Pharmacy & Therapeutics - November 2008 - (Page 668)

MEETING HIGHLIGHTS: ESMO and ASBMR achieved a reduced tumor volume. The safety profile, he said, was acceptable. He added: The most important finding is that you can give the drug to patients with early-stage disease. It is safe, well tolerated, and it does not in any way change or alter their suitability for surgery. The final, remarkable and unexpected result was that 30 out of 35 patients in the study had tumor shrinkage despite the short-term nature of the treatment. “This is a phenomenally innovative study,” said Dr. Baselga, briefing moderator and president of ESMO. “This research could really facilitate the work of surgeons and could help increase cure rates.” 10.6 months by central review and 10.15 months by investigator assessment and had not been reached in the combination group. At six months, progression-free survival by central review was 9.3 months for RAD001 and 12.9 months for RAD001/Sandostatin LAR. Median overall survival had not been reached in either group. Dr. Yao characterized the risk–benefit ratio as positive. He stated that with RAD001 being active as both monotherapy and in combination with Sandostatin LAR in refractory pancreatic neuroendocrine tumors, further investigation is warranted. Lapatinib (Tykerb) for Squamous Cell Head and Neck Cancer • Maria Del Campo, MD, Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain In another trial of an investigative agent in advanced disease, Dr. Del Campo reported promising findings for the tyrosine kinase inhibitor lapatinib (Tykerb, GlaxoSmithKline) in advanced squamous cell carcinoma (SCC) of the head and neck. “Lapatinib improved response to chemoradiation,” Dr. Del Campo said. In the phase 2 randomized trial, investigators assigned 107 therapy-naive patients with locally advanced head and neck cancer to receive oral lapatinib 1,500 mg or placebo for two to six weeks, followed by standard treatment with concurrent platinum-based chemotherapy and radiation. Subjects were followed for 12 weeks after they completed chemoradiation. Dr. Del Campo reported that treatment was well tolerated. There was a modest but statistically significant reduction in mean tumor cell proliferation in the lapatinib patients (–8%) compared with the placebo patients (–2.7%) (P = 0.039). In the subset of 40 patients who underwent radiological scanning after lapatinib monotherapy, 17% achieved complete or partial responses, compared with none of the patients in the placebo arm. Among 88 patients evaluable for radiological analysis after completing chemoradiation, 86% of lapatinib-treated subjects and 63% of placebo subjects achieved complete and partial responses. Response rates following chemoradiation differed between the two groups: 28% of lapatinib patients achieved complete responses, compared with 7% of placebo patients. The results suggested that lapatinib might be enhancing the therapeutic effects of subsequent chemoradiation. Dr. Del Campo concluded that lapatinib alone showed encouraging activity. Phase 3 studies of lapatinib for head and neck cancer are now recruiting patients, she said. Everolimus (Certican) for Pancreatic Tumors • James C. Yao, MD, MD Anderson Cancer Center, Houston, Tex. In a study led by Dr. Yao, everolimus (RAD001, Certican, Novartis), a derivative of sirolimus (Rapamycin, Wyeth), when combined with octreotide acetate (Sandostatin LAR Depot, Novartis), a somatostatin analogue (and the standard treatment for controlling symptoms of refractory pancreatic neuroendocrine tumors), yielded more than double the progression-free survival of historical treatment. RAD001 is an oral inhibitor of the mammalian target of rapamycin (mTOR) with broad antitumor activity. In Dr. Yao’s phase 2 study, 115 patients were randomly assigned to receive RAD001 alone at a dose of 10 mg/day and 45 patients received RAD001 10 mg/day plus Sandostatin LAR at a dose of 30 mg or less every 28 days. The primary endpoint of the study was the objective response rate; secondary endpoints included duration of response, safety, progression-free survival, and survival. Treatment was well tolerated. The most common grade 3 adverse events thought to be related to treatment were asthenia, fatigue, and thrombocytopenia. Five patients in the RAD001 group and four patients in the combination group discontinued therapy because of adverse events. The median age was 55 years in both groups. By central review, objective response rates (according to RECIST, a standard measure of tumor response) were 7.8% for RAD001 and 4.4% for RAD001/Sandostatin LAR. All responses were partial. Investigator assessment, however, placed the objective response rate at 7% for RAD001 and at 8.9% for RAD001/Sandostatin LAR. Stable disease rates, as measured by central review, were 68.7% for RAD001 and 77.8% for RAD001/Sandostatin LAR; these rates, as assessed by the investigators, were 66.1% for RAD001 and 71.1% for the combination, respectively. Clinical benefit rates (partial response plus stable disease) were 76.5% and 82.2% by central review and 73% and 80% by investigator assessment, respectively. Showing the clearest advantage for RAD001/Sandostatin LAR, progressive disease rates by central review were 13.9% for RAD001 alone and 2.2% for the combination. By investigator review, they were 18.3% for RAD001 alone and 11.1% for the combination. Median duration of response for RAD001 was Antibody CP-751871 for Non–Small-Cell Lung Cancer • Luis Paz-Ares, MD, PhD, Chief, Division of Medical Oncology, Virgen del Rocio University Hospital, Seville, Spain Compared with chemotherapy (paclitaxel plus carboplatin) alone, Pfizer’s insulin-like growth factor type-I receptor (IGFIR) antibody CP-751871 improved response rates in patients with NSCLC. The greatest benefit was seen in patients with the squamous cell subtype. 668 P&T® • November 2008 • Vol. 33 No. 11

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - November 2008

Pharmacy & Therapeutics - November 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Heparin-Induced Thrombocytopenia Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched From Fixed-Dose to Free-Combination Antihypertensive Therapy European Society for Medical Oncology and Association for the Study of Bone and Mineral Research Pharmaceutical Approval Update

Pharmacy & Therapeutics - November 2008

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.