Genitourinary Cancer Symposium

Prostate Cancer-Specific Survival in Men with Biochemical Recurrence After Radical Prostatectomy: Impact of Salvage Radiotherapy  vs. Observation. Trock B, et al.

This retrospective study analyzed survival of 635 men treated at Johns Hopkins who developed prostate cancer (PCa) recurrence after radical prostatectomy (RP). Most men (n = 397) received neither salvage radiotherapy (RT) nor hormonal therapy, 160 underwent salvage RT alone, and 78 received both. Over the median follow-up of 6 years after recurrence, 18% of the men died of PCa.

The effect of salvage RT appeared to differ by prostate-specific antigen (PSA) doubling time (p<0.0001). Nearly all patients with a doubling time of 6 months or more survived to 5 years, regardless of RT after recurrence (98% for both). Men at a higher risk with a doubling time of less than 6 months had just as good 5-year survival if they had salvage RT (95%, hazard ratio [HR] 0.14), but survival decreased substantially—to 60%—among those who did not receive RT. Ten-year survival showed a similar benefit for radiation: it was more pronounced among those with faster doubling times (86% vs 75% for doubling time of 6 months or longer and 82% vs 30% with doubling time of less than 6 months). The 10-year prostate cancer-specific survival was substantially higher for men given salvage RT alone (86%) or with hormonal therapy (82%) than for those who received no salvage therapy (62%), p< 0.0001; this advantage extended even to those patients who waited for up to 2 years after biochemical recurrences to start RT. Early salvage treatment was critical: salvage RT improved prostate cancer-specific survival only if given less than 2 years after biochemical recurrence (a rising PSA level).

The authors emphasized that these findings were preliminary because of the retrospective nature of the study. A clinical trial is needed to validate the results.

Selection Bias for Patients Undergoing Nephrectomy for Small Renal Tumors. Huang WC, et al.

According to a large population-based study using data from the SEER cancer registry linked with Medicare claims to find factors predictive of type of surgery offered, researchers found that only 19% of patients with kidney tumors smaller than 4 cm were offered partial nephrectomy. Women, older patients, and those with cerebrovascular disease were disproportionately more likely to undergo radical nephrectomy. This operation has been the gold standard for 60 years with a cure rate better than 90% for these small tumors.

Partial nephrectomy, however, has been shown to yield similar recurrence rates and cancer-specific survival for tumors up to 7 cm. It is considered a standard of care for tumors smaller than 4 cm, although it can be more technically challenging and increases the risk of bleeding and urinary fistula complications. The author’s group previously found significantly increased risk of chronic kidney disease among patients undergoing a radical nephrectomy and more recently showed that the radical operation also caused significant decrease in kidney function.

Among the patients with renal tumors smaller than 4 cm, 81% (2,547 patients) had radical surgery and 19% (556 patients) had the partial nephrectomy. The type of operation did not differ by geographic location, economic level, or race. However, partial nephrectomy was more likely among patients who were younger, male, married, and treated later during the 8-year study period. Renal insufficiency predicted radical nephrectomy as less likely than partial nephrectomy (odds ratio [OR] 0.66, p=0.009), which suggested that less aggressive surgery is increasingly used. Radical surgery was more likely than partial nephrectomy among older patients (OR 1.43, p<0.001), women (OR 1.31, p=0.011), and patients with cerebrovascular disease (OR 1.413, p=0.019). Author conclusions: 1. The reason for these disparities is uncertain. 2. Education of both patients and physicians are required to change the current practice patterns.

Industry News

FDA Actions

On February 22, 2008, the US Food and Drug Administration (FDA) granted accelerated approval for Genentech’s bevacizumab (Avastin^®) to be used in combination with paclitaxel for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer (BC). The approval was based on the demonstration of an improvement in progression-free survival (PFS) in patients receiving bevacizumab with paclitaxel compared to those receiving paclitaxel alone as a first-line treatment for metastatic breast cancer (MBC). No data are currently available that demonstrate an improvement in disease-related symptoms or increased overall survival (OS) with bevacizumab in BC.

The efficacy and safety of bevacizumab as first-line treatment of patients with MBC was studied in Study 7 or E2100. Patients who had not received chemotherapy for locally recurrent or MBC were randomized to either paclitaxel (N = 354) alone or in combination with bevacizumab. Patients with HER2-overexpressing BC were not eligible unless they had received prior therapy with traztuzumab. The addition of bevacizumab to paclitaxel resulted in an improvement in PFS with no significant improvement in OS. The median PFS was 11.3 months vs 5.8 months for the bevacizumab plus paclitaxel arm vs paclitaxel alone arm, respectively (p<0.0001, HR 0.48). Partial response rates in patients with measurable disease were higher with the combination arm: 48.9% vs 22.2% (p<0.001).

