Annual Meeting

AM 2012 Daily News Monday Sec A

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MONDAY · JUNE 3, 2012 R esults of two phase III trials pre- sented during Saturday's Oral Abstract Session on gynecologic cancer provide new directions for the optimal treatment of women with advanced ovarian cancer. Eric Pujade-Lauraine, MD, PhD, of Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINE- CO) and the Université Paris Descartes, France, speaking on behalf of the AURE- LIA investigators, presented results from the fi rst phase III trial combining the monoclonal antibody bevacizumab with standard-of-care chemotherapy for the treatment of platinum-resistant recur- rent ovarian cancer (Abstract LBA5002). Women eligible for the trial had ovar- ian cancer that progressed within 6 months of completing at least 4 cycles of platinum-based therapy and had no history of bowel complications. Chemo- therapy was selected by the investiga- tor based on each woman's prior drug exposure, and options included stan- dard-of-care drugs pegylated liposomal doxorubicin (PLD), topotecan, or weekly paclitaxel. Women were randomly as- signed to receive standard chemothera- py alone or in combination with bevaci- zumab until progression or unacceptable toxicity, with 182 receiving standard INSIDE MONDAY SECTION A ALK Inhibitor Highly Active in Crizotinib- Refractory ALK-Positive NSCLC Regimens Compared for Active Follicular Lymphoma More Effective Therapies Elusive in Esophageal Cancer Maintenance Erlotinib Does Not Improve Ovarian Cancer Survival Navigating Multiple Myeloma Induction, Transplant, and Maintenance PISCES: Pazopanib Preferred for Metastatic RCC High-Dose BEACOPP Not Warranted for All Patients with High-Risk Hodgkin Lymphoma Benefi ts for Combination Therapy Not Realized in Phase III Study for Metastatic Colorectal Cancer Lapatinib as Component of Neoadjuvant Therapy for HER2-Operable Breast Cancer Tivantinib Holds Promise for MET-Expressing Unresectable Hepatocellular Carcinoma Biomarker in Older Adults with Malignant Astrocytomas 3A 4A 4A 6A 9A 10A 10A 12A 14A 14A 15A DAILY NEWS SECTION Discussant Dr. Michael Seiden offered radical considerations regarding cessation of phase III trials due to the absence of large groups of similar patients. chemotherapy and 179 receiving beva- cizumab in addition. Those in the con- trol arm could cross over to bevacizumab monotherapy at disease progression. Median follow-up was 13.9 months for women receiving standard chemothera- py and 13 months for the bevacizumab group, and the two treatment groups had similar baseline characteristics. Median progression-free survival (PFS) was 3.4 months for those receiving standard chemotherapy alone and 6.7 months for those receiving bevacizumab (hazard ratio [HR]: 0.48; 95% CI [0.38 – 0.60]; p < 0.001), as seen in Figure 1. Subgroup analysis indicated that the addition of bevacizumab to standard chemotherapy improved progression- free survival regardless of age, relapse- free interval, extent of disease, presence of ascites or type of chemotherapy ad- ministered. The 12.6% response rate in the standard chemotherapy group was about what was expected in this patient population , whereas the response rate in the bevacizumab-treated group was sig- nifi cantly improved, whether evaluated by response evaluation criteria in solid tumors (RECIST) or by CA-125 levels (p = 0.001 in RECIST; p < 0.001 in CA-125). The safety profi le of bevacizumab was consistent with previous clinical expe- rience. Hypertension and proteinuria (grade 2 or worse) were more frequent in the bevacizumab-treated group, 27% compared with 8% in the control group, and 12% compared with 1%, respective- ly; fatigue, abdominal pain, vomiting, and dyspnea occurred less frequently in the group treated with bevacizumab. Overall, seven women receiving beva- Studies Report Progress in the Treatment of Advanced Ovarian Cancer A cizumab experienced gastrointestinal perforation, and six had fi stulas or ab- scesses. The incidence of peripheral sensory neuropathy and