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Rolapitant IV Approved for Delayed Nausea & Vomiting Associated With Chemotherapy

The FDA has approved rolapitant IV in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

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Rolapitant is a highly selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV). With a long plasma half-life of approximately 7 days, a single dose of rolapitant, as part of an antiemetic regimen, significantly improved complete response rates in the delayed phase of CINV.


Results from three phase III trials of rolapitant oral tablets demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens. In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy. Results from a bioequivalence trial demonstrated comparability of the IV and oral formulations of rolapitant.


Rolapitant IV is supplied in ready-to-use vials and does not require refrigerated storage or mixing. As a result, utilization in busy chemotherapy clinics is straightforward and easily adopted into existing practice patterns for administration of antiemetic regimens associated with emetogenic chemotherapy. The treatment is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone, a CYP3A4 substrate, and rolapitant is the first IV administered NK-1 receptor antagonist approved by the FDA that does not contain polysorbate 80.


"Many health care providers tend to believe that CINV is no longer an unmet need, but the reality is that more than half of patients treated with emetogenic chemotherapy experience delayed CINV, even when prescribed standard preventative therapies, such as a 5-HT3 receptor antagonist and dexamethasone," said Lee Schwartzberg, MD, FACP, Professor of Medicine at University of Tennessee Health Science Center. "The FDA approval of [rolapitant] IV gives doctors and nurses a new option to help protect their patients from these often preventable side effects."


Cemiplimab Granted Breakthrough Therapy Designation for Advanced CSCC

The FDA has granted Breakthrough Therapy designation status to cemiplimab for the treatment of adults with metastatic cutaneous squamous cell carcinoma (CSCC) and adults with locally advanced and unresectable CSCC.


Positive, preliminary results for cemiplimab were reported from two expansion cohorts involving 26 advanced CSCC patients in a phase I study of nearly 400 patients, at the 2017 ASCO Annual Meeting. EMPOWER-CSCC 1, a phase II, potentially pivotal, single-arm, open-label clinical trial of cemiplimab is currently enrolling patients with metastatic CSCC and locally advanced and unresectable CSCC.


CSCC is the second most common type of skin cancer in the U.S. Although CSCC has a good prognosis when caught early, it can prove especially difficult to treat when it progresses to advanced stages. Patients at this stage can be disfigured due to multiple surgeries to remove CSCC tumors on the head, neck, and other parts of the body. CSCC is responsible for the most deaths among non-melanoma skin cancer patients.


New Dosing of Brigatinib Approved for ALK+ Non-Small Cell Lung Cancer

The FDA has approved the supplemental new drug application (sNDA) for brigatinib 180 mg tablets. Brigatinib received Accelerated Approval from the FDA in April 2017 for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.


This indication is approved under Accelerated Approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The recommended dosing regimen for brigatinib is 90 mg orally once daily for the first 7 days and if tolerated, the dose is then increased to 180 mg orally once daily.


"Today's approval of the [brigatinib] 180 mg tablets will reduce pill burden for patients taking [this drug] for advanced ALK+ NSCLC," said Mohammad Jahanzeb, MD, FACP, Professor of Clinical Medicine, Hematology and Oncology at University of Miami's Miller School of Medicine. "As a physician, having a 180 mg tablet available for my patients may help them better manage their treatment schedule."


The recommended dosing regimen was supported by the results of the pivotal phase II ALTA (ALK in Lung Cancer Trial of AP26113) trial. This two-arm, open-label, multicenter trial of 222 patients with locally advanced or metastatic ALK+ NSCLC who had progressed on crizotinib found that, of the patients who received the recommended dosing regimen (90->180 mg), 53 percent achieved a confirmed objective response (OR) as assessed by an Independent Review Committee (IRC).


Additionally, 67 percent of patients with measurable brain metastases who received this dosing regimen achieved a confirmed intracranial OR by IRC assessment. In ALTA, serious adverse reactions occurred in 38 percent of patients in the 90 mg group and 40 percent of patients in the 90->180 mg group. Overall, the most common serious adverse reactions were pneumonia and interstitial lung disease/pneumonitis. Fatal adverse reactions occurred in 3.7 percent of patients and consisted of pneumonia (two patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urosepsis (one patient each). At the recommended dosing regimen, the most common adverse reactions (>=25%) with brigatinib were nausea, diarrhea, fatigue, cough, and headache. The ALTA trial is ongoing.


Dasatinib Approval Expanded to Include Treatment of Children With Ph+ CML

The FDA has expanded the indication for dasatinib tablets to include the treatment of children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).


This approval was granted under priority review, and the indication received Orphan Drug Designation from the FDA. The safety and efficacy of dasatinib in pediatric patients was evaluated in two pediatric studies of 97 patients with CP-CML: an open-label, non-randomized, dose-ranging trial (NCT00306202) and an open-label, non-randomized, single-arm trial (NCT00777036). Among the 97 patients in the two studies, 51 patients (exclusively from the single-arm trial) had newly diagnosed CP-CML, and 46 patients (17 from the dose-ranging trial and 29 from the single-arm trial) were resistant or intolerant to previous treatment with imatinib. The majority of patients were treated with dasatinib tablets 60 mg/m2 once daily. Patients were treated until disease progression or unacceptable toxicity.


After 24 months of treatment, 96.1 percent of newly diagnosed patients (95% CI: 86.5, 99.5) and 82.6 percent of patients resistant or intolerant to imatinib (95% CI: 68.6, 92.2) had complete cytogenic response (CCyR). With a median follow-up of 4.5 years in newly diagnosed patients and 5.2 years in imatinib-resistant or imatinib-intolerant patients, the median durations of CCyR, major cytogenic response, and major molecular response could not be estimated as more than half of the responding patients had not progressed at the time of data cutoff.


Adverse reactions reported in >=10 percent of dasatinib-treated pediatric patients (n=97) were headache, nausea, diarrhea, skin rash, vomiting, pain in extremity, abdominal pain, fatigue, and arthralgia.


"Options for pediatric patients with chronic myeloid leukemia are limited, and it is challenging to conduct clinical trials investigating potential new treatments in this small patient population," said Lia Gore, MD, University of Colorado School of Medicine and Children's Hospital Colorado. "Dasatinib is an important new option to help address the unmet needs of children with Philadelphia chromosome-positive CML in chronic phase."