FDA News - March 2018

JHOP - March 2018 Vol 8, No 1 - FDA Approvals, News & Updates

This section provides a brief overview of new cancer drugs or new indications approved by the FDA between January 12 and February 16, 2018.

In This Article


Lynparza First Treatment Approved for Patients with Germline BRCA-Positive Metastatic Breast Cancer

On January 12, 2018, the FDA approved a new indication for olaparib (Lynparza; AstraZeneca) for the treatment of women with deleterious or suspected deleterious germline BRCA-positive, HER2-negative, metastatic breast cancer who received previous chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is the first FDA-approved treatment for this patient population. Like other PARP inhibitors, olaparib was previously approved for the treatment of ovarian cancer.

“This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer. This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

This FDA approval was based on results from the randomized, open-label OlympiAD clinical trial of 302 patients with germline BRCA-positive, HER2-negative, metastatic breast cancer. Patients were randomized based on their previous chemotherapy for metastatic disease, hormone receptor status, and previous platinum-based chemotherapy. The primary end point was progression-free survival (PFS). The median PFS was 7 months with olaparib versus 4.2 months with chemotherapy alone (hazard ratio, 0.58; 95% confidence interval, 0.43-0.80; P = .0009).

The most common (≥20%) adverse reactions reported with olaparib were anemia, nausea, fatigue, vomiting, neutropenia, leukopenia, nasopharyngitis, influenza, respiratory tract infection, diarrhea, arthralgia, myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis.

On the same day, the FDA approved the BRACAnalysis CDx test (Myriad Genetic Laboratories), which is used to identify patients with breast cancer and deleterious or suspected deleterious germline BRCA mutations who may be eligible for treatment with olaparib.

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Gilotrif Receives New Indication as First-Line Treatment for Metastatic NSCLC with Nonresistant EGFR Mutations

On January 12, 2018, afatinib (Gilotrif; Boehringer Ingelheim) received FDA approval as first-line treatment for patients with metastatic non–small-cell lung cancer (NSCLC) associated with nonresistant EGFR mutations as identified via an FDA-approved test. Afatinib received orphan drug status for this indication, and was approved under the FDA priority review process.

Afatinib was previously approved for patients with metastatic NSCLC and EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test, and for patients with metastatic, squamous NSCLC that progressed with platinum-based chemotherapy.

The FDA approval of this new indication for afatinib was based on durable responses in 32 patients with metastatic NSCLC and nonresistant EGFR mutations other than exon 19 deletions or exon 21 L858R substitutions. The patients were enrolled in 1 of 3 clinical trials, and received afatinib 40 mg or 50 mg, orally, once daily.

The overall response rate was 66% (95% confidence interval, 47-81); among the 21 patients who responded to treatment, the response lasted ≥12 months in 52% of patients and ≥18 months in 33% of patients.

The most common (≥20%) adverse reactions reported with afatinib were diarrhea, rash, acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, and pruritus.

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Lutathera First Radioactive Drug Approved for Adults with Gastroenteropancreatic Neuroendocrine Tumors

On January 26, 2018, the FDA approved lutetium Lu 177 dotatate (Lutathera; Advanced Accelerator Applications), a radioactive drug, for the treatment of adults with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Lutetium Lu 177 dotatate was approved under the FDA’s priority review process, and was designated as an orphan drug.

This is the first approval of a radioactive drug for the treatment of patients with GEP-NETs. This radioactive drug works by binding to a somastatin receptor on the tumor, allowing the radiation to destroy the cancerous cells.

“GEP-NETs are a rare group of cancers with limited treatment options after initial therapy fails to keep the cancer from growing. This approval provides another treatment choice for patients with these rare cancers. It also demonstrates how the FDA may consider data from therapies that are used in an expanded access program to support approval for a new treatment,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

This approval was based on the results of 2 clinical trials. The first was a study of 229 patients with a particular type of advanced somatostatin receptor–positive GEP-NET who were randomized to lutetium Lu 177 dotatate plus octreotide or octreotide monotherapy. The end point was progression-free survival, which was longer in patients who received lutetium Lu 177 dotatate plus octreotide than in those who received octreotide monotherapy, translating to a lower risk for death or tumor growth in those who received the combination versus monotherapy.

The second study included 1214 patients with somato­statin receptor–positive tumors, including GEP-NETs. Among a subgroup of 360 patients with GEP-NETs who received lutetium Lu 177 dotatate and were assessed by the FDA, 16% had complete or partial response.

The common side effects associated with lutetium Lu 177 dotatate include lymphopenia, high enzyme levels in certain organs, vomiting, nausea, hyperglycemia, and hypokalemia. Serious side effects include myelosuppression, secondary myelodysplastic syndrome, leukemia, renal toxicity, hepatotoxicity, neuroendocrine hormonal crises, and infertility.

