%u25BA ASCO SPOTLIGHT
When Two “Mabs” Are Better Than One
Investigators from multiple centers in Europe have combined trastuzumab with an investigational agent to treat late-stage breast cancer, with encouraging results.
The HER-dimerization inhibitor pertuzumab was given to patients with HER2-positive breast cancer that had advanced despite treatment with trastuzumab and other chemotherapy. Pertuzumab works by antagonizing the pairing of HER2 protein with other HER receptors. The mechanism of action of pertuzumab may complement that of trastuzumab, leading to the hypothesis that it may be effective in combination.
The study was a phase II trial but not randomized. Each of 33 patients assessed to date had received up to three courses of chemotherapy in addition to trastuzumab before experiencing progression. Once enrolled into this investigation, patients received intravenous pertuzumab 420 mg every three weeks (after a 840-mg loading dose) and trastuzumab 2 mg/kg weekly or 6 mg/kg every three weeks.
The researchers noted a complete response in one patient and partial response in five patients. Seven additional patients experienced disease stabilization.
Also of note, 11 patients received a total of 39 cycles of combined treatment. Five patients experienced leftventricular systolic dysfunction, which resolved in three patients after discontinuation of treatment.
A response rate of 18% is “striking” according to lead author, Jose Baselga, MD, Vall d’Hebron University Hospital, Barcelona, Spain, “and this is potentially good news for patients whose HER2-positive breast cancer is not responding to current treatments.” Larger studies are needed to confirm these results, however.
In related news, a phase III study of the effect of trastuzumab used as neoadjuvant treatment (when combined with chemotherapy) in patients with HER2-positive breast cancer demonstrated that it can contribute to greater use of breast-conserving surgery. When used before surgery, Italian investigators found that trastuzumab plus chemotherapy completely eradicated the tumor in 43% of the 115 patients studied compared with chemotherapy, which eradicated the tumor in 23% of 113 patients. Furthermore, the researchers found that a greater percentage of patients in the trastuzumab group had complete eradication of tumor from the lymph nodes than chemotherapy alone (38% vs. 20%, respectively).
Baselga J, et al: Objective response rate in a phase 2 multicenter trial of pertuzumab, a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab in patients with HER2-positive metastatic breast cancer which had progressed during trastuzumab therapy. Presented at ASCO, June 3, 2007.
Gianni L, et al: Neoadjuvant trastuzumab in locally advanced breast cancer (NOAH): Antitumor and safety analysis. Presented at ASCO, June 3, 2007.
%u25BA ASCO SPOTLIGHT United Kingdom
Evidence Mounts Against Use of Adjuvant External Beam Radiotherapy in Endometrial Cancer
Does adjuvant external beam radiotherapy (EBRT) improve survival in women with endometrial cancer? This therapy has been used for years without a great deal of evidence to support its use. Two study centers, in Canada and the United Kingdom, merged their investigations to obtain convincing data that EBRT after surgery does not affect overall survival.
The study pooled results from 905 women with stage 1 endometrial cancer, of whom 453 were randomized to not receive ERBT, with or without brachytherapy (51% received brachytherapy); 452 were randomized to receive ERBT, and just more than half also had brachytherapy. The study recruited patients from 1996 to 2005.
Nearly all of the patients had World Health Organization performance status of 0 to 1 before treatment. Eighty-three percent of patients demonstrated endometroid histology.
The researchers found that after a mean 51 months of follow-up that treatment-related morbidity was higher in the ERBT arm (56% vs. 24%), though grade 3 toxicity or higher was rare. Five-year survival for both groups was 84%, and the recurrence-free survival for both groups was 87%. A statistically significant difference in isolated vaginal or pelvic recurrence favored ERBT treatment, but this difference was only three percentage points, and did not seem to affect the overall survival.
Orton J, et al: Adjuvant external beam radiotherapy (EBRT) in the treatment of endometrial cancer: Results of the randomised MRC ASTEC and NCIC CTG EN.5 trial. Presented at ASCO, June 5, 2007.
%u25BA ASCO SPOTLIGHT Norway
Clinical Data Suggest Potential Versatility of Pemetrexed for Injection (Alimta)-Based Regimens in Lung Cancer