“Trastuzumab with neoadjuvant chemotherapy before surgery improves response rates for HER2 positive breast cancer”: This abstract, presented at last month’s meeting in Berlin, reports the results from the GeparQuattro trial that enrolled 1510 patients with breast cancer (BC), 453 of whom had HER2-positive disease. Prior to surgery, all patients received 4 cycles of epirubicin/cyclophosphamide (EC) and were then randomized to receive either 4 cycles of docetaxel (D), 4 cycles of D+capecitabine (DX), a combination of both D and DX, or 4 cycles of D followed by 4 cycles of DX. Women with HER2-positive tumors also received trastuzumab at the same time as the neoadjuvant chemotherapy, and then continued the trastuzumab (T) after surgery for up to one year. Both the chemotherapy and the T were given via 3-weekly infusions. To minimize the risk of cardiotoxicity, patients with any previous heart conditions and patients with ejection fractions less than 55% were excluded. All patients treated with neoadjuvant chemo+T received cardiac monitoring every 3 months.

Data were analyzed 15 months after the start of the trial and researchers found that women with HER2-positive disease treated with both chemotherapy and T had a pathologic complete response rate (pCR, complete disappearance of cancer cells from the breast) of 41.3% compared to a pCR of 19.5% in women who had not received trastuzumab. Toxicity analysis results showed no increase in toxicity for the combination chemotherapy plus T compared with chemotherapy alone. No cases of CHF or cardiac-related deaths were seen, and other cardiac-related symptoms were not severe.

Gender-related differences in colon cancer are recognized, such as lower rates of the disease in women and gender-related response to treatment. Expression of epidermal growth factor receptor (EGFR) has been linked with a worse prognosis, but up until now, it was assumed that variants of the gene had a similar effect in men and women. However, the results of a new study published in the April 15, 2008, issue of Cancer Research shows that whether variant forms of EGFR increase or decrease survival in patients with colon cancer depends on their gender.

Researchers studied two variant forms of EGFR, one with a change at codon 497 and the other with a change at intron 1. To examine the effects of the variants on survival, they analyzed DNA from 318 patients with advanced colon cancer who had all received similar treatment. When all 318 patients (177 men, 141 women) were considered, the EGFR variants did not influence survival. However, when men and women were analyzed separately, the variants affected survival differently. In men, the codon 497 variant decreased the median overall survival (OS) from 13.7 months to 10.3 months. In women however, the variant increased median OS from 14.0 months to 16.0 months. The intron 1 variant also acted differently in men vs women. In men, median OS rose from 10.3 months to 13.1 months with the variant, but in women it fell from 17.6 months to 14.1 months. Researchers feel these differences may relate to how the EGFR protein interacts with male and female hormone receptors in the colon. They suggest that gene variants should be evaluated differently in women and men, and that treatment decisions may depend on gender and not only on clinical findings.

This item is more of a “heads-up” or “FYI” than anything, but worth a mention. The March 2008 issue of the British Journal of Urology International includes an article reporting the association between renal cell carcinoma (RCC) and multiple myeloma (MM). Between 1990 and 2005, the Cleveland Clinic was referred 1100 patients with MM, 2704 with RCC, and 8 patients with both types of cancer. In 4 of the 8 patients, RCC was diagnosed 3 to 46 months after the MM diagnosis. In the remaining 4, RCC was diagnosed 1 to 108 months before the MM. Seven of the eight patients were first diagnosed with RCC on the right side. The researchers note that the probability of this association was much higher than that in the general population. They state that no clear treatment-related, environmental, genetic, or immune-mediated common factors can fully explain this association. Investigators did point out that interleukin-6 supports the growth and progression of both malignancies. When MM was the first malignancy diagnosed, the RCC was at a very early stage, therefore surgical exploration is critical.

ImClone Systems has reached agreement with the FDA under a Special Protocol Assessment (SPA) for its planned phase III clinical trial of IMC-1121B, an anti-vascular endothelial growth factor receptor-2 (anti-VEGFR-2) fully human IgG1 monoclonal antibody, in women with metastatic breast cancer (MBC). The trial will be a randomized, double-blind, placebo-controlled study comparing IMC-1121B plus docetaxel with placebo plus docetaxel in 1100 women with unresectable locally-recurrent or MBC who have not received prior chemotherapy in that clinical setting. The primary endpoint is progression-free survival (PFS). Patient enrollment is expected to begin in the third quarter of 2008.

A data safety monitoring board (DSMB) has reviewed blinded safety data from a phase III trial of Genta’s oblimersen sodium (Genasense^®) in advanced melanoma and deemed the study fit to continue as planned. The randomized, multinational, double-blind, placebo-controlled AGENDA trial with a target enrollment of 300 chemotherapy-naïve patients with advanced melanoma and low LDH (≤ 0.8 x ULN). Patients will be randomized to treatment with either dacarbazine (DTIC) plus oblimersen sodium or dacarbazine plus placebo with safety and efficacy evaluated. Primary endpoints are PFS and OS. The company anticipates meeting its target enrollment by the fourth quarter of the year. In a previously completed phase III trial of 771 patients with advanced melanoma treated with DTIC +/- oblimersen sodium, LDH level predicted for survival outcomes with significant improvement in both OS and PFS in patients with normal LDH (≤ 1.1 x ULN). This current study seeks to confirm the findings from the earlier study and is being performed to prospectively assess the efficacy of DTIC plus oblimersen sodium in chemotherapy-naïve patients with advanced melanoma and baseline LDH ≤ 0.8 x ULN.

Novartis has started a pivotal phase III trial of ASA404 (DMXAA), a small molecule tumor vascular disrupting agent (Tumor-VDA) that targets established tumor blood vessels causing apoptosis of tumor endothelial cells, in combination with paclitaxel and carboplatin as a first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The randomized, double-blind, placebo-controlled, multicenter ATTRACT-1 study will build on supportive data from phase II trials. In a randomized phase II trial in lung cancer which included patients with stage IIIB/IV NSCLC, the combination of ASA404 plus paclitaxel and carboplatin produced a median survival of 14.0 months compared to 8.8 months for chemotherapy alone.

It has been my pleasure to serve as the OncoFacts newsletter editor since May 2000. The time has come for me to move on and pursue other interests.

It is also my pleasure to introduce Christy Russell, MD, as the new OncoFacts Editor beginning in June. Dr Russell is an associate professor of medicine at the Keck School of Medicine at the University of Southern California. She has contributed to many of our meetings and e-learning activities over the past several years as a moderator and faculty member. We welcome Dr Russell to the OncoFacts, and I encourage you to continue your support of this informative newsletter.

OncoFacts™ Editor:

Jim Jones, MD

For ongoing improvement, we would appreciate your comments and suggestions. Email your suggestions to: elearning@imedex.com

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