|Canadian Cancer Trials Group MA.31 - A Randomized, Open-Label, Phase III Study of Taxane-Based Chemotherapy with Lapatinib or Trastuzumab as First-Line Therapy for Women with HER2/neu Positive Metastatic Breast Cancer
The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of HER2-positive metastatic breast cancer is unknown.
Canadian Cancer Trials Group MA.31 compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary endpoint was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumours. The primary test statistic was a stratified log-rank test for non-inferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumours.
In total, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. The results of the trial showed that as first-line therapy for HER2-positive metastatic breast cancer, lapatinib combined with taxane, was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane.
Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2 - Positive Advanced Breast Cancer: Final Results of Canadian Cancer Trials Group MA.31 (ONLINE). J Clin Oncol 2015.
Canadian Cancer Trials Group SC.20U - A Phase III Study of the Effect of Re-irradiation for Bone Pain on Urinary Markers of Osteoclast Activity
Chow E, DeAngelis C, Chen BE, Azad A, Meyer RM, Wilson C, Kerba M, Bezjak A, Wilson P, Nabid A, Greenland J, Rees G, Vieth R, Wong RKS, Hoskin P. Effect of re-irradiation for painful bone metastases on urinary markers of osteoclast activity (Canadian Cancer Trials Group SC.20U) (ONLINE). Radiotherapy and Oncology 2015.
The Canadian Cancer Trials Group SC.20 randomized trial confirmed the effectiveness of re-irradiation to painful bone metastases. This companion study correlates urinary markers of osteoclast activity with response to re-irradiation, survival and skeletal related events (SREs).
Pain response was assessed using the International Consensus Endpoints. Urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1 month after re-irradiation were correlated to response to re-irradiation and then to both, either or none of the initial and re-irradiation: frequent responders (response to both); eventual responders (response to re-irradiation only); eventual non-responders (response to initial radiation only), and absolute non-responders (no response to both).
The investigators found there were significant differences between responders and non-responders to re-irradiation for PYD and DPD at baseline. The urinary markers in the absolute non-responders were markedly elevated at both baseline and follow-up with a statistically significant difference for DPD at baseline.
Canadian Cancer Trials Group CO.17 - A Phase III Randomized Study of Cetuximab (Erbitux TM, C225) and Best Supportive Care versus Best Supportive Care in Patients with Pretreated Metastatic Epiderma Jonker DJ, Karapetis CS, O'Callaghan CJ, Moore MJ, Wong R, Tebbutt NC, Underhill C, Yip D, Zalcberg JR, Tu D, Goodwin RA. Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17 (ONLINE). Eur J Can 2015.
Canadian Cancer Trials Group HD.7 (ECOG E2496) - A Randomized Phase III Trial of ABVD Versus Stanford V with or without Radiation Therapy in Locally Extensive and Advanced Stage Hodgkin's Disease
Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Stewart DA, Gordon LI, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial (ONLINE). J Clin Oncol 2015.
Canadian Cancer Trials Group LY.12 - A Phase III Study of Gemcitabine, Dexamethasone, and Cisplatin Compared to Dexamethasone, Cytarabine, and Cisplatin Plus/Minus Rituximab [(R) -GDP VS (R) -DHAP] as Salvage Chemotherapy for Patients with Relapsed or Refractory Aggressive Histology Non-Hodgkin's Lymphoma Prior to Autologous Stem Cell Transplant and Followed by Maintenance Rituximab Versus Observation
Cheung MC, Hay AE, Crump M, Imrie KR, Song Y, Hassan S, Risebrough N, Sussman J, Couban S, MacDonald D, Kukreti V, Kouroukis CT, Baetz T, Szwajcer D, Desjardins P, Shepherd L, Meyer RM, Le A, Chen BE, Mittmann N, for the Committee on Economic Analysis and the Hematology Disease Site Committee NCTG. Gemcitabine/Dexamethasone/Cisplatin vs Cytarabine/Dexamethasone/Cisplatin for Relapsed or Refractory Aggressive-Histology Lymphoma: Cost-Utility Analysis of Canadian Cancer Trials Group LY.12 (ONLINE). J Natl Cancer Inst 107: 2015.
Canadian Cancer Trials Group MA.21 - A Phase III Adjuvant Trial of Sequenced EC + Filgrastim + Epoetin Alfa Followed by Paclitaxel Versus Sequenced AC Followed by Paclitaxel Versus CEF as Therapy for Premenopausal Women and Early Postmenopausal Women Who Have Had Potentially Curative Surgery for Node Positive or High Risk
Lohmann A, Chapman JA, Burnell M, Levine M, Tsvetkova E, Pritchard K, Gelmon K, O'Brien P, Han L, Rugo H, Albain K, Perez E, Vandenberg T, Chalchal H, Sawhney R, Shepherd L, Goodwin P. Prognostic associations of 25 hydroxy vitamin D in Canadian Cancer Trials Group MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer. Breast Cancer Res Treat 150: 605-11, 2015.
Canadian Cancer Trials Group BR.10 - A Phase III Prospective Randomized Study of Adjuvant Chemotherapy with Vinorelbine and Cisplatin in Completely Resected Non-Small Cell Lung Cancer with Companion Tumour Marker Evaluation
Tsao MS, Marguet S, Le Teuff G, Lantuejoul S, Shepherd FA, Seymour L, Kratzke R, Graziano SL, Popper HH, Rosell R, Douillard JY, Le-Chevalier T, Pignon JP, Soria JC, Brambilla EM. Subtype Classification of Lung Adenocarcinoma Predicts Benefit From Adjuvant Chemotherapy in Patients Undergoing Complete Resection (ONLINE). J Clin Oncol 2015.