BY CHARLES L. LOPRINZI, MD
Regis Professor of Breast Cancer Research
Division of Medical Oncology
ASCO 2014 provided a number of interesting symptom-intervention abstracts -- some of which will affect clinical practice.
Two abstracts were presented at the patient care oral session regarding bone health. One of them (Abstract LBA9500) looked at the use of zoledronate given every four weeks versus every 12 weeks in patients who previously had at least nine monthly doses of zoledronate. These data revealed that there was a similar incidence in skeletal-related events in the patients in both arms. Adverse events were also very similar in both arms, although there were a few more patients who stopped zoledronate due to adverse events in the four-week arm, including two cases of jaw osteonecrosis in that arm.
These data confirm previous data from the ZOOM trial, which showed similar results with women who received treatment every four weeks vs. every 12 weeks. The combined results of both of these trials better establish zoledronate therapy every 12 weeks, as opposed to every four weeks, following a year of monthly zoledronate therapy.
While this will be a practice change for many oncologists, many others have been treating at three-month intervals for the second year, already. Of note, data from another randomized trial (CALGB 70604) looking at four-week vs. 12-week administration of zoledronate for two years, starting with zoledronate initiation, will, hopefully, be presented in 2015.
Another bone health related abstract (Abstract 9501) compared denosumab with zoledronate, looking at subgroup analyses of patients from three previous randomized trials. These presented confirmed data from previous reports of these studies, looking at all patients, as opposed to subgroups. In concert with the previous reports revealing that the time to skeletal-related events was statistically better in patients receiving denosumab, compared with zoledronate, the current report revealed that these denosumab-related benefits were seen across all subsets of patients.
Acknowledging this denosumab-related benefit, the discussant of this abstract, Dr. Thomas Smith, noted that the cost of denosumab is considerably higher than that of zoledronate, that there is no known difference in survival between patients receiving either of these agents, and that the most recent ASCO guidelines, published in 2011, did not recommend a preference for one bone-modifying agent over the other.
Two abstracts, also presented at the oral patient care session, discussed cardiac issues. One of these (Abstract 9504) looked at the long-term risk of heart failure in patients who had received adjuvant trastuzumab. While the risk of heart failure was higher in the first one and a half years in patients receiving trastuzumab (2.6% vs. 5.3% incidence), after one and a half years the incidence was similar.
A study looking at heart disease issues in patients with Hodgkin’s disease (Abstract 9505) provided further confirmatory data that these patients are at a high risk for cardiac events for years to decades, especially if they had received mediastinal radiation therapy.
Another oral session presented an abstract evaluating intravaginal dehydroepiandrosterone (DHEA) for improving vaginal symptoms in female cancer survivors (Abstract 9507). This randomized, placebo-controlled, three-arm study, evaluating two doses of DHEA, reported that there was an improvement in vaginal function and sexuality, with DHEA compared with a vaginal moisturizer alone. The therapy was well tolerated although there was some mild hirsutism and a minimal increase in acne with DHEA. While DHEA did increase serum DHEA and testosterone concentrations, it did not substantially increase estrogen serum concentrations, particularly in patients receiving aromatase inhibitors. These data support the use of this product for patients with vaginal dryness in whom topical estrogen would be contraindicated.
Another study (Abstract 9510) evaluated a standardized exercise program which was demonstrated to reduce psychological distress and improve inflammatory cytokines of distress among men with prostate cancer, further supporting the efficacy of exercise in patients with cancer as tolerated.
Regarding chemotherapy-induced peripheral neuropathy (CIPN), a pilot trial reported that Scrambler therapy, an electro-cutaneous treatment, appeared to decrease neuropathy in patients with established severe CIPN, more than what would have been expected with a placebo alone (Abstract 9622). This supports that this treatment approach should be evaluated in a placebo-controlled trial manner.
An interesting abstract evaluated the use of pegfilgrastim at various times following the administration of breast cancer therapy (both anthracycline/cyclophosphamide treatment and paclitaxel treatment) (Abstract 9632). Cohorts of patients received the pegfilgrastim 24 vs. 72 vs. 96 hours after chemotherapy. From serial blood counts being obtained after this was administered, it was noted that white blood cell counts were extraordinarily high one day after the pegfilgrastim in the patients who received such 24 hours following chemotherapy (62.5 x 103 units). Administration of pegfilgrastim 72 hours after chemotherapy was associated with less substantial neutrophil counts after pegfilgrastim; no differences in chemotherapy delays were observed in patients treated with pegfilgrastim 24 vs. 72 hours following chemotherapy. These authors proposed that it would be better to take pegfilgrastim 72 hours following chemotherapy. These data do support that pegfilgrastim can effectively be used 72 hours following chemotherapy.
Lastly, a randomized study in hormone receptor negative breast cancer involving 257 patients (Abstract LBA505) studied the use of an LHRH analog started prior to adjuvant chemotherapy in premenopausal women who wished to maintain fertility. Patients receiving the LHRH analog were less likely to have premature ovarian failure (8% vs. 22%), had more pregnancies (22 vs. 13), and, unexpectedly, had improved survivals (HR 0.04; p = 0.04).