression while taking FDA-approved therapy for these mutations before receiving pembrolizumab.

These approvals were based on 2 randomized controlled trials that demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) for patients who received pembrolizumab versus chemotherapy.

In a trial of 305 treatment-naïve patients with metastatic NSCLC, the median PFS was 10.3 months with pembrolizumab versus 6 months with chemotherapy.

In a trial of 1033 patients who had received treatment for metastatic NSCLC, the OS was better with pembrolizumab 2 mg/kg or 10 mg/kg compared with docetaxel. The median OS was 10.4 months with pembrolizumab 2 mg/kg, 12.7 months with pembrolizumab 10 mg/kg, and 8.5 months with docetaxel.

The most common (≥15%) adverse events with pembrolizumab included decreased appetite (25%), fatigue (25%), dyspnea (23%), nausea (20%), cough (19%), rash (17%), and constipation (15%). Rare or serious adverse events associated with pembrolizumab included immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.

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Lartruvo First Drug in 40 Years to Receive FDA Approval for Soft-Tissue Sarcoma

On October 19, 2016, the FDA granted olaratumab (Lartruvo) accelerated approval for the treatment, in combination with doxorubicin, of patients with soft-tissue sarcoma with a histologic subtype for which an anthracycline-­containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.

Olaratumab is a platelet-derived growth factor receptor-alpha blocking antibody that works by blocking receptors that cause tumor growth.

“This is the first new therapy approved by the FDA for the initial treatment of soft tissue sarcoma since doxorubicin’s approval more than 40 years ago,” said Richard Pazdur, MD, FDA’s Director of the Office of Hematology and Oncology Products.

Olaratumab’s approval for soft-tissue sarcoma was based on a randomized clinical trial involving 133 patients with more than 25 subtypes of metastatic soft-tissue sarcoma who were randomized to receive olaratumab plus doxorubicin or doxorubicin alone. The study end points included overall survival, progression-free survival (PFS), and overall response rate (ORR). Patients who received olaratumab plus doxorubicin had a median survival of 26.5 months versus 14.7 months for patients who received doxorubicin alone. The PFS was 8.2 months with olaratumab plus doxorubicin versus 4.4 months with doxorubicin alone. Furthermore, the ORR was 18.2% with olaratumab plus doxorubicin versus 7.5% with doxorubicin alone.

The most common (≥20%) adverse events reported with olaratumab plus doxorubicin included nausea (73%), fatigue (69%), neutropenia (65%), musculoskeletal pain (64%), mucositis (53%), alopecia (52%), vomiting (45%), diarrhea (34%), decreased appetite (31%), abdominal pain (23%), neuropathy (22%), and headache (20%). Olaratumab has serious risks, including infusion-related reactions and embryo-fetal harm. Infusion-related reactions include low blood pressure, fever, chills, and rash.

Olaratumab received fast track designation, breakthrough therapy designation, priority review designation, and orphan drug designation for this indication.

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FDA Revises the Indication for Tarceva for Treatment of NSCLC

On October 18, 2016, the FDA updated the indication of erlotinib (Tarceva) for non–small-cell lung cancer (NSCLC) to limit its use to patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test, in patients with NSCLC who are receiving first-line, maintenance, or second-line or more treatment after disease progression with ≥1 chemotherapy regimens. Erlotinib’s initial indication for NSCLC included patients with exon 19 deletions or exon 21 substitution mutations who are receiving first-line treatment only.

This revision reflects the results of the IUNO clinical trial that included 643 patients with advanced NSCLC whose disease did not progress after platinum-based, first-line chemotherapy who did not have EGFR mutations. Patients were randomized to erlotinib or to placebo. The overall survival and progression-free survival were not superior with erlotinib versus placebo.

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FDA Awards $23 Million Worth of Grants to Encourage Drug Development for Rare Diseases

On October 17, 2016, the FDA announced that it awarded 21 clinical research grants worth more than $23 million to principal investigators from academia and industry to increase the development of drugs, biologics, medical devices, or medical foods for patients with rare diseases. The grants were awarded through the Orphan Products Clinical Trials Grants Program, which has funded more than 590 new clinical studies since 1983.

The grants are intended to support clinical trials that evaluate the safety and efficacy of drugs and devices that could potentially obtain FDA approval.

“The grants awarded this year will support much-needed research in 21 different rare diseases, many of which have little, or no, available treatment options,” said Gayatri R. Rao, MD, JD, FDA’s Director of Office of Orphan Product Development, within the Office of Special Medical Programs.

Overall, 24% of the new grant awards fund cancer studies, and 40% of these studies focus on devastating forms of brain cancer—all of which is consistent with the National Cancer Moonshot Initiative to fast-track cancer research.

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Last modified: November 15, 2016
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