At the 18th Annual Conference of the National Comprehensive Cancer Network (NCCN), experts presented the latest updates to the NCCN Clinical Practice Guidelines in Oncology. The conference also featured two roundtable discussions that covered topics including cancer treatment costs, disparities in the quality and value of oncology care, the implications of big data in the field of oncology, and personalized cancer care. Here are perspectives from key opinion leaders on the NCCN Guidelines Updates.
Robert J. Morgan, MD
City of Hope Comprehensive Cancer Center
“There are no major changes to the ovarian cancer guidelines this year. The biggest management change may occur in the coming year due to our improved understanding of the role of bevacizumab in treating recurrent epithelial ovarian cancer. The publication of the OCEANS trial resulted in an addition to the guidelines of the regimen of carboplatin/gemcitabine/ bevacizumab to the list of acceptable recurrence therapies. We’ll have more clarity next year when the results of the AURELIA trial in platinum-resistant disease are published. In this trial, a progression-free survival benefit in patients with platinum-resistant disease has been reported.”
Bevacizumab (Avastin) currently carries a category 2B recommendation in recurrence therapy, but the results of the AURELIA trial may have an impact on clinical guidelines going forward. In frontline treatment, bevacizumab is a category 3 recommendation.
The new guidelines refine the guidance for physicians following patients with less-common histopathologies, including sex cord stromal tumors and germ cell tumors. Germ cell tumors, which are often seen in young people, can be exquisitely sensitive to chemotherapy. The 2013 edition of the guidelines adds published surveillance strategies for patients postchemotherapy, including a suggested follow-up regimen after completion of treatment during and after the first 5 years that specifies recommendations for performing radiographic imaging and serum tumor marker tests, for example. The recommendations for follow-up for germ cell tumors include serum tumor markers for the first 2 years after treatment is completed. They can then be omitted because virtually all of these tumors recur within that time frame if they are destined to recur. However, sex cord stromal tumors must be followed more aggressively, even following the first 5 years, due to their tendency to exhibit late recurrences.
Surgical treatment recommendations have also been updated. Appendectomy has been added to other reasonable surgical options in staging and debulking for both early- and late-stage disease as a strategy to optimize cytoreduction in aggressive gynecologic cancers. The definition of optimal surgical debulking is evolving.
Leonard Saltz, MD
Memorial Sloan-Kettering Cancer Center
“For the treatment of metastatic disease, two new drugs [ziv-aflibercept and regorafenib] not previously available to colorectal cancer patients have been incorporated into the guidelines, and there is one change of substance in how we use existing drugs. These three therapies all involve to some degree targeting [VEGF], a protein that stimulates production of new blood vessels, and all produced modest benefits. The gains we see are statistically
significant, but it’s open to discussion whether they are clinically
Regorafenib (Stivarga) was approved by the FDA following an expedited review as a single-agent, last-line salvage therapy for patients with good performance status whose cancer has progressed after treatment with all other standard therapies.
Bevacizumab (Avastin) is now recommended for use as a second-line therapy in combination with chemotherapy (fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin) for the treatment of patients whose disease has progressed after a first-line program with a bevacizumab-containing regimen. Previously, the guidelines supported its use in first- or second-line therapy, but did not support its use in both first- and second-line treatments.
Ziv-aflibercept (Zaltrap) was added as a second-line treatment used in combination with FOLFIRI (5-fluorouracil, leucovorin, and irinotecan) for patients whose cancer is resistant to or has progressed following treatment with a first-line oxaliplatin-containing regimen.
While the guidelines were changed to allow for either second-line use of bevacizumab or second-line use of ziv-aflibercept, it’s important for clinicians to understand that the data do not support using both—meaning they do not support using second-line bevacizumab and then second-line ziv-aflibercept with the same chemotherapy. Second-line use of ziv-aflibercept is an alternative option to second-line bevacizumab, but not a new treatment paradigm.
For earlier-stage patients, there is one important change to the guidelines: The guidelines allow for use of oxaliplatin in patients with stage II disease with higher risk, but this is no longer a preferred option. Instead, the guidelines now state that good-risk stage II patients should not receive oxaliplatin.
Clifford A. Hudis, MD
Memorial Sloan-Kettering Cancer Center
“A key change in the guidelines in HER2-positive breast cancer is the incorporation of pertuzumab [Perjeta], the second monoclonal antibody targeting this receptor. A related and recent addition is ado-trastuzumab emtansine [Kadcyla, or T-DM1] for patients with tumors refractory to conventional trastuzumab. “Outside of HER2-positive disease, the use of the first available agent targeting the PI3 kinase pathway, specifically the mammalian target of rapamycin (mTOR), represents a new approach to the palliative use of aromatase inhibitors. All of these changes are exciting as they suggest that ongoing translational clinical trials may lead to rapid improvements in the management of patients.”
Ado-trastuzumab emtansine was added as a preferred therapeutic option for the treatment of HER2-positive metastatic breast cancer, including patients who have been previously treated with trastuzumab.
Consider use of everolimus (Afinitor) in addition to exemestane for women with hormone receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors, based on the results of the BOLERO-2 trial.