The FDA on June 13, 2018 granted accelerated approval to KEYTRUDA® for the treatment of adult and pediatric patients with refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL), or who have relapsed after two or more prior lines of therapy. KEYTRUDA® is a product of Merck and Co., Inc.
Author: RR
AVASTIN® (Bevacizumab)
The FDA on June 13, 2018 approved AVASTIN® for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with Carboplatin and Paclitaxel, followed by single-agent AVASTIN®, for stage III or IV disease, after initial surgical resection. AVASTIN® is a product of Genentech, Inc.
KEYTRUDA® (Pembrolizumab)
The FDA on June 12, 2018 approved KEYTRUDA® for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, whose tumors express PD-L1 (CPS 1 or more), as determined by an FDA-approved test. KEYTRUDA® is a product of Merck and Co., Inc.
VENCLEXTA® (Venetoclax)
The FDA on June 8, 2018 granted regular approval to VENCLEXTA® for patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. VENCLEXTA® is a product of AbbVie Inc. and Genentech Inc.
MIRCERA® (Methoxy polyethylene glycol-epoetin beta)
The FDA on June 7, 2018 approved MIRCERA® for the treatment of pediatric patients 5 to 17 years of age on hemodialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA. MIRCERA® is a product of Vifor Pharma Inc.
FULPHILA® (Pegfilgrastim-jmdb)
The FDA on June 4, 2018 approved FULPHILA® as a biosimilar to NEULASTA® (Pegfilgrastim, Amgen, Inc.), to decrease the chance of infection as suggested by febrile neutropenia in patients with non-myeloid cancer, who are receiving myelosuppressive chemotherapy that has a clinically significant incidence of febrile neutropenia. FULPHILA® is a product of Mylan GmbH.
DOPTELET® (Avatrombopag)
The FDA on May 21, 2018 approved DOPTELET® for thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure. DOPTELET® is a product of AkaRx Inc.
RETACRIT® (Epoetin alfa-epbx)
The FDA on May 15, 2018 approved RETACRIT® as a biosimilar to EPOGEN®/PROCRIT® (Epoetin alfa, Amgen Inc.), for the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis, use of Zidovudine in patients with HIV infection and the effects of concomitant myelosuppressive chemotherapy. It is also approved for the reduction of allogeneic red blood cell transfusions in patients undergoing elective, noncardiac, nonvascular surgery. RETACRIT® is a product of Hospira Inc., a subsidiary of Pfizer Inc.
Late Breaking Abstract – ASCO 2018 mFOLFIRINOX Regimen Significantly Improves Overall Survival in Resected Pancreatic Cancer
SUMMARY: The American Cancer Society estimates that in 2018, about 55,440 people will be diagnosed with pancreatic cancer and about 44,330 people will die of the disease. Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States and Western Europe. Curative surgical resection has been shown to significantly improve Overall Survival (OS) when compared to Chemoradiation, for resectable Pancreatic Cancer. The standard surgical procedure for tumors of the Pancreatic head is the Pancreaticoduodenectomy (Whipple procedure), whereas distal Pancreatectomy is performed for tumors of the body or tail of the Pancreas. Previously published studies concluded that 6 months of Gemcitabine based adjuvant therapy improves Overall Survival for patients with resectable Pancreatic Cancer. FOLFIRINOX chemotherapy regimen however, is more effective than Gemcitabine as first-line treatment, in metastatic pancreatic cancer, for patients with good Performance Status. The following study was conducted to assess the benefit of mFOLFIRINOX regimen in the adjuvant setting.
