Phase III trials presented at ESMO 2014 report major advances in supportive care for cancer patients

Lugano/Madrid, 27 September 2014 --Phase III trials presented at the ESMO 2014 Congress report major advances in supportive care for cancer patients. Therapies have been shown to reduce chemotherapy-induced nausea and vomiting, bleeding in patients with venous thromboembolism (VTE) and cancer anorexia-cachexia syndrome (CACS).

Rolapitant was found to reduce nausea and vomiting in patients receiving cisplatin-based chemotherapy in a phase III trial. Such symptoms are often experience by patients on cisplatin and can cause dose reductions and treatment discontinuation.

The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours post-chemotherapy) compared to 58.4% of those receiving placebo (p<0.001).

ESMO spokesperson Dr Roberto Labianca, director of the Cancer Center, Ospedale Giovanni XXIII, Bergamo, Italy, said: “In this well conducted large-scale clinical trial there was a clear advantage in patients receiving rolapitant when treated with highly emetogenic chemotherapy. It is remarkable that this effect was observed worldwide across different geographic regions. As the new drug is very selective and long-acting, and also well tolerated, it could be easily introduced in clinical practice in order to prevent both acute and delayed chemotherapy-induced nausea and vomiting.”

Oral rivaroxaban reduced the risk of bleeding in patients with cancer and acute VTE who participated in the EINSTEIN DVT and EINSTEIN PE phase III trials. Both studies compared rivaroxaban to standard treatment with enoxaparin/vitamin K antagonist (VKA) for the treatment of symptomatic VTE in patients with cancer. Anticoagulant therapy is indicated to prevent recurrent VTE but is associated with a high risk of major bleeding.

The study found that the incidence of recurrent VTE and of mortality was similar between the rivaroxaban and enoxaparin/VKA groups for patients with active cancer and a history of cancer. The risk of major bleeding significantly reduced with rivaroxaban in patients with active cancer, with a hazard ratio of 0.42 but was similar between treatments for patients with a history of cancer.

Labianca said: “Rivaroxaban is an oral drug, with the same antithrombotic effect as compared to the traditional drugs, but with a reduced risk of bleeding. This characteristic can be very important in clinical practice, allowing an easier and more convenient treatment of such a serious complication of cancer.”

The phase III ROMANA 1 trial investigated the efficacy and safety of anamorelin HCI, a novel, selective ghrelin receptor agonist, for the treatment of CACS in patients with unresectabe advanced non-small cell lung cancer.

Dr Labianca said: “This is really an important advance, as the study emphasises the absolute need of establishing an approach of simultaneous palliative care in patients with advanced disease (such as NSCLC) treated with antitumour drugs and affected with serious symptoms like CACS.”

He concluded: “These studies demonstrate the research efforts directed toward improving the quality of life for patients with cancer and the significant advances that have been made to control some of the most severe repercussions of treatment.”


Notes to Editors

LBA47: Phase 3 (P04832) trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy

LBA48: Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism in patients with cancer

1483O_PR: Anamorelin for the treatment of cancer anorexia-cachexia in patients with advanced NSCLC: results from the pivotal phase III study ROMANA 1and 2

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Abstract: LBA47_PR

Phase 3 (P04832) trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy

M.R. Chasen1, A. Poma2, M.L. Hedley3, R. Martell2, C. Gridelli4
1Dept Palliative Rehabilitation, Elizabeth Bruyere HospitalDivision of Palliative Care, Ottawa, AB, CANADA, 2Medical, TESARO, Waltham, MA, USA, 3TESARO Inc., Waltham, MA, USA, 4Medical Oncology, UO Oncologia Medica"S.G. Moscati Hospital", Avellino, ITALY

Aim:Rolapitant is a highly selective competitive long acting NK-1 receptor antagonist that demonstrated safety and prevention of CINV in both phase 2 and 3 trials.

Methods:A multi-center, randomized double-blind phase 3 trial was conducted in patients (pts) receiving cisplatin-based chemotherapy. 532 pts were randomized 1:1 to receive oral rolapitant + granisetron/dexamethasone (G/D) or placebo + G/D prior to chemotherapy. The primary endpoint was complete response (CR; no emesis/no rescue meds) in the delayed phase (>24-120 hrs) post-chemotherapy. Key secondary endpoints included CR during acute (0-24 hrs) and overall (0-120 hrs) phases. Treatment comparisons were performed using a Mantel-Haenszel chi-square test; to control for type 1 error, testing was conducted in a stepwise fashion for key secondary endpoints. A regional CR analysis was prospectively conducted on North America (NA), Asia/South Africa (ASA), Europe (E), and Central/South America (CSA). Daily quality of life (QoL) was assessed via Functional Living Index-Emesis Questionnaire.

