By Alice Goodman
May 19, 2011 — Five newsworthy abstracts to be presented at the 2011 annual meeting of ASCO were singled out for attention during a pre-meeting press cast. The topics included the safety of current cervical cancer screening guidelines, the first genetic biomarker for taxane-induced neuropathy, PARP inhibitor maintenance therapy for ovarian cancer, and a novel agent with dual targets showing impressive activity in several tumor types and eradicating bone metastases.
Co-Screening with HPV and Pap Tests
The first large-scale study of co-testing for human papilloma virus (HPV) and Pap smear to detect cervical cancer in women age 30 and older found that the combination of both tests were better than the Pap test alone and that a 3-year screening interval was safe for women who were HPV-negative and had a normal Pap test. Although current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and American Cancer Society (ACS) recommend co-testing with a 3-year interval between screenings for women with no abnormalities on either test, this standard has not gained widespread adoption in clinical practice, perhaps based on fears that it is not safe. The study, based on more than 330,000 women in the Kaiser-Permanente Northern California database who were co-tested [with both tests] between 2003 and 2005 and followed until 2009, should provide assurance that the guidelines are safe. The study found that HPV testing was more accurate than Pap testing in determining cervical cancer risk, but lead author Hormuzd Katki, PhD, National Cancer Institute, said that the Pap test should not be thrown out. Pap testing was especially useful in women who were HPV-positive, identifying another 6% of potential cancers in that subgroup. Katki also emphasized that women with an HPV-positive test should be followed rigorously and seen at 1-year intervals.
Genetic Biomarker for Taxane-Induced Neuropathy
A genome-wide association study (GWAS) has identified the first genetic biomarkers for taxane-induced peripheral neuropathy, an uncomfortable and compromising side effect that occurs in about 30% of all patients treated with taxane-based chemotherapy. This finding may allow the development of a simple blood test to identify patients at high risk for neuropathy. Lead author Bryan P. Schneider, MD, Indiana University Melvin and Bren Simon Cancer Center, said: “If these findings can be replicated, physicians may be able to better counsel patients about what to expect and consider alternate drugs or schedules.” GWAS was conducted in 2204 participants in a randomized controlled trail (Eastern Cooperative Oncology Group 5103) in which all patients received taxane-based chemotherapy. At a median follow-up of 15 months, genetic subgroups more likely to develop neuropathy were identified. Clinical factors that predicted neuropathy included older age and African-American race. The strongest association with neuropathy was observed for a single nucleotide polymorphism (SNP) in the RWDD3 gene. Patients with no SNP in this gene had a 27% likelihood of developing neuropathy; those with 1 normal nucleotide and 1 copy of the SNP had 40% likelihood, and those with two copies of the SNP had 60% likelihood of developing neuropathy. Further analysis of SNP groups is under way.
Olaparib Maintenance Therapy of Relapsed Ovarian Cancer
Following treatment for relapsed serous ovarian cancer, maintenance therapy with the oral PARP inhibitor olaparib improved progression-free survival (PFS) by about 4 months. This is the first randomized trial to demonstrate a benefit for maintenance therapy for recurrent ovarian cancer, and the first randomized trial to show a benefit for a drug in platinum-sensitive, high-risk, serous ovarian cancer, said lead author Jonathan Lederman, MD, professor of Medical Oncology at UCL Cancer Institute, University College, London, UK. The multicenter, international randomized trail randomized 265 women with high-grade serious ovarian cancer to receive maintenance therapy with olaparib or placebo. All patients enrolled in the trial had a complete or partial response to platinum-based chemotherapy for relapsed ovarian cancer. Progression-free survival (PFS) was a median of 8.4 months for those in the olaparib group versus 4.8 months in the placebo group. Overall survival data are not yet available. At the time results were presented, 50% in the olaparib group had not relapsed and were still being treated compared with only 16% of the placebo group. The most common adverse events associated with olaparib were nausea, fatigue, vomiting and anemia. Studies are under way to evaluate olaparib as routine therapy for ovarian cancer, he said. PARP inhibitors are being studied in Phase 2 and 3 trials either alone or in combination with other chemotherapies for both breast and ovarian cancer, he noted.
Cabozantinib (XL184) for Solid Tumors and Bone Metastases
Patients with various types of advanced cancer — particularly those with ovarian and non-hepatocellular liver cancer — had a strong response to cabozantinib in a Phase 2 trial. Moreover, the drug fully or partially eliminated bone metastases in patients with breast and prostate cancer, and melanoma. Cabozantinib is an oral inhibitor of VEGFR2 and MET (involved in cell survival). The randomized discontinuation study included 398 patents (39% with bone metastasis at baseline) treated with cabozantinib for 12 weeks. Lead author Michael S. Gordon, MD, a medical oncologist at Pinnacle Oncology Hematology in Scottsdale, AZ, said that the study design allowed patients with partial response (PR) at 12 weeks to remain on treatment with the drug, while those with stable disease were randomized to cabozantinib or placebo, and those with progressive disease went off study.
“This novel type of clinical trial design is a quicker way to evaluate the disease-stabilizing activity of growth-inhibitory agents like cabozantinib, compared with the traditional randomized trial with an experimental and placebo arm,” he explained.
At week 12, the highest rates of disease control (i.e., stable disease and partial response) were 76% in those with non-hepatocellular cancer, 71% for prostate cancer, and 58% for ovarian cancer. Fifty-nine of 68 patients with bone metastases had either partial or complete disappearance of cancerous lesions on bone scans, along with significant relief of pain and other symptoms. Dr. Gordon said that the effects of bone metastases were unexpected and “unprecedented.” Side effects include fatigue (9%), hand-foot syndrome (8%), and hypertension requiring anti-hypertensive treatment (5%). The cohorts with castration-resistant prostate cancer and ovarian cancer have been expanded to include about 150 patients in each group, and results in these groups will be presented at the upcoming Annual Meeting of ASCO. Cabozantinib is also being studied in other tumor types, including a pivotal trial in medullary thyroid cancer.
Smoking, Alcohol Use, Exercise and Risk of Cancer
According to an analysis of the large, prospective NSABP Breast Cancer Prevention trial originally designed to compare tamoxifen versus placebo in 13,000 healthy women at high risk of breast cancer, the risks of invasive breast, lung, and colon cancers were 34% to 60% higher in women who smoked cigarettes over 15 to 35 years compared with women who did not smoke or smoked for shorter periods of time. The study also found a 70% increased risk of endometrial cancer associated with low levels of physical activity. Contrary to some other studies, however, alcohol use did not increase the risk of invasive cancers, and moderate alcohol consumption (up to 1 drink per day) reduced the risk of colon cancer by 60% compared with non-drinkers. This study suggests that smoking is even more risky for women at risk of breast cancer from family history or other factors, said lead author Stephanie Land, PhD, and Research Associate Professor in the Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, PA. Over the course of the study, 395 women developed breast cancer, 66 developed non-small-cell lung cancer, 35 developed colon cancer, and 74 developed endometrial cancer.