PRODIGE 24/CCTG PA.6 is a phase III multicenter, randomized clinical trial in which 493 patients were enrolled. Eligible patients had histologically proven, nonmetastatic, pancreatic ductal adenocarcinomas, and had undergone R0 (curative resection) or R1(microscopic residual tumor/positive margins) resection, with no residual tumor on a postoperative CT scan. Patients had a WHO Performance Status of 1 or less and were randomized in a 1:1 ratio, 3-12 weeks after surgery, to receive Gemcitabine on days 1, 8, and 15 every 28 days for 6 cycles (Group A, N=246)) or mFOLFIRINOX regimen, which consisted of Oxaliplatin 85 mg/m², Leucovorin 400 mg/m², Irinotecan 150 mg/m² D1, and 5-FU 2400mg/m² over 46 hours, all drugs given IV, every 14 days for 12 cycles (Group B, N=247). The Primary endpoint was Disease Free Survival (DFS) and Secondary endpoints included Overall Survival (OS), Metastasis Free Survival (MFS), and Adverse Events (AE).
After a median follow up of 33.6 months, patients who received mFOLFIRINOX had a median DFS of 21.6 months compared with 12.8 months with Gemcitabine (HR=0.59; P<0.001) and the 3-year DFS was 39.7% with mFOLFIRINOX and 21.4% with Gemcitabine. The median OS was nearly 20 months longer with a mFOLFIRINOX regimen than with Gemcitabine (54.4 months versus 35 months). This represented a 34% reduction in the risk of death with mFOLFIRINOX (HR=0.66; P=0.003). The median MFS with mFOLFIRINOX regimen was 30.4 months versus 17.7 months with Gemcitabine (HR =0.59). Patients receiving mFOLFIRINOX experienced higher rates of grade 3 or 4 Adverse Events than with Gemcitabine for vomiting, diarrhea, fatigue, mucositis and sensory peripheral neuropathy. In the Gemcitabine group, the rate of grade 3/4 Adverse Events was higher for thrombocytopenia and febrile neutropenia.
It was concluded that adjuvant mFOLFIRINOX significantly improves Disease Free Survival, Metastasis Free Survival and Overall Survival, compared to Gemcitabine, after pancreatic cancer resection, in good Performance Status patients and should therefore be considered the new standard of care. It should be noted that patients with pancreatic cancer who undergo surgical resection, are fit enough to undergo this procedure and these patients would be the most likely candidates for mFOLFIRINOX. For those patients whose Performance Status is poor 12 weeks after surgery, and in those with clear contraindications to mFOLFIRINOX regimen, single agent Gemcitabine is an alternative treatment option. Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. Conroy T, Hammel P, Hebbar M, et al. J Clin Oncol 36, 2018 (suppl; abstr LBA4001)
Late Breaking Abstract – ASCO 2018 First-Line KEYTRUDA® Superior to Chemotherapy in NSCLC
SUMMARY: Lung cancer is the second most common cancer in both men and women and accounts for about 14% of all new cancers and 27% of all cancer deaths. The American Cancer Society estimates that for 2018 about 234,030 new cases of lung cancer will be diagnosed and over 154,050 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Of the three main subtypes of Non Small Cell Lung Cancer (NSCLC), 30% are Squamous Cell Carcinomas (SCC), 40% are Adenocarcinomas and 10% are Large cell carcinomas.
KEYTRUDA® (Pembrolizumab) is a fully humanized, Immunoglobulin G4, anti-PD-1, monoclonal antibody, that binds to the PD-1 receptor and blocks its interaction with ligands PD-L1 and PD-L2. It thereby reverses the PD-1 pathway-mediated inhibition of the immune response and unleashes the tumor-specific effector T cells. High level of Programmed Death-Ligand 1 (PD-L1) expression is defined as membranous PD-L1 expression on at least 50% of the tumor cells, regardless of the staining intensity. It is estimated that based on observations from previous studies, approximately 25% of the patients with advanced NSCLC have a high level of PD-L1 expression and high level of PD-L1 expression has been associated with significantly increased response rates to KEYTRUDA®. The FDA approved KEYTRUDA® for the first-line treatment of advanced NSCLC with high PD-L1 expression (Tumor Proportion Score of 50% or more), as well as in combination with Pemetrexed and Carboplatin, as first-line treatment of patients with metastatic nonsquamous NSCLC and for previously treated advanced NSCLC with a PD-L1 Tumor Proportion Score of 1% or more. Currently, KEYTRUDA® is the only FDA approved immunotherapy for initial treatment of NSCLC as monotherapy (KEYNOTE-024) or in combination with chemotherapy. In KEYNOTE-024, KEYTRUDA® significantly improved Progression Free Survival and Overall Survival compared to chemotherapy, as first-line treatment for metastatic NSCLC, without targetable mutations and PD-L1 TPS of 50% or more. KEYNOTE-042 trial evaluated the benefit of KEYTRUDA® in patients whose tumors had a much lower level of PD-L1 expression (TPS of 1% or higher).
