Recent ASCO Research Articles

Novel therapies in breast cancer: what is new from ASCO 2008.

IntroductionBreast cancer is the most common female cancer and the second most common cause of female cancer-related deaths in the United States. World-wide, more than one million women will be diagnosed with breast cancer annually. In 2007, more than 175,000 women were diagnosed with breast cancer in the United States. However, deaths due to breast cancer have decreased in the recent years in part because of improved screening techniques, surgical interventions, understanding of the pathogenesis of the disease, and utilization of traditional chemotherapies in a more efficacious manner. One of the more exciting areas of improvement in the treatment of breast cancer is the entrance of novel therapies now available to oncologists. In the field of cancer therapeutics, the area of targeted and biologic therapies has been progressing at a rapid rate, particularly in the treatment of breast cancer.Since the advent of imatinib for the successful treatment of chronic myelogenous leukemia in the 2001, clinicians have been searching for comparable therapies that could be as efficacious and as tolerable. In order for targeted therapies to be effective, the agent must be able to inhibit critical regulatory pathways which promote tumor cell growth and proliferation. The targets must be identifiable, quantifiable and capable of being interrupted.In the field of breast cancer, two advances in targeted therapy have led to great strides in the understanding and treatment of breast cancer, namely hormonal therapy for estrogen positive receptor breast cancer and antibodies directed towards the inhibition of human epidermal growth factor receptor (HER)2. These advances have revolutionized the understanding and the treatment strategies for breast cancer. Building upon these successes, a host of novel agents are currently being investigated and used in clinical trials that will hopefully prove to be as fruitful. This review will focus on novel therapies in the field of breast cancer with a focus on metastatic breast cancer (MBC) and updates from the recent annual ASCO meeting and contains a summary of the results.

Characterizing cancer research in Brazil through bibliometric analysis of abstracts from the ASCO meetings 2001–2005

17561 Background: The science and practice of cancer medicine in Brazil currently display features of both developing and developed countries. Cancer research is increasing in Brazil, and several recent large, international, industry-sponsored trials have included a substantial number of Brazilian patients. However, it is unclear to what extent there is proportional increase in research originated in Brazil. We approached this question using a bibliometric analysis of Brazilian abstracts from recent ASCO Annual Meetings. Methods: We conducted a manual search of the 16,925 abstracts published in the Program Proceedings and late-breaking abstracts booklets for 2001 through 2005. We defined as Brazilian an abstract for which at least two-thirds of institutions were from Brazil. We tabulated study characteristics and searched PubMed and Lilacs databases for their full publications, using first and last authors’ names. Results: We located 154 Brazilian studies (0.90% of total; 95% CI 0.77% - 1.07%), of which 76.0% were categorized as clinical investigation, 14.9% as basic research, and 9.1% as epidemiologic research. In clinical investigation, the most frequent study types were retrospective (N=43) and phase II trials (N=37). The most frequent topic categories were tumor biology (N=27), patient care (N=22), breast (N=19), lung and gastrointestinal cancer (N=13 each). There was a significant increase in the proportion of Brazilian abstracts from 2001 to 2005 (P=0.011 for trend). Only 31.8% of the studies were presented at the meeting, usually as posters, with the other 68.2% appearing as “publication only”. There was no significant trend in the proportion of “publication only” abstracts (P=0.407). After a median follow up of 35 months, only 16.9% of studies were published (median time to publication, 13.5 months). Univariate Kaplan-Meier analyses showed no significant predictors of publication, although “publication only” abstracts were less likely to be published in full (P=0.059). Conclusions: Our study provides empiric evidence for an increase in research that is originated in Brazil. However, it also suggests that the quality of such research needs to improved, and that efforts are also needed in order to increase the rate of full publication. No significant financial relationships to disclose.

Fertility preservation in gynecologic cancers

This review focuses on the current options for fertility preservation in young women facing the risk of premature ovarian failure and infertility as a sequel to the treatment of gynecologic cancer. There is a wide range of options to preserve fertility. Embryo freezing is the most established method and the success rate of in-vitro fertilization using frozen-thawed embryos now approaches that of using fresh embryos. Success rates with oocyte cryopreservation are on the rise and begin to approach that of embryo freezing. Exposure to high levels of estrogen during ovarian stimulation can be minimized by utilizing aromatase inhibitors in women with estrogen-sensitive cancers undergoing embryo or oocyte cryopreservation. Ovarian-tissue cryopreservation is used to preserve fertility in children and in patients with time restraints; however, the number of reported cases is very small. Likewise, in-vitro maturation and xenografting are experimental and their potential to preserve fertility remains to be determined. A number of fertility-preservation techniques have been developed and many others are in the experimental stages. Consistent with recent ASCO clinical guidelines, all young individuals with gynecologic cancer should be counseled about the available fertility preservation techniques.