The efficacy and safety of bevacizumab as a second-line and third-line treatment of patients with MBC were studied in a single open-label randomized trial (Study 8 or AVF 2119). Patients who had received prior anthracycline and taxane therapy in the adjuvant setting or for their MBC were randomized to receive either capecitabine alone or in combination with bevacizumab. The study enrolled 462 patients. The study failed to demonstrate a statistically significant effect on OS or PFS. The product labeling specifies that bevacizumab is not indicated for patients with BC that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease.

On February 28, 2008, an independent data monitoring committee (IDMC) stopped a major phase III trial of Novartis Pharmaceuticals Corporation’s everolimus (RAD001) after interim results showed significantly better PFS in patients with metastatic clear cell renal cell carcinoma who received everolimus compared to placebo. The randomized, multicenter RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) trial of more than 400 patients included patients whose disease progressed despite receiving approved treatments for renal cell carcinoma (RCC) with other targeted agents such as sorafenib (Nexavar^®), sunitinib (Sutent^®), or both. In addition, patients who had prior targeted therapy with bevacizumab (Avastin^®) and interferon were also allowed in the trial. Based on the results, investigators will offer everolimus to trial patients who are still talking placebo.

Everolimus is an oral inhibitor of mTOR, a protein that acts as a central regulator of tumor cell division, cell metabolism, and blood vessel growth in cancer cells. Once-daily oral therapy provides continuous inhibition of mTOR. Complete results of the RECORD-1 trial will be submitted as a late-breaking abstract for presentation at the 2008 American Society of Clinical Oncology^® annual meeting in May. The company will seek regulatory filings for this indication beginning with US and EU in the second half of 2008.

Symposia

We invite you to attend the accredited educational symposia that will be held at some of the large international meetings in the coming months:

• European Breast Cancer Conference
  April 17th in Berlin, Germany
  “Current and Novel Chemotherapeutic Options in Breast Cancer”
• Oncology Nursing Society Annual Meeting
  May 16 in Philadelphia, Pennsylvania
  “Managing the Adverse Event Profile of EGFR Inhibitors”
• 2008 American Society of Clinical Oncology^® Annual Meeting
  May 30 in Chicago, Illinois
  “Bench to Bedside: Innovative Approaches to Hematologic Malignancies”
• 2008 American Society of Clinical Oncology^® Annual Meeting
  May 30 in Chicago, Illinois
  “Contemporary Strategies for Abrogating Immunologic Tolerance to Melanoma”

The FDA has assigned priority review status to the supplemental new drug application (sNDA) for sanofi-aventis’ oxaliplatin (Eloxatin^®) for the treatment of patients with colorectal cancer. In the sNDA, the company wants to include the 6-year analysis from the MOSAIC trial in the drug’s prescribing information. The trial data contain rates for 6-year OS and 5-year disease-free survival (DFS) in patients with stage III colon cancer treated with either an oxaliplatin-based regimen or standard infusion chemotherapy alone following surgery to remove the primary tumor (adjuvant therapy). The group receiving an oxalipatin-based regimen had a significant 20% reduction in the risk of dying compared to the control group and the DFS was improved by 22%.

GTx Inc.’s toremifene citrate, an investigational therapy to treat the side effects of androgen deprivation therapy (ADT) in patients with advanced prostate cancer, has met several endpoints in a late-stage trial. The 2-year double-blind, placebo-controlled trial randomized 1,389 men receiving ADT in the US and Mexico to receive toremifene citrate 80 mg or placebo. Trial results demonstrated that toremifene reduced vertebral fractures and met other main goals, including improvement of bone mineral density, cholesterol-related profiles, and gynecomastia. Based on the positive results, GTx plans to file a new drug application (NDA) with the FDA this summer.

Save the Date

Dates have been announced for Oncology Highlights, the premier venue for many of the world’s top oncologists and hematologists to summarize and interpret the most clinically significant data released from the American Society of Clinical Oncology’s (ASCO) Annual Meeting. In addition to question and answer periods, the audience will be able to interact by way of an audience response system.  Registration opens May 1^st!

July 12  Dallas, TX
July 19  San Francisco, CA
July 19  New York, NY
July 26  Chicago, IL
August 2  New York, NY
August 9  Aventura, FL

The next issue of OncoFacts™ will be in April 2008 and then monthly throughout the year.

OncoFacts Editor:

Jim Jones, MD

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

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