Author: RR

Detection of HPV DNA in the Oral Cavity Increases the Risk of Head and Neck Cancer

RR

SUMMARY: The American Cancer Society estimates that 61,760 people will be diagnosed with Head and Neck cancer in 2016 and 13,190 patients will die of the disease. Over 90% of these malignancies are Squamous Cell Carcinomas (SCCs). Oropharyngeal Squamous Cell Carcinomas (OPSCC) involve the tonsils and base of the tongue and recent studies have shown that over 70% of these tumors are caused by Human Papilloma Virus (HPV) and HPV-16 is the predominant type present in the tumor cells. The CDC estimates that more than 2,370 new cases of Human Papilloma Virus associated Oropharyngeal Squamous Cell Carcinomas (OPSCC) are diagnosed in women and nearly 9,356 are diagnosed in men, each year in the United States and this incidence has been on the rise. The malignant behavior of these tumors is dependent on the expression of viral E6 and E7 oncoproteins that inactivate the tumor suppressor proteins p53 and the retinoblastoma protein (pRb), respectively. HPV-positive OroPharyngeal Squamous Cell Carcinoma is more common among never smokers or light smokers and patients tend to be younger with better performance status.

The authors conducted this prospective study to examine the temporal association between HPV DNA detection of alpha, beta and gamma Human Papilloma Virus (HPV) types in the oral samples and risk of Head and Neck Squamous Cell Carcinoma (HNSCC). A nested case-control study was carried out among 96,650 participants, cancer free at baseline, who provided mouthwash samples in 2 large prospective cohorts: the American Cancer Society Cancer Prevention Study II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Molecular Detection of DNA from alpha, beta and gamma HPV types in mouthwash samples was performed by next-generation sequencing method. Associations between oral HPV infection and Head and Neck Squamous Cell Carcinoma (HNSCC) were adjusted for smoking status, pack-years and number of alcoholic drinks per week, which are all known and established risk factors for HNSCC.

During an average follow up of 3.9 years in both cohorts, 132 cases of HNSCC were identified which included cancers of the Oropharynx, Oral cavity and Larynx. The authors after analyzing the 132 cases of HNSCC and 396 controls nested within 2 prospective cohorts, found that detection of oral HPV-16 DNA was associated with a 22.4 fold increased risk of incident Oropharyngeal Cancer. Detection of oral beta1-HPV-5 type and gamma11-HPV and gamma12-HPV species was associated with a 3.3 to 5.5 fold higher risk of HNSCC.

The authors concluded that HPV-16 detection in the oral cavity precedes the incidence of Oropharyngeal Squamous Cell Carcinoma and this is the first study to demonstrate a temporal association between HPV DNA detection in mouthwash specimens and risk of HNSCC. Further, other HPVs including beta and gamma species may also play a role in the etiology of HNSCC. Detection of HPV DNA in the oral cavity may have important implications for its use in Oropharygeal cancer screening program. Associations of Oral α-, β-, and γ-Human Papillomavirus Types with Risk of Incident Head and Neck Cancer. Agalliu I, Gapstur S, Chen Z, et al. JAMA Oncol. 2016;2:599-606

XARELTO® Safe and Effective for Cancer Patients with Venous ThromboEmbolism

RR

SUMMARY: The Center for Disease Control and Prevention (CDC) estimates that approximately 1-2 per 1000 individuals develop Deep Vein Thrombosis/Pulmonary Embolism (PE) each year in the United States, resulting in 60,000-100,000 deaths. Venous ThromboEmbolism (VTE) is the third leading cause of cardiovascular mortality. Patients with unprovoked DVT and PE are two to four times more likely to be diagnosed with cancer within the ensuing 12 months compared to the general population. Approximately 20% of VTE events are related to underlying malignancy and patients with active malignancy have a five to six fold increased risk of VTE. In patients with cancer associated thrombosis, COUMADIN® (Warfarin) and XARELTO® (Rivaroxaban) are often prescribed, despite guidelines recommending Low Molecular Weight Heparin (LMWH) in this patient population. However, patients are less inclined to take LMWH as this is parenteral, expensive, inconvenient and carries the risk of Heparin-Induced Thrombocytopenia. Further, most patients with malignancy require indefinite anticoagulation and the safety and efficacy of LMWH in this setting is unknown. The efficacy and safety of oral, direct Factor Xa inhibitor such as XARELTO® is not well established in patients with VTE and active malignancy.

The authors in this study evaluated the risk and benefits of XARELTO® in this high-risk group of patients. In this case cohort study, the Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry included patients diagnosed with Deep Vein Thrombosis or Pulmonary Embolism, who were seen and treated with XARELTO® at the Thrombophilia Clinic, Gonda Vascular Center and Mayo Clinic in Rochester, Minn. These units work together and provide streamlined standardized care. Immediate anticoagulation therapy was provided for appropriate patients. Patients with symptomatic PE or extensive symptomatic iliofemoral Deep Vein Thrombosis were hospitalized. All patients with PE also had lower extremity duplex ultrasound to determine the source of embolism. Evaluation included upper extremity venous assessment, if a patient had symptoms suggestive of venous thrombosis or if a Central Venous Catheter was present.