Patients receiving lutetium Lu 177 dotatate are exposed to radiation, which may cause harm to a developing fetus and to other people.

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Zytiga Receives New Indication, with Prednisone, for Metastatic, High-Risk Castration-Sensitive Prostate Cancer

On February 7, 2018, abiraterone acetate (Zytiga; Janssen Biotech) received FDA approval for use, in combination with prednisone, for the treatment of patients with metastatic, high-risk castration-sensitive prostate cancer (CSPC). The FDA approved this new indication under its priority review program.

The combination of abiraterone acetate plus prednisone was previously approved for the treatment of patients with metastatic, castration-resistant prostate cancer (CRPC), including patients who had received chemotherapy and patients with newly diagnosed metastatic CRPC.

This expanded FDA approval was based on the results of the international, placebo-controlled, LATITUDE clinical trial that included 1199 patients with metastatic, high-risk CSPC. Patients were randomized to abiraterone acetate 1000 mg plus prednisone 5 mg once daily (N = 597) or to placebo (N = 602). All patients received a gonadotropin-releasing hormone or had a bilateral orchiectomy. The primary end point was overall survival (OS). The median OS could not be reached in the abiraterone acetate plus prednisone arm, and was 34.7 months in the placebo arm (hazard ratio [HR], 0.621; 95% confidence interval [CI], 0.509-0.756; P <.0001). Similarly, the median time to chemotherapy initiation was not reached in the combination arm versus 38.9 months in the placebo arm (HR, 0.44; 95% CI, 0.35-0.56; P <.0001).

The most common (≥5%) adverse reactions with abiraterone acetate in the LATITUDE study were hypertension, hot flush, hypokalemia, increased alanine aminotransferase, increased aspartate aminotransferase, headache, urinary tract infection, upper respiratory tract infection, and cough.

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Erleada First Therapy Approved for Patients with Nonmetastatic Castration-Resistant Prostate Cancer

On February 14, 2018, apalutamide (Erleada; Janssen Pharmaceuticals), an androgen receptor inhibitor, received accelerated approval by the FDA for the treatment of patients with nonmetastatic, castration-resistant prostate cancer (CRPC). Apalutamide is the first treatment approved by the FDA for patients with nonmetastatic CRPC, and was approved under the FDA priority review process.

“This approval is the first to use the endpoint of metastasis-free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

“In the trial supporting approval, Erleada had a robust effect on this endpoint. This demonstrates the agency’s commitment to using novel endpoints to expedite important therapies to the American public,” Dr Pazdur added.

The approval of apalutamide was based on data from a single clinical trial that included 1207 patients with nonmetastatic CRPC who were randomized to apalutamide or a placebo. All patients also received gonadotropin-releasing hormone analog therapy or surgical castration.

The primary end point was metastasis-free survival. The median metastasis-free survival was 40.5 months among patients who received apalutamide versus 16.2 months in patients who received a placebo—more than double the difference.

The common (≥10%) side effects reported with apalutamide include fatigue, hypertension, rash, diarrhea, nausea, weight loss, arthralgia, falls, hot flushes, decreased appetite, fractures, and peripheral edema. Severe side effects include falls, fractures, and seizures.

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Imfinzi First Treatment Approved to Reduce Disease Progression in Unresectable Stage III NSCLC After Chemoradiation

On February 16, 2018, the FDA approved an expanded indication for durvalumab (Imfinzi; AstraZeneca), a PD-L1 inhibitor, for the treatment of patients with unresectable stage III non–small-cell lung cancer (NSCLC) that did not progress after chemoradiation. Durvalumab received accelerated approval in 2017 for the treatment of certain patients with metastatic or locally advanced bladder cancer.

“This is the first treatment approved for stage III unresectable non-small cell lung cancer to reduce the risk of the cancer progressing, when the cancer has not worsened after chemoradiation. For patients with stage III lung cancer that cannot be removed surgically, the current approach to prevent progression is chemoradiation,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

“Although a small number of patients may be cured with the chemoradiation, the cancer may eventually progress. Patients now have an approved therapy that has been shown to keep the cancer from progressing for a longer time after chemoradiation,” Dr Pazdur added.

This new indication for durvalumab was based on data from a clinical trial comprising 713 patients with NSCLC that did not progress postchemoradiation. Patients were randomized to receive durvalumab or placebo. The median progression-free survival was 16.8 months with durvalumab versus 5.6 months with placebo. The overall survival rates are still pending, and will be provided to the FDA postmarketing by the sponsor.

The common side effects associated with durvalumab in patients with unresectable stage III NSCLC include cough, fatigue, pneumonitis, upper respiratory tract infections, dyspnea, and rash. Serious side effects include pneumonitis, hepatitis, colitis, endocrinopathies, and nephritis, as well as infection and infusion-­related reactions.

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Last modified: April 24, 2018