Annual Meeting Proceedings II - Newly Released Abstracts for
Annual Meeting Proceedings II - Newly Released Abstracts for Annual Meeting Proceedings II - Newly Released Abstracts for
GASTROINTESTINAL (COLORECTAL) CANCER LBA3501 Oral Abstract Session, Sun, 9:45 AM-12:45 PM Results of the X-PECT study: A phase III randomized double-blind, placebocontrolled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC). Johanna C. Bendell, Thomas J. Ervin, Neil N. Senzer, Donald A. Richards, Irfan Firdaus, A. Craig Lockhart, Allen Lee Cohn, Mansoor N. Saleh, Lesa R. Gardner, Peter Sportelli, Cathy Eng; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Sarah Cannon Research Institute/Florida Cancer Specialists, Englewood, FL; Mary Crowley Cancer Research Center, Dallas, TX; Texas Oncology- Tyler, Tyler, TX; Sarah Cannon Research Institute/Oncology Hematology Care, Inc, Cincinnati, OH; Washington University School of Medicine , St. Louis, MO; Rocky Mountain Cancer Center, LLP, Denver, CO; Georgia Cancer Specialists PC, Sandy Springs, GA; Keryx Biopharmaceuticals, Inc., New York, NY; University of Texas M. D. Anderson Cancer Center, Houston, TX Background: Perifosine (P) is an oral, synthetic alkylphospholipid that inhibits or modifies signal transduction pathways including AKT, NFkB and JNK. A randomized phase II study examined P-CAP vs. CAP in pts with 2nd or 3rd line mCRC. This study showed improvement in mTTP (HR 0.254 [0.117, 0.555]) and mOS (HR 0.370 [0.180,0.763]). Based on these results, a randomized phase III study of P-CAP vs. CAP with a primary endpoint of overall survival (OS) in pts with refractory mCRC was initiated. Methods: The study was a prospective, randomized, double-blind, placebo-controlled randomized phase III trial. Eligible pts had mCRC which was refractory to all standard therapies. Pts randomized 1:1 to Arm A � P-CAP (P 50 mg PO QD � CAP 1000 mg/m 2 PO BID d1-14) or Arm B � CAP (placebo � CAP 1000 mg/m2 PO BID d 1-14). Cycles were 21 days. Baseline tumor block collection and a biomarker cohort of pts with preand on-treatment tumor and blood samples were performed. Results: Between 3/31/10 and 8/12/11, 468 pts were randomized, 234 pts were in each arm. Baseline demographics were balanced between the arms: age � 65y (A: 65%, B: 58.5%), male (A: 57.7%, B: 53.0%), ECOG PS 0 (A: 39.7%, B: 39.7%), K-ras mutant (A: 50.4%, B: 51.3%), and median number of prior therapies (A: 4, B: 4). As of 3/19/12, median follow up was 6.6 months. Median overall survival: Arm A � 6.4 mo, Arm B � 6.8 mo, HR 1.111 [0.905,1.365], p � 0.315. Median overall survival for K-ras WT pts: Arm A � 6.6 mo, Arm B � 6.8 mo, HR 1.020 [0.763,1.365], p � 0.894; K-ras mutant pts: Arm A � 5.4 mo, Arm B � 6.9 mo HR 1.192 [0.890,1.596], p � 0.238. Conclusions: Despite promising randomized phase II data, this phase III study shows no benefit in overall survival adding perifosine to capecitabine in the refractory colorectal cancer setting. Response rate, progression free survival, and safety data will be presented. Biomarker analysis is pending to see if subgroups of patients may have potential benefit. © 2012 American Society of Clinical Oncology. Reprinted with permission.
GASTROINTESTINAL (COLORECTAL) CANCER CRA3503 Oral Abstract Session, Sun, 9:45 AM-12:45 PM Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: Results of a randomized phase III intergroup study (TML study). Dirk Arnold, Thierry Andre, Jaafar Bennouna, Javier Sastre, Pia J. Osterlund, Richard Greil, Eric Van Cutsem, Roger Von Moos, Irmarie Reyes-Rivera, Belguendouz Bendahmane, Stefan Kubicka; Hubertus Wald Tumor Center, University Cancer Center Hamburg (UCCH), Hamburg, Germany; Hopital Saint-Antoine, Paris, France; Institut de Cancerologie de l’Ouest/Site René Gauducheau, Nantes, France; Hospital Clínico San Carlos, Madrid, Spain; Helsinki University Central Hospital, Helsinki, Finland; IIIrd Medical Department with Hematology, Medical Oncology, Paracelsus Medical University Hospital Salzburg and AGMT (Arbeitsgemeinschaft Medikamentöse Tumortherapie), Salzburg, Austria; University Hospital Gasthuisberg, Leuven, Belgium; Kantonsspital Graubuenden, Graubuenden, Switzerland; Genentech, South San Francisco, CA; Roche, Basel, Switzerland; District Clinic Reutlingen, Department of Internal Medicine I, Reutlingen, Germany Background: BEV in combination with fluoropyrimidine-based CT is standard treatment for mCRC in the first-line (1L) and BEV-naïve second-line (2L) settings. This is the first randomized study evaluating the benefit of continuing BEV in combination with standard CT as 2L treatment for patients with mCRC who progressed after receiving a standard BEV-containing regimen in the 1L setting. Methods: Patients with unresectable, histologically confirmed mCRC who progressed within 3 months after discontinuation of 1L BEV � CT were randomised to 2L fluoropyrimidine-based CT � BEV (2.5 mg/kg/wk equivalent). Choice of oxaliplatin- or irinotecan-based 2L CT was dependent on the regimen used in 1L (crossover) and included as a stratification variable. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate and safety. Results: 820 patients were randomized from February 2006 to June 2010 (409 to BEV � CT and 411 to CT alone). Baseline patient and disease characteristics were well balanced between arms. The study met its primary endpoint; median OS was 11.2 months for BEV � CT and 9.8 months for CT (HR�0.81; 95% CI 0.69–0.94; unstratified log-rank test, p�0.0062). Median PFS was 5.7 months for BEV � CT and 4.1 months for CT (HR�0.68; 95% CI 0.59–0.78; unstratified log-rank test, p�0.0001). The response rate was 5.4% for BEV � CT and 3.9% for CT (unstratified Chi-Square Test, p�0.3113). The adverse event profile was consistent with previously reported data for BEV � CT. Compared with historical data from BEV treatment in 1L or 2L mCRC, BEV-related adverse events were not increased when continuing BEV beyond progression. Conclusions: This is the first randomized study to prospectively investigate the impact of continuing BEV treatment in 2L mCRC for patients who progressed after receiving a BEV-containing regimen in 1L. Our findings demonstrate that BEV � CT (crossed over from 1L regimen) continued beyond progression significantly prolongs OS and PFS in 2L mCRC. Additional analysis (including biomarker evaluation) is ongoing. © 2012 American Society of Clinical Oncology. Reprinted with permission.
