2014 ASCO Annual Meeting Review
Michael Newton, PharmD BCOP
Clinical Associate Professor
West Virginia University School of Pharmacy Clinical Specialist, Ambulatory Oncology West Virginia University Healthcare
The American Society of Clinical Oncology (ASCO) held its 50th Annual Meeting in Chicago, IL, May 31–June 3, 2014. The official theme of this year’s meeting was “Science and Society” and focused on opportunities for the community of clinicians and researchers to lead society in the quest for knowledge and insight as it pertains to cancer. The meeting certainly delivered on its theme, presenting a diverse array of trial results that will affect practice and guide future research. The following is a summary of a few of the important findings presented.
LBA1: Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer Patients
The combined results of two phase 3 trials, Tamoxifen and Exemeastane Trial (TEXT) and the Suppression of Ovarian Function Trial (SOFT), were presented during the plenary session. The trials compared 5 years of adjuvant exemestane plus ovarian suppression with tamoxifen plus estrogen suppression in 4,690 premenopausal women. The method of ovarian suppression was based on physician and patient preference and included triptorelin, oophorectomy, or ovarian irradiation. Disease-free survival at 5 years was superior in the exemestane group (91.1% versus 87.3%; hazard ratio [HR] for disease recurrence, second invasive cancer, or death = 0.72; 95% confidence interval [CI]: 0.60–0.85; p < .001).
LBA4: Disappointing Final Results of ALTTO Trial
This trial examined the benefit of adding lapatinib to trastuzumab either concurrently or sequentially, in the adjuvant treatment of HER2-positive breast cancer. Unfortunately, lapatinib did not increase disease-free survival compared with trastuzumab alone. These results were disappointing and unexpected given the significantly increased pathologic complete response rates reported from the addition of lapatinib to trastuzumab in the neoadjuvant setting (reported previously in the NeoALTTO trial, available in Lancet 2012;379:633-640).
LBA505: Prevention of Early Menopause Study (POEMS)
In this trial, women younger than 50 years with stage I, II, or IIIa ER/ PR-negative breast cancer were randomized to receive a cyclophosphamide-based adjuvant chemotherapy regimen with or without goserelin at a dose of 3.6 mg monthly, starting 1 week before chemotherapy. The primary endpoint was rate of premature ovarian failure (POF). Rate of POF was 22% in the standard arm and 8% in the goserelin arm (OR = 0.30, 95% CI: 0.10–0.87; p = .03). A secondary endpoint in this trial was rate of pregnancy. Roughly the same proportion of women in each arm reported that they attempted to conceive after treatment, and more women in the goserelin arm were able to become pregnant (21% versus 11%; OR = 2.45; p = .03).
LBA 9500: Zoledronic Acid Every 4 Weeks Versus Every 12 Weeks
In this prospective, randomized, double-blind trial, women with bone metastases from breast cancer who previously received approximately 1 year of monthly intravenous (IV) bisphosphonate (either zoledronic acid or pamidronate) were randomized to receive either zoledronic acid 4 mg intravenously every 4 weeks or every 12 weeks for 1 year. There were no differences between the arms in rates of skeletal-related events. Treatment-related adverse events were similar in both arms; however, there were two cases of osteonecrosis of the jaw in the every-4-week arm and none in the every-12-week arm.
Abstracts 8002 and 8003: Important Data for Patients with ALK Translocation Positive NSCLC
In abstract 8002, the PROFILE 1014 trial confirmed that in first-line treatment, crizotinib is superior to doublet chemotherapy in patients with advanced anaplastic lymphoma kinase (ALK)-positive, nonsquamous non-small cell lung cancer (NSCLC). The study met its primary objective of prolongation of progression-free survival (PFS), demonstrating superiority of crizotinib over chemotherapy (median PFS 10.9 versus 7.0 mo; HR = 0.454; 95% CI: 0.346−0.596; p < .0001). The overall response rate was also significantly higher with crizotinib (74% versus 45%; p < .0001). Overall survival data are not yet mature, however, overall survival is a secondary endpoint, and the trial has a crossover design.
Abstract 8003 reported results from the expansion phase of the ASCEND-1 trial of ceritinib (formerly LDK378) in ALK-positive lung cancer patients (phase 1 results available in NEJM 2014;370:1189-1197). In the 180 patients evaluated, overall response rate was 60%. Of the 121 patients who had previously received crizotinib, the response rate was 55.4%, with a median duration of response of 7.4 months. Ceritinib gained U.S. Food and Drug Administration (FDA) approval in April 2014 for treatment of ALK-positive lung cancer patients previously treated with crizotinib.
Abstract 8005: Erlotinib Plus Bevacizumab Versus Erlotinib Alone as First-Line Treatment for Advanced EGFR Mutation-Positive Nonsquamous NSCLC
This open-label trial randomized epidermal growth factor receptor (EGFR)–positive advanced or metastatic NSCLC patients to receive either erlotinib 150 mg by mouth daily or the same dose of erlotinib combined with bevacizumab 15 mg/ kg intravenously every 3 weeks. Progression-free survival was superior in the combination arm (16.0 months versus 9.7 months; HR, 0.54; 95% CI: 0.36–0.79; log-rank p = .0015). Response rates were similar, and adverse events were considered manageable in the combination arm.
LBA2: Impact on Overall Survival with Chemohormonal Therapy Versus Hormonal Therapy for Hormone-Sensitive Newly Metastatic Prostate Cancer: An ECOG-Led Phase 3, Randomized Trial
In this potentially practice-changing trial, 790 men with metastatic hormone-sensitive prostate cancer who received androgen-deprivation therapy (ADT) were randomized to ADT alone or ADT plus docetaxel 75 mg/m2 every 3 weeks for six cycles. Patients receiving docetaxel were required to start chemotherapy within 4 months of initiation of ADT. The primary endpoint of overall survival demonstrated superiority of combination chemohormonal therapy compared with ADT alone (median overall survival was 52.7 months versus 42.3 months; p = .0006). Of note, patients who progressed on the ADT-alone arm were eventually given docetaxel as per the current standard of care. Survival benefit was most profound in men with high-volume disease, with an increase in survival of 17 months. Data are currently insufficient to determine whether men with low-volume disease would benefit from this strategy.
LBA3: CALGB/SWOG 80405 Phase 3 Trial of FolFIRI or FolFOX with Bevacizumab or Cetuximab for Patients with KRAS Wild-Type Untreated Metastatic Colorectal Cancer
Results from the CALGB/ SWOG 80405 trial (LBA3) found that for first-line treatment of metastatic colorectal cancer in patients who are KRAS wild-type, overall survival for cetuximab plus chemotherapy is equivalent to bevacizumab plus chemotherapy (approximately 29 months in both arms). It should be noted that the selection of FolFOX or FolFIRI as the first-line chemotherapy backbone was at the discretion of the treating physician and that there was a strong preference for FolFOX (73.4%). This is particularly important because previous studies have suggested that the cetuximab plus FolFOX combination may be inferior to FolFOX alone in the first-line setting.
As usual, the ASCO Annual Meeting presented clinicians with an enormous amount of data to digest. While not discussed in this review, excitement about immunotherapy continued to grow at ASCO 2014. We will likely see the first of the PD-1 inhibitors approved in late 2014, and I encourage readers to review abstracts related to these agents in melanoma and in other disease states. Also of note, value in cancer care was a recurrent theme at the meeting, which is not surprising given ASCO’s recent launch of the strategic Value in Cancer Care Initiative.