More than 30,000 attendees from all over the world are expected to attend the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) on May 30-June 3, 2014, in Chicago. In the pre-meeting presscast, five studies were selected and highlights ranged from resource utilization and low-dose computed tomography screening for lung cancer to novel therapies targeted to specific abnormalities.
Low-dose Computed Tomography Screening in NSCLC
A study based on mathematical modeling projected the 5-year outcomes of implementing the United States Preventive Services Task Force (USPSTF) recommendation to screen patients at high-risk of lung cancer with low-dose computed tomography (LDCT) in the Medicare population. Looking at an expected-use scenario (50% of patients offered screening undergo screening), the study showed that LDCT as recommended would detect 54,900 more cases of lung cancer over 5 years compared with screening, and the majority of these cancers would be stage I.
In fact, this program would increase the proportion of early-stage diagnosis from 15% to 33%. This effort would entail use of 11.2 million more scans, and cost $9.3 billion more in expenditures (primarily on LDCT scans). This boils down to a $3 per month premium increase per Medicare member, explained lead author Joshua A. Roth, PhD, MHA, a postdoctoral research fellow at Fred Hutchinson Cancer Research Center in Seattle, WA.
Dr. Roth said that this study was not designed to look at QALY or value of LDCT, but as a projection of what to expect in terms of resource utilization so that Medicare and other healthcare systems can plan accordingly if the USPSTF recommendation is implemented.
Obesity and Breast Cancer
A study showed that obesity (i.e., body mass index [BMI] ≥30 kg/m2) increases breast cancer mortality only in women with pre-menopausal ER+ disease, but not in post-menopausal ER+ disease or ER-negative breast cancer. The study included more than 80,000 patients enrolled in 70 trials. Data were collected on BMI, ER status, menopausal status, breast cancer recurrence, and death. Obese women with early breast cancer were compared with women of normal weight. Obesity was an independent factor predicting breast cancer mortality in 20,000 premenopausal women with ER+ breast cancer (relative risk ratio of 1.34), while obesity had little effect on breast cancer mortality in 40,000 post-menopausal women with ER+ breast cancer or in the 20,000 women with ER-negative breast cancer. The rate of breast cancer mortality was 21.5% in obese women with premenopausal ER+ breast cancer versus 16.6% in women of normal weight, amounting to a 10-year difference of about 5%, said lead author Hongchao Pan, PhD, a researcher at the University of Oxford, U.K.
“This is yet another study showing the detrimental effects of obesity in cancer. Overall, obesity is a negative prognostic feature and we need to attend to this,” said Clifford A. Hudis, MD, ASCO president.
PSA Relapse in Prostate Cancer
A large observational study included 14,300 men diagnosed with biopsy-proven prostate cancer who completed curative surgery or radiation; of these, 2012 men developed PSA relapse (rising PSA but asymptomatic) and were treated with immediate androgen deprivation therapy (ADT, within 3 months of rising PSA) or delayed ADT (at least 2 years after PSA relapse or when they presented with metastasis, symptoms, or short doubling of PSA time). In the study, PSA relapse was defined as ≥.02 ng/ml or 3 rising PSA measurements in asymptomatic patients with no evidence of metastatic disease.
Median time from primary treatment to PSA relapse was 27 months. After relapse, patients were followed for 41 months. The estimated 5-year overall survival was 85.1% for the immediate ADT group and 87.2% in the delayed ADT group. Ten-year OS was identical in both groups: 71.6%.
“Survival was similar for prostate cancer mortality and all-cause mortality,” stated lead author Xabier Garcia-Albeniz, MD, a research associate at Harvard University School of Public Health in Boston, MA.
This study provides some fodder for discussions with patients, some of whom may not want to go on ADT because of the side effects. Dr. Garcia-Albeniz said results will not change clinical practice. For that to happen, results of an ongoing randomized Phase III trial comparing the two strategies will be needed.
Mutation Resistance in NSCLC
A phase I study found that a novel selective EGFR tyrosine kinase inhibitor (TKI) known as AZD9191 appears to overcome the mutation T790M responsible for resistance to previous TKI therapy in patients with non-small cell lung cancer (NSCLC) who harbor that mutation. The study did not identify a dose-limiting toxicity or a maximal tolerated dose for AZD9191.
This preliminary study included 199 patients with advanced NSCLC and EGFR mutations who progressed on 1 or more standard EGFR therapies. Overall 51% of patients experienced tumor shrinkage; response was more robust in those with the T790M mutation (64% versus 23% in those who were T790M-negative).
“Currently there is no appropriate therapy for these patients. This drug warrants further study,” said lead author Pasi A. Jänne, MD, PhD, Dana-Farber Cancer Institute and Harvard Medical School in Boston.
Pigmented Villonodular Synovitis
A small phase I study showed that a novel oral therapy PLX3397 targeted to the colony-stimulating factor 1 (CSF1) receptor and other molecular targets appears to improve the symptoms and functionality of patients with a rare neoplastic joint disorder called pigmented villonodular synovitis (PVNS). About 600 patients are diagnosed with PVNS each year in the U.S. and the disease is characterized by collagen scarring, bone destruction, and repeat joint bleeds. It is associated with functional impairment and disability. Some patients may even need limb amputation. The study enrolled 23 patients with PVNS, and 11 of 14 evaluable patients showed rapid, dramatic, sustained responses to PLX3397. PLX3397 was well tolerated and patients achieved marked clinical improvement.
“These results are a shining example of how patients can experience a meaningful clinical benefit when we are able to match the right treatment with the right target,” said lead author William D. Tap, MD, Memorial Sloan-Kettering Cancer Center in New York City. A Phase III trial of this compound is planned.
by Alice Goodman