Adding Trastuzumab to Adjuvant Chemotherapy in Breast Cancer.
Trials of Adjuvant Trastuzumab in HER2+ Early-Stage Breast Cancer Trial Study Regimen No. of...
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Transcript of Trials of Adjuvant Trastuzumab in HER2+ Early-Stage Breast Cancer Trial Study Regimen No. of...
Trials of Adjuvant Trastuzumab in HER2+ Trials of Adjuvant Trastuzumab in HER2+ Early-Stage Breast CancerEarly-Stage Breast Cancer
TrialTrial Study RegimenStudy Regimen No. of No. of PatientsPatients
Disease-Free Disease-Free Survival (%)Survival (%)
Hazard Hazard RatioRatio
PP-Value-Value Overall Overall SurvivalSurvival
Hazard Hazard Ratio Ratio (%)(%)
P-P- ValueValue
NSABP B-31 and NSABP B-31 and NCCTG N-9831NCCTG N-9831
Doxorubicin and cyclophosphamide, Doxorubicin and cyclophosphamide, then paclitaxelthen paclitaxel
16791679 6767 8787
Doxorubicin and cyclophosphamide, Doxorubicin and cyclophosphamide, then paclitaxel plus trastuzumab, then then paclitaxel plus trastuzumab, then trastuzumabtrastuzumab
16721672 8585 0.480.48 <.001<.001 9191 0.670.67 .02.02
NCCTG N-9831NCCTG N-9831 Doxorubicin and cyclophosphamide, Doxorubicin and cyclophosphamide, then paclitaxelthen paclitaxel
979979
Doxorubicin and cyclophosphamide, Doxorubicin and cyclophosphamide, then paclitaxel, then trastuzumabthen paclitaxel, then trastuzumab
985985 0.870.87 .29.29 0.850.85 .48.48
Doxorubicin and cyclophosphamide, Doxorubicin and cyclophosphamide, then paclitaxel plus trastuzumab, then then paclitaxel plus trastuzumab, then trastuzumabtrastuzumab
840840 0.640.64.48.48
.01.01<.01<.01
0.740.74 .27.27
HERAHERA ObservationObservation 16981698 7474 9090
Trastuzumab for 1 yearTrastuzumab for 1 year 17031703 8181 0.640.64 <.001<.001 9292 0.660.66 .011.011
BCIRG 006BCIRG 006 Doxorubicin and cyclophosphamide, Doxorubicin and cyclophosphamide, then docetaxelthen docetaxel
10731073 7373 8686
Doxorubicin and cyclophosphamide, Doxorubicin and cyclophosphamide, then docetaxel plus trastuzumab, then then docetaxel plus trastuzumab, then trastuzumabtrastuzumab
10741074 8484 0.490.49 .001.001 9292 0.590.59 .004.004
Docetaxel, carboplatin, and trastuzumabDocetaxel, carboplatin, and trastuzumab 10751075 8080 0.610.61 <.01<.01 9191 0.660.66 .02.02
FinHerFinHer ChemotherapyChemotherapy 116116 7878 9090
Chemotherapy plus trastuzumabChemotherapy plus trastuzumab 116116 8989 0.420.42 .01.01 9696 0.410.41 .07.07
With permission from Hudis CA. N Engl J Med. 2007;357:39-51.
ALTTO ALTTO Formerly Known as APHRODITEFormerly Known as APHRODITE
Randomize
Trastuzumab x 1 year
Lapatinib x 1 year
+ lapatinib x 1 year
Trastuzumab x 1 year
Inclusion Criteria• HER2+ breast cancer• ≥4 cycles anthracycline-based neoadjuvant chemotherapy• LVEF ≥50%
Clinicaltrials.gov. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00490139?term=A.Accessed on: September 15, 2009. ALLTOTRIALS.COM—Trial Overview. Available at: http://www.alttotrials.com/patients.php#5. Accessed on: September 15, 2009.
Trastuzumab x 12 weeks
Break 6 weeks
Lapatanib x 34 weeks
Targeting HER2+ TumorsTargeting HER2+ Tumors
With permission from Burstein HJ. N Engl J Med. 2005;353:1652-1654.
InhibitKinaseActivity
InhibitDimerization
ModerateReceptorExpression
PotentiateDownstreamEffects
RefineAntibodies
Mechanism of Cell Death from Inhibition Mechanism of Cell Death from Inhibition of Polyadenosine Diphosphate-Ribose of Polyadenosine Diphosphate-Ribose
Polymerase 1 (PARP-1)Polymerase 1 (PARP-1)
With permission from Iglehart JD, et al. N Engl J Med. 2009;361:189-191.
Radiologic Evidence of Tumor Radiologic Evidence of Tumor Response to OlaparibResponse to Olaparib
With permission from Fong PC, et al. N Engl J Med. 2009;361:123-134.
Patient 20at Baseline
Patient 41at Baseline
Patient 20at 4 Months
Patient 41at 4 Months
A
BevacizumabBevacizumabSummary of Breast Cancer StudiesSummary of Breast Cancer Studies
Median Progression-Free Survival
Study ChemotherapyChemotherapy +
Bevacizumab P-Value
Miller1 (capecitabine ± bevacizumab)
4.17 months 4.86 months P = .857
AVADO2 (docetaxel ± bevacizumab)
8.0 months
9.0 months with 7.5 mg/kg bevacizumab10.0 months with 15 mg/kg bevacizumab
P = .0164P = .0002
E21003 (paclitaxel ± bevacizumab)
5.9 months 11.8 months P <.001
RIBBON-14
(taxane/anthracycline ± bevacizumab)
8.0 months 9.2 months P <.0001
RIBBON-14 (capecitabine ± bevacizumab)
5.7 months 8.6 months P = .0002
1. Miller KD, et al. J Clin Oncol. 2005;23:792-799. 2. Miles D, et al. 44th ASCO; May 30-June 3, 2008. Abstract LBA1011. 3. Miller K, et al. N Engl J Med. 2007;357:2666-2676. 4. Robert NJ, et al. 45th ASCO; May 29-June 2, 2009. Abstract 1005.
VEGF Signaling Pathway in AngiogenesisVEGF Signaling Pathway in Angiogenesis
With permission from Kerbel RS. N Engl J Med. 2008;358:2039-2049.
NSABP B-20 OutcomeNSABP B-20 Outcomeby Recurrence Scoreby Recurrence Score
With permission from Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
Overall
Intermediate risk: 18–30
Low risk: <18
High risk: >30
Oncotype DX recurrence score tends to correlate Oncotype DX recurrence score tends to correlate with established breast cancer prognostic/with established breast cancer prognostic/predictive factorspredictive factors
– AgeAge
– Tumor gradeTumor grade
– HER2HER2
– Quantitative ER/PR levelsQuantitative ER/PR levels
– Tumor sizeTumor size
The “poor man’s” Oncotype DXThe “poor man’s” Oncotype DX
– TN stage, grade, ER, PR, HER2TN stage, grade, ER, PR, HER2
Oncotype DX, Breast Cancer Assay. Available at: www.oncotypedx.com. Accessed on: September 14, 2009.
Oncotype DX Breast Cancer Assay
Multigene Arrays and Prediction of Multigene Arrays and Prediction of Relapse-Free Survival in Breast CancerRelapse-Free Survival in Breast Cancer
With permission from Fan C, et al. N Engl J Med. 2006;355:560-569.