Scientific Director’s Office
Scientific Director’s Office
Unit of International Cooperation in Clinical Trials Aaron GOLDHIRSCH & Marco COLLEONI
Activities 2012. The main international
cooperation of the IEO in a leadership position was held within the International Breast Cancer Study Group. During 2012 the IBCSG was significantly involved in conducting research and in the presentation of results from clinical trials??? in international conferences. Presentations were conducted based on the following study designs: BIG 1-98 (1, 2), HERA (3, 4, 5), IBCSG VIII and IX (6, 7), IBCSG SOFT and TEXT (8). IBCSG Trial 23-01 (examining the need for axillary dissection in the presence of micrometastases in sentinel nodes) closed accrual in February 2010 with 6681 registered and 934 patients randomized. First results were presented at the SABCS in December 2011 and a manuscript has been submitted. IBCSG Trial 36-07 (BIG 2-06: ALTTO testing adjuvant trastuzumab and lapatinib in HER2-positive breast cancer) ended accrual with 8381 patients. Based on results from the parallel neo-adjuvant trial Neo-ALTTO, patients included in this trial who were assigned to lapatinib alone as anti-HER2 therapy were offered crossover to trastuzumab. IBCSG Trial 39-11 (Aphinity) was designed for 3806 patients and compares trastuzumab + pertuzumab to trastuzumab + placebo. Aphinity was the only large trial started within the Group in 2012. IBCSG SOFT and TEXT trials (in premenopausal women with endocrine responsive disease) completed accrual with 3066 (31 January 2011) and 2672 (11 March 2011) patients, respectively. IBCSG Co-SOFT (on cognitive function) accrued 84 and IBCSG SOFT-EST (on estrogen level profiles) 123 patients, respectively. IBCSG Trials 22-00 (CM metronomic therapy as adjuvant) and 35-07 (SOLE: extended letrozole adjuvant therapy after year 5 of adjuvant endocrine therapy for node-positive disease in postmenopausal women) terminated accrual in 2012 with more than the target of 1080 patients and a total of 4884 patients, respectively.
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IEO — Scientific Report 2012 — Ongoing Research 2013
New IBCSG Trials The closure of the SOLE and 22-00 trials leaves the Group with the planning of two small trials, SNAP and TREND. These will accrue patients in 2013. These trials represent successful collaborations with Celgene (for the use of abraxane) and Ferring (for the use of degarelix), respectively. The hope is that these promising agents will become desirable for larger adjuvant trials, and that collaborations will continue. TREND is a neo-adjuvant trial that compares degarelix (a LHRH antagonist) to triptorelin (a LHRH agonist) for premenopausal women with endocrine responsive disease. Another trial, SNAP, evaluates three schedules of nab-paclitaxel for women with advanced breast cancer. Translational Research Gene expression profiling: Collaborative investigations are underway with validations of targeted and exploration of whole-genome gene expression profiles. • RNA extracted from FFPE tumor blocks, using a mutually-agreed upon protocol, was distributed to collaborators, DNA was extracted and distributed, and additional TMAs were prepared from newly-received blocks. • Using IBCSG IX data (Tam vs. CMF+Tam), collaborators thought to determine if a proliferation score could identify a subset of women who benefit differently from the addition of chemotherapy compared to that of Tam. • Genomic Grade (GG): tumor material from BIG 1-98 patients was evaluated for a genomic grade (qRT-PCR GG) to predict distant recurrence. • Our collaborators conducted whole-genome transcript profiling of BIG 1-98 tissue, in order to identify prognostic drivers of ER+ disease, and subsequently used 2 published data sets profiled on a different platform to validate these.
References Metzger O, Giobbie-Hurder A, Mallon E, Viale G, Winer E, Thürlimann B, Gelber RD, Colleoni M, Ejlertsen B, Bonnefoi H, Coates AS, Goldhirsch A, Gusterson B. BIG 1-98 Collaborative Group, International Breast Cancer Study Group. Relative effectiveness of letrozole compared with tamoxifen for patients with lobular carcinoma in the BIG 1-98 Trial. Cancer Res 72 (24 Suppl.): 89s (Abstract S1-1), 2012 Sotiriou C, Ignatiadis M, Desmedt C, Azim Jr. HA, Veys I, Larsimont D, Lyng M, Viale G, Leyland-Jones B, Ditzel H, Giobbie-Hurder A, Regan, M, Piccart M, Michiels S. Independent validation of Genomic Grade in the BIG 1-98 study. Cancer Res 72 (24 Suppl.): 101s (Abstract S4-4), 2012 Goldhirsch A, Piccart M, Procter M, De Azambuja E, Weber H, Untch M, Smith IE, Gianni L, Jackisch C, Cameron D, Bell R, Dowsett M, Gelber RD, LeylandJones B, Baselga J. HERA trial: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow-up. Ann Oncol 23 (Suppl. 9) (Abstract 6-LBA), 2012 http://annonc.oxfordjournals.org/content/23/suppl_9/ixe1. abstract?sid=e548a8f4-adc7-4369-a2ab-6207f504f7c0 Goldhirsch A, Piccart-Gebhart MJ, Procter M, de Azambuja E, Weber HA, Untch M, Smith I, Gianni L, Jackisch C, Cameron D, Bell R, Dowsett M, Gelber RD, Leyland-Jones B, Baselga J, On Behalf of the HERA Study Team. HERA TRIAL: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2positive early breast cancer at 8 years of median follow up. Cancer Res 72 (24 Suppl.): 103s (Abstract S5-2), 2012
trastuzumab for breast cancer: coping with success. Cancer Res 72 (24 Suppl.): 465s (Abstract P5-18-02), 2012 Millar EKA, Coates AS, O’Toole SA, Selinger C, Musgrove EA, Yan M, Viale G, Regan M, Price KN, Castiglione-Gertsch M, Colleoni M, Gelber RD, Goldhirsch A, Sutherland RL. Intrinsic subtype and its clinical significance in early node negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy. Abstract #504. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting Sninsky J, Wang A, Gray K, Lagier R, Christopherson C, Rowland C, Chang M, Kammler R, Viale G, Kwok S, Regan M, Leyland-Jones B. Predictive value of a proliferation score (MS) in postmenopausal women with endocrineresponsive breast cancer: results from International Breast Cancer Study Group (IBCSG) Trial IX. Cancer Res 72 (24 Suppl.): 144s (Abstract PD10-03), 2012 Dellapasqua S, Bagnardi V, Regan MM, Rotmensz N, Mastropasqua MG, Viale G, Maiorano E, Price KN, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Colleoni M. A risk score based on histopathological features predicts higher risk of distant recurrence in premenopausal patients with lymph node-negative endocrine-responsive breast cancer. Breast 21: 621-628, 2012 (IBCSG Trial VIII) (Journal impact factor 2.491).
Regan MM, Dafni U, Karlis D, Goldhirsch A, Untch M, Smith I, Gianni L, Jackisch C, de Azambuja E, Heinzmann D, Cameron D, Bell R, Dowsett M, Baselga J, Leyland-Jones B, Piccart-Gebhart MJ, Gelber RD, on behalf of the HERA study team. Selective crossover in randomized trials of adjuvant
IEO — Scientific Report 2012 — Ongoing Research 2013
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