FDA News – November 2016

November 2016, Vol 6, No 11 - FDA News


In This Article




Tecentriq First PD-L1 Approved for Metastatic NSCLC with EGFR or ALK mutations

On October 19, 2016, the FDA approved atezolizumab (Tecentriq; Genentech Oncology), a PD-L1–blocking antibody, 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 genetic mutations should have disease progression after taking an FDA-approved therapy for these mutations before receiving atezolizumab. This is the first PD-L1 inhibitor approved for patients with metastatic NSCLC.

“The approval of Tecentriq is another important step for patients by increasing the number of medicines available to people living with lung cancer,” said Bonnie J. Addario, a lung cancer survivor and founder of the Bonnie J. Addario Lung Cancer Foundation.

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

The most common (≥20%) adverse events in patients who received 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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Lartruvo First Therapy Approved for Soft-Tissue Sarcoma in 40 Years

On October 19, 2016, the FDA granted olaratumab (Lartruvo; Eli Lilly) accelerated approval for use in combination with doxorubicin for the treatment of patients with soft-tissue sarcoma and 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. 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 overall response rate 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 a fast track designation, breakthrough therapy designation, priority review designation, and an orphan drug designation for this indication.

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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; Merck) for the first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors express high PD-L1 levels (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 checkpoint inhibitor to receive FDA approval as first-line treatment of metastatic NSCLC.

In addition, the FDA converted the previously accelerated approval of pembrolizumab for the second-line treatment of NSCLC to a 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 an FDA-approved therapy for these mutations before receiving pembrolizumab.

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

In a study of 305 patients who had not received treatment for metastatic NSCLC, the median PFS was 10.3 months in the pembrolizumab group versus 6 months in the chemotherapy group. Furthermore, an interim analysis demonstrated a significant improvement in OS with pembro­lizumab versus chemotherapy.

In a study of 1033 patients who previously received treatment for metastatic NSCLC, the OS was better in the pembrolizumab 2-mg/kg group or 10-mg/kg group compared with the docetaxel group. The me­dian survival 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 reported with pembro­lizumab in patients with metastatic NSCLC 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 therapy included immune-mediated pneumonitis, colitis, hepatitis, endo­crinopathies, and nephritis.

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Use of Screening Tests for Ovarian Cancer Not Supported by the FDA

On September 7, 2016, the FDA recommended against the use of ovarian cancer screening tests and alerted women to the associated risks of using them. The FDA cited particular concern for the delay in providing effective preventive care to women who are asymptomatic but are still at increased risk for ovarian cancer.

Although screening tests for breast, colon, and cervical cancers are effective for early detection and for prevention of cancer-related deaths, no valid data support the use of any test, including those approved by the FDA for other uses, as a screening tool for ovarian cancer.

Tests currently marketed as ovarian cancer screening tests have not demonstrated accuracy or reliability in screening asymptomatic women for early ovarian cancer, according to available data from clinical trials, professional healthcare society recommendations, and the US Preventive Services Task Force.

Because the use of unverified ovarian cancer screening tests may be harmful for women who are at increased risk for ovarian cancer (eg, neglecting to take appropriate actions to reduce their future risk because test results demonstrate that no cancer is currently present), the FDA advises that such tests should not be used by women at increased risk for ovarian cancer.

The FDA recommends that women (including those with an increased risk for ovarian cancer) not depend on ovarian cancer screening test results when making treatment decisions; discuss ways for reducing their risk for ovarian cancer with their physician (especially if they have a family history of the disease or have the BRCA1 or BRCA2 mutations); and note that there are currently no safe and effective ovarian cancer screening tests available.

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