KEYNOTE-042 is a large, international, multicenter, randomized phase III trial in which 1274 patients with untreated locally advanced or metastatic NSCLC were randomly assigned to KEYTRUDA® or chemotherapy with Paclitaxel plus Carboplatin or Pemetrexed plus Carboplatin. In this study, both squamous and non-squamous cancers with PD-L1 Tumor Proportion Score (TPS) of 1% or more were included, but tumors with sensitizing Epidermal Growth Factor Receptor (EGFR) or Anaplastic Lymphoma Kinase (ALK) mutations cancers with genetic changes, that could be treated with targeted therapies such as EGFR and ALK inhibitors, were excluded. Eligible patients were randomly assigned in a 1:1 to receive either KEYTRUDA® 200 mg IV every 3 weeks for up to 35 cycles or investigator’s choice of up to 6 cycles of chemotherapy with Paclitaxel plus Carboplatin or Pemetrexed plus Carboplatin, with optional Pemetrexed maintenance for nonsquamous NSCLC. Patients were divided into 3 treatment groups based on their PD-L1 Tumor Proportion Score (TPS): TPS 50% or more (N=599), TPS 20% or more (N=818), and TPS 1% or more (N=1274). Each PD-L1 expression group had equal numbers of patients receiving KEYTRUDA® and chemotherapy. The Primary end points were Overall Survival (OS) in patients with TPS 50% or more, 20% or more, and 1% or more.
At a median follow up of 12.8 months, 13.7% of patients were still receiving KEYTRUDA® compared with 4.9% on Pemetrexed maintenance therapy. It was noted that KEYTRUDA® was significantly superior to chemotherapy in all PD-L1 expression subsets. In patients with a PD-L1 TPS 50% or more, the median OS with KEYTRUDA® was 20 months versus 12.2 months for chemotherapy (HR=0.69, P=0.0003), for patients with PD-L1 TPS 20% or more, the median OS was 17.7 months versus 13 months respectively (HR=0.77, P=0.002), and for those with PD-L1 TPS 1% or more, the median OS was 16.7 months versus 12.1 months respectively (HR=0.81, P = 0.0018). The Response Rates (RR) were also higher among patients who received KEYTRUDA®, with RR of 39.5% for KEYTRUDA® versus 32% for chemotherapy in patients with a TPS 50% or more, 33.4% and 28.9% respectively in patients with TPS 20% or more and 27.3% and 26.5%, respectively, in patients with TPS of 1% or more. The duration of response was also superior with KEYTRUDA® in all three PD-L1 subgroups compared to chemotherapy (20.2 months versus 8-11 months). Patients receiving KEYTRUDA® experienced fewer severe Adverse Events, compared with chemotherapy (17.8% versus 41%).
The authors concluded that this is the largest clinical trial of KEYTRUDA® as a stand-alone therapy, and is the first study with a Primary end point of OS to demonstrate superiority of KEYTRUDA® over platinum-based chemotherapy, in patients with previously untreated advanced/metastatic NSCLC, without sensitizing EGFR or ALK alterations and a PD-L1 TPS of 1% or more. These data confirmed the benefit of KEYTRUDA® monotherapy as a standard first-line treatment, for PD-L1-expressing advanced/metastatic NSCLC. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study. Lopes G, Wu Y-L, Kudaba I, et al. J Clin Oncol 36, 2018 (suppl; abstr LBA4)