Second Opinion

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Track 21DR LOVE: Dan, how would you approach treating this patient?DR HAYES: A number of philosophical approaches to this patient are available.One is to acknowledge that she has metastases, and the treatment is palliation.Therefore, one should choose the treatment most likely to be effective withthe fewest side effects. I tell patients, “The bad news is that you have metastaticbreast cancer, and we will probably not cure you. The good news is that wehave many therapeutic options.” Many of those options are interchangeable, sodefining a treatment plan entails working with the patient and the family to findout what’s best for the individual.This patient has ER/PR-positive, HER2-positive disease, and I would probablyinitiate treatment with endocrine therapy. It would be reasonable to start her ontamoxifen. One could also argue in favor of tamoxifen with trastuzumab, butthat would require her to come to the clinic every three weeks for intravenoustherapy. Others might opt for ovarian ablation in combination with tamoxifen,which results in a higher response rate but no improvement in survival.DR LOVE: What about chemotherapy and trastuzumab?DR HAYES: This woman is in no danger of dying of her disease in the nexttwo months or of developing substantial end-organ dysfunction that wouldprohibit the administration of chemotherapy and trastuzumab down the road. Isee no evidence that she would live longer by receiving up-front chemotherapy/trastuzumab, but she would be subjected to toxicities that could be avoided forthe time being. If an oncologist wanted to use chemotherapy/trastuzumab, Iwouldn’t argue strongly against it, but it’s not what I would do.Track 3DR LOVE: One of the most discussed issues in the management of HER2-positive metastatic breast cancer is continuation of trastuzumab or otheranti-HER2 therapy on disease progression. Joyce, what are your thoughts?DR O’SHAUGHNESSY: Some of the most important data from ASCO last yearaddressed the question, does continuing trastuzumab beyond disease progressionprovide a clinical benefit? I had the opportunity to present data from a Phase IIItrial for patients with HER2-positive metastatic breast cancer who were heavilypretreated with an anthracycline, a taxane and trastuzumab (O’Shaughnessy2008; [1.1]). Approximately one third of the patients had received six or moreregimens for metastatic disease.Upon disease progression, patients were randomly assigned to lapatinib at 1,500milligrams or lapatinib at 1,000 milligrams in combination with weekly trastuzumab.The hazard ratio for progression-free survival, which was the primaryendpoint, was 0.73, so the combination was clearly superior to switching to adifferent HER2-targeted therapy, single-agent lapatinib.4
In another trial addressing this question, patients with HER2-positive metastaticbreast cancer that had progressed through one line of trastuzumab-based therapywere randomly assigned to capecitabine with or without trastuzumab (vonMinckwitz 2008; [1.2]).The combination yielded nearly double the objective response rate, a 50 percentimprovement in the clinical benefit rate, a significant improvement in progression-freesurvival and a trend for improvement in overall survival. So this trialfavored continuation of trastuzumab and simply switching the chemotherapyupon disease progression.DR WINER: The von Minckwitz study probably underestimated the benefitof continuing trastuzumab because the women who received capecitabinemonotherapy still had trastuzumab in their system (von Minckwitz 2008). Thatstudy, along with Joyce’s data with the combination of lapatinib and trastuzumab(O’Shaughnessy 2008), confirm that, at least for some patients, a role does existfor continuing trastuzumab after disease progression.1.1Lapatinib (L) with or without Trastuzumab (T) for HeavilyPretreated Patients with Metastatic Breast Cancer ExperiencingDisease Progression on Trastuzumab TherapyLL + TParameter (n = 145) (n = 146) Odds ratio p-valueResponse rate 1 6.9% 10.3% 1.5 0.46Clinical benefit rate 2 12.4% 24.7% 2.2 0.01Hazard ratiop-valueMedian PFS 8.1 weeks 12.0 weeks 0.73 0.008Median overall survival 3 39.0 weeks 51.6 weeks 0.75 0.1061Confirmed complete responses (CR) + partial responses (PR); 2 CR + PR + stable disease ≥6 months; 3 Intent-to-treat population; PFS = progression-free survival; Odds ratio > 1, hazardratio < 1 favors L + TSOURCE: O’Shaughnessy J et al. Proc ASCO 2008;Abstract 1015.1.2Phase III Study of Capecitabine (X) versus Capecitabine/Trastuzumab(XH) for Patients with HER2-Positive Metastatic Breast CancerProgressing During Trastuzumab TherapyEndpoint X (n = 78) XH (n = 78) p-valueTime to progression 5.6 months 8.2 months 0.03Overall survival 20.4 months 25.5 months Nonsignificant trendResponse rate 27% 48% 0.01Clinical benefit rate 54.0% 75.3% 0.007SOURCE: Von Minckwitz G et al. Proc ASCO 2008;Abstract 1025.5
Page 1 and 2: Second OpinionProceedings and Inter
Page 3 and 4: Second Opinion: Proceedings from a
Page 5: MANAGEMENT OF METASTATIC BREAST CAN
Page 9 and 10: I’m impressed with nab paclitaxel
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Page 15 and 16: From the practice of Isaac Levy, MD
Page 17 and 18: From the practice of Samuel N Bobro
Page 19 and 20: DR SLEDGE: It was an absolutely won
Page 21 and 22: EDUCATIONAL ASSESSMENT AND CREDIT F
Page 23 and 24: ModeratorManaging EditorScientific

Second Opinion

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