Results:Demographics were well balanced with a mdn age of 57.3y (range 20-90). The primary objective of this study was achieved with a higher CR rate in the delayed phase compared to placebo (72.7% vs 58.4%, p < 0.001). Statically significant results were also observed in key secondary endpoints of acute phase CR rate (83.7% vs 73.7%, p = 0.005), and overall CR rate (70.1% vs 56.5%, p =0.001). Slightly more pts reported no impact on daily QoL with rolapitant (72.8% vs 67.8%, p = 0.231). Addition of rolapitant conferred a CR improvement across geographic regions in both the delayed and acute phases (table). Treatment emergent AEs were consistent across both arms, and generally related to underlying medical condition or chemotherapy.

Conclusions:Rolapitant + G/D was well tolerated and superior to G/D alone in preventing CINV in pts receiving cisplatin-based therapies, and this effect was observed across geographic regions.

Disclosure:A. Poma, M.L. Hedley and R. Martell: is an employee of TESARO, the sponsor of this abstract. All other authors have declared no conflicts of interest.

Keywords:highly emetogenic chemotherapy, rolapitant, NK-1 receptor antagonist, chemotherapy-induced nausea and vomiting

Abstract LBA48

Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism in patients with cancer

M.H. Prins1, T. Lensing2, P. Prandoni3, A.T. Cohen4, B. Davidson5, F. Misselwitz2, Á. Pap2, M. Trajanovic6, S. Berkowitz6, P. Wells7
1Medical Center, Maastricht University Medical Center, Maastricht, NETHERLANDS, 2Bayer HealthCare AG, Wuppertal, GERMANY, 3Department of Cardiothoracic and Vascular Sciences, University Hospital of Padua, Padua, ITALY, 4Department of Haematological Medicine, King’s College Hospital, London, UK, 5University of Washington School of Medicine, Seattle, WA, USA, 6Bayer Healthcare Pharmaceuticals, Whippany, NJ, USA, 7Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, CANADA

Objective:To compare the efficacy and safety of oral rivaroxaban with that of enoxaparin/vitamin K antagonist (VKA) in patients with cancer among 8282 patients with acute venous thromboembolism (VTE) enrolled in the EINSTEIN programme.

Rationale:Patients with cancer and VTE constitute a medical challenge for physicians because anticoagulant treatment is indicated to prevent recurrent VTE but is associated with a high risk of major bleeding.

Methods:EINSTEIN DVT and EINSTEIN PE were randomized, event-driven, non-inferiority, open-label phase III studies. Patients were treated for 3, 6 or 12 months with rivaroxaban (15 mg twice daily for 21 days followed by 20 mg once daily) or enoxaparin/VKA (international normalized ratio 2.03.0) and followed for suspected recurrent VTE, bleeding and mortality. Cancer patients were classified as: active cancer at baseline (diagnosis or treatment within 6 months before enrolment or recurrent/metastatic cancer) or diagnosed during the study (n=655); or a history of cancer (n=469).

Results:Recurrent VTE occurred with a similar incidence in the rivaroxaban and enoxaparin/VKA groups in patients with active cancer (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.351.30) and patients with a history of cancer (HR 0.98; 95% CI 0.283.43). In patients with active cancer, the risk of major bleeding was significantly reduced in the rivaroxaban group (HR 0.42; 95% CI 0.180.99), whereas it was similar between treatments in patients with a history of cancer (HR 0.23; 95% CI 0.032.06). Mortality occurred with a similar incidence between treatments in patients with active cancer (HR 0.93; 95% CI 0.641.35) and patients with a history of cancer (HR 1.12; 95% CI 0.304.22).

Conclusions:Rivaroxaban had similar efficacy to enoxaparin/VKA in patients with VTE and active cancer or a history of cancer, but was associated with a significant reduction in major bleeding in patients with active cancer.

