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`Refining Current Treatments and Looking Ahead in
`HER2-positive Breast Cancer
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`COVER
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`MOST READ
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`DEPARTMENTS
`
`By Caroline Helwick
`September 15, 2012, Volume 3, Issue 14, Bosl of ASCO Supplement
`
`Related Links:
`
`SIDEBAR Does Lapa11n1b Prevent
`CNS Metastases 1n HER2-postt,ve
`Breast Cancer?
`
`SIDEBAR Browstng the Ant1-HER2
`Opt1ons
`
`SIDEBAR A Tough Call The T1
`HER2-pos1t1ve Tumor
`
`Figures:
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`F1g 1. Progresston·free survwal by
`Independent review comm;ltee (IRC)
`and lnvl!.lshgator UJVICW (I NV) In
`EMILIA troal Cap • capoolab1ne Lap
`• 1apahn1b Repnnted w1th ~rm•ss10n
`froll'\ Blackwt~lt 8t al 1
`
`In a study presented at the ASCO Plenary
`Session, trastuzumab emtansine (T-DM1 ),
`the antibody-drug conjugate linking
`trastuzumab (Herceptln) to a cytotoxic
`agent, Improved progression-free survival
`by 3.2 months, representing a 35%
`reduction in risk of progression In the
`phase Ill EMILIA trial. '
`
`EMILIA Study Details
`
`EMILIA randomly assigned 991 HER2-
`pos~ive patients who had locally advanced
`or metastatic breast cancer and who had
`previously received a taxane and
`trastuzumab. Patients received T-DM1 or
`capec~abine (Xeloda) plus lapatinib (Tykerb) every 3 weeks until
`progression . Patients experiencing disease progressoin on standard
`therapy were allowed to cross over to T-DM 1.
`
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`At the time of this presentation , patients receiving T-DM1 had a
`disease-free survival of 9.6 months, vs 6.4 months w~h
`capec~abinellapatinib (P < .0001 ) (Fig. 1).
`
`' T-DM1 readily outpaced capec~abine/lapat in inb . All subgroups had
`relatively comparable benefit," noted Harold J. Burstein, MD, PhD,
`of Dana-Farber Cancer Center, Boston, who presented the findings
`at the Best of ASCO Boston meeting.
`
`Median overall survival was not reached w~h TOM-1, and was 23.3
`months w~h capec~ablnellapatln ib, for a 38% reduction in mortal ~y
`risk that was not statistically significant. More than 65% of the
`T-DM1 recipients were alive at the time of analysis, compared to
`47.5% of the capec~ablnellapatln lb group.
`
`An equally striking difference was in tolerabil ~y. Dose reductions were required for only 16.3% of the
`T-DM1 arm , compared to 53.4% with capec~ab ine and 27.3% w~ lapatinib. Patient-reported
`outcomes were also sign~icantly better with T-DM1 ,
`
`' This is a remarkably well tolerated product, and that's exc~ing ," Dr. Burstein said . ' It lacks the typical
`side effects of chemotherapy because ~s small dose is mostly delivered selectively to the tumor s~e ."
`Because of its strong efficacy and minimal toxic~y . ' T-DM1 will become a standard second-line
`treatment in HER2- pos~ive disease," he predicted .
`
`Editors ' note: New data from the phase Ill EMILIA study were reported in a press release issued by
`Genentech on August 26 2012. These updated resu~s showed that T-DM1 significantly improved
`overall survival In HER2- pos~ ive metastatic breast cancer compared to the combination of lapatinlb
`and capec~abi ne . See the September 15, 2012, Issue of The ASCO Post (page 32) for more
`information, or vis~ ASCOPost.com.
`
`Trastuzumab Superior to Lapatanlb
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`Meanwhile, the phase Ill Canadian MA.31 /GSK EGF 108919 trial compared current anti-HER2 agents
`In the first-line metastatic setting and found trastuzumab to be superior to lapatinib, each given with a
`taxane (weekly paclltaxel or docetaxel every 3 weeks) until progression.' In the study of 652 patients,
`median progression-free survival was 8.8 months with lapatlnib vs 11 .4 months w~h trastuzumab,
`indicating a 33% increased risk of progression w"h lapatinib (P = .01 ). In women with centrally
`confirmed HER2-overexpressing tumors, the difference between the arms approached 5 months (P
`= .003), though overall survival differences have not been observed.
`
`Lapatinlb therapy was associated w"h more adverse events than trastuzumab, most notably diarrhea,
`and more treatment discontinuations.
`
`Combined HER2 Blockade: Best Neoadjuvant Strategy?
`
`Five large trials have shown that trastuzumab plus lapatinib yields higher pathologic complete
`response rates than trastuzumab alone, and the most recent was presented at the ASCO Annual
`Meeting' National Surgical Adjuvant Breast and Bowel Project (NSABP) B-41 involved 529 patients
`who received four cycles of doxorubicin plus cyclophosphamide (AC) followed by weekly paclitaxel (P)
`plus either trastuzumab, lapatinib, or trastuzumab plus lapatinib prior to surgery.
`
`The pathologic complete response rate was 52.5% in the trastuzumab arm, 53.2% in the lapatinlb arm.
`and 62% w"h trastuzumab plus lapatinlb, for a trend favoring the combination (P = .095). By hormone
`receptor status, the combination yielded a numeric, though not a statistically significant, benefit over
`the single agents and was higher among hormone receptor- negative patients (73.0%) than hormone
`receptor- positive patients (55.6%), which Dr. Burstein called an •exc"ing• result tor HER2-pos"ive,
`estrogen receptor-negative disease.
`
`'M1en defined as absence of residual disease in both the breast and nodes. pathologic complete
`responses were achieved by 60.2% w"h the combination, 49.4% with trastuzumab, and 47.4% with
`lapatinlb, for a strong trend favoring the combination (P • .056).
`
`"In B-41 , trastuzumab plus lapatinib was better. Now we have five trials, Including two NCI-supported
`studies, all showing the same resu~ . yet no one is calling the combination an important advantage and
`no one is moving forward with this reg imen." he said. "'M1y? That's a good question with no real
`answer: •
`
`Disclosure: Dr. Burstein reported no potential conflicts of interest.
`
`References
`
`1. Blackwell KL , Miles D, Gianni L, et al: Primary resu~s from EMILIA, a phase 3 study of trastuzumab
`emtansine (T·DM1 ) versus capecitabine and lapatinlb in HER2-positive locally advanced or metastatic
`breast cancer previously treated ~h trastuzumab and a taxane. 2012 ASCO Annual Meeting. Abstract
`LBA 1. Presented June 3, 2012.
`
`2. Gelman K, Boyle F, Kaufman B. et al: Open-label phase Ill randomized controlled trial comparing
`taxane-based chemotherapy w"h lapatininb or trastuzumab as first-line therapy tor women with HER2+
`metastatic breast cancer: Interim analysis of NCIC CTG MA.31/GSK EGF 108919. 2012 ASCO Annual
`Meeting. Abstract LBA671 . Presented June 3, 2012.
`
`3. Robidoux A, Tang G. Rastogi P, et al: Evaluation of lapatinib as a component of neoadjuvant
`therapy tor HER2+ operable breast cancer: NSABP protocol B-41 . 2012 ASCO Annual Meeting.
`Abstract LBA506. Presented June 3, 2012.
`
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`http://www.ascopost.com/issues/september-15-20 12-boa-supplement/refining-current-treat... 5/29/2014
`
`IMMUNOGEN 2023, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676