Patients with acute VTE or asymptomatic PE suitable for outpatient anticoagulation therapy were counseled about the pros and cons of each anticoagulant currently approved by the FDA. Additionally, patients with active malignancy and VTE were counseled about the preferred first line of treatment with Low Molecular Weight Heparin, as well as the limited data for XARELTO® in cancer-associated VTE. Patients opting for XARELTO®, were started on treatment within the ensuing hour. Patients were evaluated every 3 months for efficacy and safety and followed prospectively from March 2013 and April 2015. The primary efficacy outcome was symptomatic venous or arterial thromboembolism occurring during the follow up period. The primary safety end point was major bleeding defined as overt bleeding plus a hemoglobin decrease of 2 or more grams/dL after the incident, transfusion of 2 or more units of packed red blood cells, or intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or fatal bleeding.

Two hundred and ninety six (N=296) of the 404 patients in the registry with Venous ThromboEmbolism (VTE), received XARELTO® and had at least 3 months of follow up. Of these 296 patients on XARELTO®, 118 patients (40%) had active malignancy and 178 patients had no cancer. The 3 most common cancer locations were Genitourinary (23.6%), Gastrointestinal (20.3%) and Lung (13.5%). It was noted that there was no significant difference in VTE recurrence between the malignant (3.3%) and the nonmalignant (2.8%) VTE groups (P=0.533). Slightly higher rates for major bleeding (P=0.06) and non major clinically relevant bleeding (P=0.08) were noted in patients with cancer, but this was not statistically significant.

The authors concluded that the efficacy and safety of XARELTO® is similar for VTE patients with and without active malignancy. Efficacy and Safety of Rivaroxaban in Patients with Venous Thromboembolism and Active Malignancy: A Single-Center Registry. Bott-Kitslaar DM, Saadiq RA, McBane RD, et al. Am J Med. 2016; 129: 615-619

Cobas EGFR Mutation Test v2

RR

The FDA on June 1, 2016 approved cobas EGFR Mutation Test v2, using plasma specimens, as a companion diagnostic test for the detection of exon 19 deletions or exon 21 (L858R) substitution mutations in the Epidermal Growth Factor Receptor (EGFR) gene, to identify patients with metastatic Non Small Cell Lung Cancer (NSCLC) eligible for treatment with TARCEVA® (Erlotinib). Cobas EGFR Mutation Test v2 is a product of Roche Molecular Systems, Inc.

TECENTRIQ® (Atezolizumab)

RR

The FDA on May 18, 2016 granted accelerated approval to TECENTRIQ® injection for the treatment of patients with locally advanced or metastatic Urothelial carcinoma, who have disease progression during or following Platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with Platinum-containing chemotherapy. TECENTRIQ® is a Programmed Death-ligand 1 (PD-L1) blocking antibody and is a product of Genentech, Inc.

OPDIVO® (Nivolumab)

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The FDA on May 17, 2016 granted accelerated approval to OPDIVO® for the treatment of patients with classical Hodgkin Lymphoma (cHL) that has relapsed or progressed after autologous Hematopoietic Stem Cell Transplantation (HSCT) and post-transplantation ADCETRIS® (Brentuximab vedotin). OPDIVO® is marketed by Bristol-Myers Squibb company

LENVIMA® (Lenvatinib)

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The FDA on May 13, 2016 approved LENVIMA® capsules in combination with AFINITOR® (Everolimus), for the treatment of advanced Renal Cell Carcinoma following one prior anti-angiogenic therapy. LENVIMA® was first approved in 2015 for the treatment of locally recurrent or metastatic, progressive, RadioActive Iodine-refractory Differentiated Thyroid Cancer. LENVIMA® is a product of Eisai, Inc.

VENCLEXTA® (Venetoclax)

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The FDA on April 11, 2016 approved VENCLEXTA® for the treatment of patients with Chronic Lymphocytic Leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. VENCLEXTA® tablets are marketed by AbbVie, Inc. and Genentech USA, Inc.

DEFITELIO® (Defibrotide Sodium)

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The FDA on March 30, 2016 approved DEFITELIO® for the treatment of adult and pediatric patients with hepatic Veno-Occlusive Disease (VOD), also known as sinusoidal obstructive syndrome, with renal or pulmonary dysfunction, following Hematopoietic Stem Cell Transplantation (HSCT). DEFITELIO® is a product of Jazz Pharmaceuticals, Inc.

XALKORI® (Crizotinib)

RR

The FDA on March 11, 2016 approved XALKORI® capsules for the treatment of patients with metastatic Non Small Cell Lung Cancer (NSCLC) whose tumors are ROS1-positive. XALKORI® is a product of Pfizer, Inc.