US Food and Drug Administration.

After completing this course, the reader will be able to:1. Add vorinostat to the armamentarium of drugs for CTCL.2. Identify the mechanism of action of vorinostat.3. Identify goals of therapy of CTCL.4. Identify active CTCL therapies. Identify CTCL response criteria.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACT

This article summarizes key review findings that supported the approval of tocilizumab for treatment of severe or life‐threatening CAR T cell‐induced cytokine release syndrome.

The FDA approved pembrolizumab on May 23, 2017, for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H), or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and for the treatment of unresectable or metastatic MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The FDA granted the approval based on an understanding of the biology of MSI-H/dMMR across different tumors along with the clinically important effects on overall response rate (ORR) observed in patients who were enrolled in 1 of 5 single-arm clinical trials. The ORR was 39.6% among 149 patients with 15 different tumor types (95% confidence interval, 31.7-47.9), with a 7% complete response rate. The duration of response ranged from 1.6þ months to 22.7þ months, with 78% of responses lasting !6 months. Overall, the adverse event profile of pembrolizumab was similar to the adverse event profile observed across prior trials that supported the approval of pembrolizumab in other indications. This approval of pembrolizumab is the first time that the FDA has approved a cancer treatment for an indication based on a common biomarker rather than the primary site of origin.

Bortezomib (formerly PS-341), a promising new drug for the treatment of multiple myeloma, recently received accelerated approval from the U.S. Food and Drug Administration (FDA) for the therapy of patients with progressive myeloma after previous treatment. Two phase II studies of bortezomib used the same schedule of twice-weekly i.v. dosing for the first 2 weeks of each 3-week cycle. In a randomized study of 54 patients, two doses were compared (1.0 and 1.3 mg/m 2 ) and objective responses occurred at both dose levels (23% versus 35%), including one complete response in each arm. In the other phase II study, 202 heavily pretreated patients (median of six prior therapies) all received the same schedule at 1.3 mg/m 2 . Of 188 evaluable patients, complete responses occurred in five (3%) and partial responses occurred in 47 (25%). The median duration of response was 365 days. The most clinically relevant adverse events were asthenic conditions, nausea, vomiting, diarrhea, thrombocytopenia, and a peripheral neuropathy that often was painful. This report highlights the FDA analysis supporting the accelerated approval. The Oncologist 2003;8:508-513 The Oncologist 2003;8:508-513 www.TheOncologist.comCorrespondence: Robert C. Kane, M.D., F.A.C.P., U.S. FDA, HFD-150, 5600 Fishers Lane, Rockville, Maryland 20857, USA. Telephone: 301-594-2473; Fax: 301-594-0499; e-mail kaner@cder.fda.gov Received September 18, 2003; accepted for publication October 14, 2003. ©AlphaMed Press 1083-7159/2003 The Oncologist ® FDA Commentary LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss the rationale and requirements for accelerated cancer drug approval by the U.S. Food and Drug Administration (FDA). 4. Explain the mechanism of action of bortezomib and its role in cancer treatment.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S. Copyright law.Unauthorized reproduction is prohibited. (Millenium Pharmaceuticals, Inc.; Cambridge, MA), for use as a single agent for the treatment of patients with multiple myeloma after two prior therapies and progressing on their most recent therapy. In 1998, Millennium Pharmaceuticals, Inc., submitted an Investigational New Drug Application for bortezomib and in January, 2003, a New Drug Application (NDA) was filed. At the time of the NDA submission, melphalan, cyclophosphamide, and carmustine had been FDA approved for myeloma treatment, and pamidronate and zoledronate were approved for reducing skeletal-related events. This commentary reports on the supporting data, the review process, and the standards of evidence employed in the approval of bortezomib.

Elderly were under-represented in the registration trials of new cancer therapies. Various strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in the elderly population.

No abstract

Gefitinib is often referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor. Studies demonstrate, however, that gefitinib inhibits the activity of other intracellular transmembrane tyrosine-specific protein kinases at concentrations similar to those at which it inhibits the epidermal growth factor signal. Maximum plasma concentrations resulting from clinically relevant doses are 0.5-1 M or more, well within the IC 50 values of several tyrosine kinases. No clinical studies have been performed that demonstrate a correlation between epidermal growth factor receptor expression and response to gefitinib. Gefitinib is 60% available after oral administration and is widely distributed throughout the body. Gefitinib is extensively metabolized in the liver by cytochrome P450 3A4 enzyme. Over a 10-day period, approximately 86% of an orally administered radioactive dose is recovered in the feces, with <4% of the dose in the urine. After daily oral administration, steady-state plasma levels are reached in 10 days and are 2-fold higher than those achieved after single doses. Gefitinib effectiveness was demonstrated in a randomized, double-blind, Phase II, multicenter trial comparing two oral doses of gefitinib (250 versus 500 mg/day). A total of 216 patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving 250 mg/day gefitinib and in 8% (6 of 76) of patients receiving 500 mg/day gefitinib. The overall objective response rate (RR) for both doses combined was 10.6% (15 of 142 patients; 95% confidence interval, 6.0 -16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range, 4.6 -18.6؉ months). Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV non-small cell lung cancer patients. Patients were randomized to receive gefitinib (250 or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n ‫؍‬ 1093) or carboplatin plus paclitaxel (n ‫؍‬ 1037). Results from this study showed no benefit (RR, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Interstitial lung disease has been observed in patients receiving gefitinib. Worldwide, the incidence of interstitial lung disease was about 1% (2% in the Japanese postmarketing experience and about 0.3% in a United States expanded access program). Approximately one-third of the cases have been fatal. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point, RR. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in diseaserelated symptoms or incr...