Disclosure:M.H. Prins: is a consultant advisor for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Pfizer, Sanofi, Boehringer Ingelheim, GlaxoSmithKline (GSK), LEO, and ThromboGenics; T. Lensing, F. Misselwitz, Á.F. Pap, M. Trajanovic and S.D. Berkowitz: is an employee of Bayer HealthCare Pharmaceuticals; P. Prandoni: has received consultant fees from Bayer Pharma, Daiichi Sankyo, Pfizer, Boehringer-Ingelheim and Sanofi-Aventis; A.T. Cohen: has received consultancy and clinical trial funding from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Daiichi, GSK, Johnson & Johnson, Mitsubishi Pharma, Pfizer, Portola, Sanofi-aventis, Schering-Plough & Takeda; B.L. Davidson: has received travel support from Bayer Healthcare, and is a steering committee member for Bayer HealthCare and Daiichi Sankyo;P. Wells: has received research support from Bristol-Myers Squibb, Pfizer; has participated on scientific advisory boards for Bayer Schering Pharma, Pfizer & Boehringer Ingelheim; and has received honoraria from Bayer Schering Pharma, Pfizer & Biomerieux.

Keywords:rivaroxaban, anticoagulants, venous thromboembolism, cancer

Abstract 1483O

Anamorelin for the treatment of cancer anorexia-cachexia in NSCLC: results from the Phase 3 studies ROMANA 1 and 2

J. Temel1, D. Currow2, K. Fearon3, L. Gleich4, Y. Yan5, J. Friend5, A. Abernethy6
1Department of Medicine, Massachusetts General Hospital, Boston, MA, USA, 2Palliative and Supportive Services, Flinders University, Adelaide, SA, AUSTRALIA, 3Surgical Oncology, Western General Hospital, Edinburgh, UK, 4Medical Affairs, Medpace, Cincinnati, OH, USA, 5R&D, Helsinn Therapeutics, Inc., Bridgewater, NJ, USA, 6School of Medicine, Duke University, Durham, NC, USA

Background:Cancer anorexia-cachexia syndrome is a common debilitating condition, characterized by decreased body weight, mainly lean body mass (LBM) and negatively impacts quality of life and prognosis. Anamorelin HCl (ANAM) is a novel selective ghrelin receptor agonist with appetite-enhancing and anabolic activity.

Methods:These were two international, double-blind, Phase 3 trials assessing ANAM efficacy and safety in patients with unresectable Stage III/IV NSCLC, ECOG 0-2 and cachexia (≥5% weight loss within prior 6 months or BMI <20 kg/m2). Patients were randomized (2:1) to 100 mg ANAM or placebo, given daily orally for 12 weeks and were permitted to receive chemotherapy while on study.Co-primary endpoints were change from baseline over 12 weeks in LBM (measured by DXA) and in handgrip strength (HGS). Secondary endpoints included change in body weight and in the anorexia-cachexia subdomain of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire. Safety assessments included lab values and adverse events (AEs).

Results: There were no within-study population differences for ROMANA 1 (N=484) and ROMANA 2 (N=495). Over 12 weeks, ANAM significantly increased LBM vs placebo (p<0.0001) in both studies. In ROMANA 1, median change in LBM was 1.10 kg [95% CI 0.76; 1.42] for ANAM vs -0.44 kg [95% CI -0.88; 0.20] for placebo; similarly, changes in ROMANA 2 were ANAM 0.75 kg (95% CI 0.51; 1.00) vs placebo -0.96 kg (95% CI -1.27; -0.46). Change in HGS was not statistically different between study arms. ANAM increased body weight (2.200.3 vs 0.140.4 kg; p<0.0001; and 0.950.4 vs -0.570.4 kg; p<0.0001) and improved FAACT subdomain scores (4.120.8 vs 1.920.8; p=0.0004; and 3.480.9 vs 1.341.0; p=0.0016). In the ANAM arm, most frequent drug-related AEs were hyperglycemia (5.3%) and nausea (3.8%) for ROMANA 1, hyperglycemia (4.2%) and diabetes (2.1%) for ROMANA 2. Both studies had few drug-related Grade ≥3 AEs (0.9%, 2.7%).

Conclusions: In two global, large-scale Phase 3 studies, ANAM for 12 weeks was well tolerated, and significantly improved LBM, body weight, and anorexia-cachexia symptoms/concerns in advanced NSCLC patients with cachexia.

Disclosure: K. Fearon: has received research funding from Helsinn; L. Gleich: is an employee of Medpace, Inc.
Y. Yan and J. Friend: is an employee of Helsinn Therapeutics (US), Inc.; A. Abernethy: Received research funding from DARA, Celgene, Helsinn, Bristol-Myers Squibb (BMS), Dendreon, GSK, Pfizer; has consulting agreements with BMS and ACORN Research; is on the Board of Directors of athenahealth (a health information technology company).All other authors have declared no conflicts of interest.

Keywords: cachexia, anamorelin, ghrelin, Phase III