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- Page 3 and 4: LYMPHOMA AND PLASMA CELL DISORDERS
- Page 5 and 6: BREAST CANCER—HER2/ER LBA506 Oral
- Page 7: GASTROINTESTINAL (COLORECTAL) CANCE
GASTROINTESTINAL (COLORECTAL) CANCER<br />
LBA3501 Oral Abstract Session, Sun, 9:45 AM-12:45 PM<br />
Results of the X-PECT study: A phase <strong>II</strong>I randomized double-blind, placebocontrolled<br />
study of perifosine plus capecitabine (P-CAP) versus placebo plus<br />
capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer<br />
(mCRC).<br />
Johanna C. Bendell, Thomas J. Ervin, Neil N. Senzer, Donald A. Richards, Irfan Firdaus,<br />
A. Craig Lockhart, Allen Lee Cohn, Mansoor N. Saleh, Lesa R. Gardner, Peter Sportelli, Cathy Eng; Sarah<br />
Cannon Research Institute/Tennessee Oncology, Nashville, TN; Sarah Cannon Research Institute/Florida<br />
Cancer Specialists, Englewood, FL; Mary Crowley Cancer Research Center, Dallas, TX; Texas Oncology-<br />
Tyler, Tyler, TX; Sarah Cannon Research Institute/Oncology Hematology Care, Inc, Cincinnati, OH;<br />
Washington University School of Medicine , St. Louis, MO; Rocky Mountain Cancer Center, LLP, Denver,<br />
CO; Georgia Cancer Specialists PC, Sandy Springs, GA; Keryx Biopharmaceuticals, Inc., New York, NY;<br />
University of Texas M. D. Anderson Cancer Center, Houston, TX<br />
Background: Perifosine (P) is an oral, synthetic alkylphospholipid that inhibits or modifies signal<br />
transduction pathways including AKT, NFkB and JNK. A randomized phase <strong>II</strong> study examined P-CAP vs.<br />
CAP in pts with 2nd or 3rd line mCRC. This study showed improvement in mTTP (HR 0.254 [0.117, 0.555])<br />
and mOS (HR 0.370 [0.180,0.763]). Based on these results, a randomized phase <strong>II</strong>I study of P-CAP vs. CAP<br />
with a primary endpoint of overall survival (OS) in pts with refractory mCRC was initiated. Methods: The<br />
study was a prospective, randomized, double-blind, placebo-controlled randomized phase <strong>II</strong>I trial. Eligible<br />
pts had mCRC which was refractory to all standard therapies. Pts randomized 1:1 to Arm A � P-CAP (P<br />
50 mg PO QD � CAP 1000 mg/m 2 PO BID d1-14) or Arm B � CAP (placebo � CAP 1000 mg/m2 PO<br />
BID d 1-14). Cycles were 21 days. Baseline tumor block collection and a biomarker cohort of pts with preand<br />
on-treatment tumor and blood samples were per<strong>for</strong>med. Results: Between 3/31/10 and 8/12/11, 468 pts<br />
were randomized, 234 pts were in each arm. Baseline demographics were balanced between the arms: age<br />
� 65y (A: 65%, B: 58.5%), male (A: 57.7%, B: 53.0%), ECOG PS 0 (A: 39.7%, B: 39.7%), K-ras mutant<br />
(A: 50.4%, B: 51.3%), and median number of prior therapies (A: 4, B: 4). As of 3/19/12, median follow up<br />
was 6.6 months. Median overall survival: Arm A � 6.4 mo, Arm B � 6.8 mo, HR 1.111 [0.905,1.365], p<br />
� 0.315. Median overall survival <strong>for</strong> K-ras WT pts: Arm A � 6.6 mo, Arm B � 6.8 mo, HR 1.020<br />
[0.763,1.365], p � 0.894; K-ras mutant pts: Arm A � 5.4 mo, Arm B � 6.9 mo HR 1.192 [0.890,1.596],<br />
p � 0.238. Conclusions: Despite promising randomized phase <strong>II</strong> data, this phase <strong>II</strong>I study shows no benefit<br />
in overall survival adding perifosine to capecitabine in the refractory colorectal cancer setting. Response<br />
rate, progression free survival, and safety data will be presented. Biomarker analysis is pending to see if<br />
subgroups of patients may have potential benefit.<br />
© 2012 American Society of Clinical Oncology. Reprinted with permission.
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