Assessment of Clinical Outcomes Following Erythropoietic Intervention at a Hemoglobin Concentration above 10 g/dL: A Comprehensive Review of Recent Literature.

Current practice guidelines for the management of chemotherapy-induced anemia (CIA) recommend initiating erythropoietic intervention at hemoglobin (Hb) ≤ 10 g/dL (American Society of Hematology [ASH]/American Society of Clinical Oncology [ASCO]), or at Hb ≤ 11 g/dL (National Comprehensive Cancer Network [NCCN]). This comprehensive literature review summarizes published findings of randomized controlled trials (RCTs) that evaluated the effects of initiating erythropoietic treatment at Hb > 10 g/dL on transfusion incidence, Hb concentration, and/or patient-reported outcomes, relative to control. A search of the Medline database and conference proceedings (ASH and ASCO) from 1999 to 15 June 2004 was conducted to identify RCTs that evaluated the ability of erythropoietic agents to prevent the onset or worsening of CIA. Mantel-Haenszel weighted summary estimates of the relative risk were calculated to evaluate outcomes in patients treated with epoetin alfa compared to control patients. Using predefined selection criteria, 4 full-length papers (summarized in the table) and 5 abstracts (Chang ASCO 2003; Savonije ASCO 2004; Straus ASH 2003; Crawford ASCO 2003; Rearden ASCO 2004) were identified and reviewed. Epoetin alfa effectively decreased transfusion incidence and the percentage of patients with Hb decline to < 10 g/dL vs no treatment in 4 RCTs reported from 1997 onward (table). The estimated summary relative risk (95% CI) for transfusion and Hb < 10 g/dL are 0.39 (0.26–0.57; P < 0.0001) and 0.48 (0.25–0.89), respectively. These results were consistent with early results reported in 2 additional RCTs (Chang ASCO 2003; Savonije ASCO 2004), which were of similar design. The preliminary results of 3 additional RCTs that directly compared outcomes following early (Hb > 10 g/dL) and late (Hb ≤ 10 g/dL) erythropoietic intervention were presented at recent ASH and ASCO conferences (Straus ASH 2003; Crawford ASCO 2003; Rearden ASCO 2004). All 3 studies provided evidence of lower incidence of transfusion, higher Hb levels over time, and/or better patient-reported outcomes among patients treated early compared with those treated late. The results of the studies examined demonstrate the clinical benefits of initiating erythropoietic treatment at a Hb concentration > 10 g/dL, with respect to reducing transfusion requirements and improving Hb levels, in patients with cancer undergoing chemotherapy. Although the findings are preliminary and have yet to appear in peer-reviewed journals, the comparative RCTs of early vs late intervention point to a trend in which patients who received erythropoietic treatment early experienced better clinical outcomes overall than patients treated late.Bamias 2003Thatcher 1999ten Bokkel Huinink 1998Del Mastro 1997Hb Eligibility Criterion (g/dL)≤13≥10.5< 13≥ 12Baseline Hb (g/dL)11.5 (E)13.7 (E)12.0 (E)13.0 (E)11.5 (C)13.4 (C)11.8 (C)13.1 (C)Transfusion Incidence (%)15* (E)45* (E)4**(E)0 (E)33 (C)59 (C)39 (C)6 (C)% Patients with Hb < 10 g/dLª17*** (E)48* (E)18* (E)0*** (E)46 (C)66 (C)50 (C)52 (C)Dosing Regimen10,000 U TIW150 U/kg TIW150 U/kg TIW150 U/kg TIWNo treatment (control)No treatment (control)No treatment (control)No treatment (control)E=epoetin alfa; C=no treatment control; reported p < 0.05 (*), 0.01 (**), 0.001 (***) vs control. ªHb ≤10 g/dL in Del Mastro study