of hand-foot syndrome (grade 3 or worse) was higher in the bevacizumab-treated patients, perhaps because more patients were responding, and thus they received more chemo- therapy. In the cohort receiving PLD, the time-course for the cumulative inci- dence of hand-foot syndrome was simi- lar in the two study groups. Likewise, in the cohort receiving paclitaxel, the time- course for the cumulative incidence of neuropathy was similar. Dr. Pujade-Lauraine concluded that, because AURELIA is the fi rst random- ized phase III trial to demonstrate ben- efi t with biologic therapy and benefi t with combination therapy, rather than monotherapy for women with plati- num-resistant ovarian cancer, bevaci- zumab combined with chemotherapy should be considered a new standard-of- care option. In his discussion, Michael Seiden, MD, PhD, of Fox Chase Cancer Center, offered some provocative observations about the treatment of ovarian can- cer. Dr. Seiden posited that because the See Advanced Ovarian Cancer, Page 12A Trastuzumab Is Superior to Lapatinib as First-Line Therapy for HER2-Positive Metastatic Breast Cancer T rastuzumab prolongs progression- free survival (PFS) compared with lapatinib when added to taxane- based fi rst-line therapy for women with HER2-positive metastatic breast cancer. Karen A. Gelmon, MD, of the Brit- ish Columbia Cancer Agency, Canada, presented the interim analysis of the Na- tional Cancer Institute of Canada Clini- cal Trials Group protocol MA.31/GSK EGF 108919 during yesterday's Breast Cancer Oral Abstract Session (Abstract LBA671). The Data Safety and Monitor- ing Committee for this study recom- mended disclosure of the results because the superiority boundary was crossed. This phase III trial compared taxane- based therapy (weekly paclitaxel or docetaxel every 3 weeks for 24 weeks) in combination with lapatinib or trastu- zumab. The oral lapatinib dose was 1,250 mg daily during taxane therapy followed by 1,500 mg daily until disease progression. After a loading dose, the trastuzumab dose was 2 mg/kg weekly or 6 mg/kg every 3 weeks during taxane therapy followed by 6 mg/kg every 3 weeks until progression. There was a potential for follow-up bias, because women in the trastuzumab group visited the clinic every 3 weeks for therapy, whereas women in the lapa- tinib group came in for follow-up every 4 weeks. The two groups were well balanced for baseline characteristics. Approxi- mately 40% of the women in each treat- ment arm had metastatic breast cancer at primary diagnosis; 18% had received trastuzumab and approximately 20% had received a taxane in the adjuvant or neoadjuvant setting. Forty-six percent of the women had liver metastases. In the intention-to-treat analysis, me- dian PFS for women taking lapatinib was 8.8 months compared with those receiv- ing trastuzumab (11.4 months), with a hazard ratio of 1.33 (95% CI: 1.06–1.67; p = 0.01, Fig. 1). A more rigorous analysis was conducted on the subset of women with centrally confi rmed HER2-positive tumors (Fig. 2). PFS was 13.7 months in Fig. 1. 100 80 60 40 20 0 # TTAX/T # LTAX/L Progression-Free Survival Intent to Treat Analysis Median PFS TTAX/T = 11.4 months Median PFS LTAX/L = 8.8 months HR = 1.33 (95% CI: 1.06–1.67), p = 0.01 # TTAX/T # LTAX/L 318 318 0 223 218 510 110 85 44 35 15 21 13 20 Time (months) Abbreviations: PFS, Progression-free survival; TTAX/T, trastuzumab/taxane followed by trastuzumab monotherapy; LTAX/L, lapatinib/taxane followed by lapatinib monotherapy; HR, hazard ratio; CI, confi dence interval the trastuzumab arm and 9.0 months in the lapatinib arm for these patients (HR = 1.48, 95% CI: 1.15–1.92; p = 0.003). No difference in overall survival was detected (HR = 1.1, 95% CI: 0.75–1.61; p = 0.62). Lapatinib therapy was associated with more adverse events than trastuzumab; 17.8% of the women who received lapa- tinib discontinued the protocol therapy as a result of toxicity, compared with See Metastatic Breast Cancer, Page 4A 25 8 2 30 1 0 35 0 0 40 0 0 Percentage

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