In 1996, the National Comprehensive Cancer Network® (NCCN®) published its first set of Clinical Practice Guidelines in Oncology (NCCN Guidelines®) covering 8 tumor types. Guidelines are now published for more than 60 tumor types and topics. Some of the key updates were presented at NCCN’s 23rd Annual Conference and are briefly summarized here.
“There is a great deal interest now in giving all total neoadjuvant therapy, ie, chemotherapy, then chemoradiation, then surgery or chemoradiation, then chemotherapy, then surgery. Either is now recommended in the guidelines.”
—Christopher Willett, MD
Christopher Willett, MD
A number of important changes were made to the NCCN Guidelines for Rectal Cancer, as presented by Christopher Willett, MD, of Duke University Medical Center, Durham, North Carolina:
“With data from the IDEA trial, we now have a platform for a framework to discuss these data with patients, and that’s the strength of IDEA.”
—Axel Grothey, MD
Axel Grothey, MD
Axel Grothey, MD, of the Mayo Clinic Cancer Center, Phoenix, and Alan Venook, MD, of the University of California, San Francisco, described revisions to the NCCN Guidelines for Colon Cancer:
“If you reflect what’s gone on over the past couple of years, it’s really been the era of the CDK4/6 inhibitors…. Reflected in the guidelines are a number of different options among the three CDK4/6 inhibitors, with a category 1 level of evidence.”
—William J. Gradishar, MD
William J. Gradishar, MD
Several speakers updated attendees on breast cancer management, including William J. Gradishar, MD, of Northwestern University, Chicago; Sharon H. Giordano, MD, MPH, of The University of Texas MD Anderson Cancer Center, Houston; and Anthony D. Elias, MD, of the University of Colorado Cancer Center, Denver.
These updates for patients with HER2-positive or hormone receptor–positive disease were presented:
Screening and Diagnosis of Hepatocellular Carcinoma
“When we screen for hepatocellular carcinoma, we are finding disease at a stage that is amenable to potentially curative treatment and, associated with that, improvements in survival at 1, 3, and 5 years.”
—Anne M. Covey, MD
Anne M. Covey, MD
Anne M. Covey, MD, of Memorial Sloan Kettering Cancer Center, New York, described the updates to the guidelines for screening and diagnosis of hepatocellular carcinoma:
“There is a growing list of approved targets and therapies included in the 2018 NCCN Guidelines [for Non–Small Cell Lung Cancer] as well as emerging targets. Why does this matter? Because targeted therapies improve survival.”
—Karen L. Reckamp, MD, MS
Karen L. Reckamp, MD, MS
The 2018 NCCN Guidelines Updates for Targeted Therapy for Patients With Metastatic Non–Small Cell Lung Cancer (NSCLC) recommend molecular testing for first initial diagnosis, since targeted therapies that can improve outcomes for many patients are available, explained Karen L. Reckamp, MD, MS, of City of Hope Comprehensive Cancer Center, Duarte, California.
Approved therapies are available for patients with epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, ROS1 rearrangements, and BRAF mutations. The list of emerging “actionable” targets is growing. The 2018 NCCN Guidelines incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib (Tagrisso) and the ALK inhibitor alectinib (Alecensa), as first-line preferences.
“It is a very exciting time in renal cell carcinoma, with new treatments. Most new treatments are for clear cell carcinoma.”
—Eric Jonasch, MD
Eric Jonasch, MD
There were several updates to the 2018 NCCN Guidelines for Kidney Cancer, noted Eric Jonasch, MD, of the Von Hippel-Landau Clinical Center at MD Anderson Cancer Center in Houston. Adjuvant sunitinib (Sutent) is the first adjuvant therapy to be endorsed by the 2018 NCCN Guidelines for patients with stage II and III high-risk renal cell carcinoma and clear cell histology (category 2 B).
Two new options are included for the first-line treatment of advanced renal cell carcinoma:
“If you do it properly [ie, intermittent androgen-deprivation therapy, (ADT)], there is a significant quality-of-life benefit. We can be more intelligent and personalize ADT.”
—James L. Mohler, MD, and Peter R. Carroll, MD
Peter R. Carroll, MD
James L. Mohler, MD
The 2018 NCCN Prostate Cancer Guidelines recommend baseline screening beginning at age 45, which is younger than in the other sets of guidelines, explained Peter R. Carroll, MD, of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.
Risk stratification and proper staging workup are emphasized more strongly in the 2018 iteration of the NCCN Guidelines than in the past, explained James L. Mohler, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York.
The 2018 NCCN guidelines provide alternatives to routine biopsy in men with elevated prostate-specific antigen (PSA) levels, including the use of serum and urine biomarkers and multiparametric MRI before moving to biopsy.
Active surveillance is advised for very low–risk and low-risk patients.
Molecular testing and germline testing are recommended early in the course of disease for patients with a strong family history (defined for the first time in the new guidelines), with the aim of developing more personalized medicine.
Germline testing is advised for more advanced disease. Testing for germline and/or somatic mutations should be considered in all men with high-risk, very high–risk, regional, or metastatic prostate cancer.
Men with BRCA1, BRCA2, ATM, PALB2, and FANCA should be referred for genetic counseling and early use of platinum chemotherapy or enrollment in a clinical trial. Men with MSI and deficient MMR should be referred for genetic counseling and are eligible for pembrolizumab when they fail to respond to ADT.
According to the 2018 NCCN Guidelines, patients with asymptomatic castration-naive metastatic prostate cancer should receive intermittent ADT; they should be made aware of a possible small trade-off in overall survival for improved quality of life during the off cycle. For symptomatic men, continuous ADT should be considered, but if the PSA level decreases to < 4 ng/mL and certainly < 0.2 ng/mL, intermittent ADT is reasonable.
Younger healthier men should consider docetaxel or abiraterone (Zytiga) added to ADT, whereas older and/or unhealthier men should receive ADT.
Apalutamide (Erleada) is now one of the recommended second-generation antiandrogens incorporated in the 2018 NCCN Guidelines.
The updated guidelines distinguish between management of patients with visceral metastasis versus skeletal metastasis.
Gliomas: Molecular Pathology in Staging and Treatment of Anaplastic Gliomas
“These three markers [co-deletion of 1p and 19q, IDH 1 and IDH 2 mutations, and MGMT promoter methylation] are currently the most important clinical markers in managing malignant gliomas.”
—Matthias Holdhoff, MD, PhD
The 2018 NCCN Guidelines incorporate molecular characteristics and pathologic characteristics in the staging and treatment of anaplastic gliomas.
Testing for IDH1 and IDH2 mutations and co-deletion of 1p and 19q is now a key element in the diagnostic workup of gliomas based on the recently published World Health Organization classification on brain tumors of 2016.
Matthias Holdhoff, MD, PhD
The highest level of evidence for the treatment of newly diagnosed anaplastic oligodendrogliomas with co-deletion of 1p and 19q has the regimen of radiation and chemotherapy with PCV (procarbazine, lomustine, vincristine). An ongoing prospective trial in these cancers, the so-called CODEL trial, is formally comparing this regimen with the somewhat better tolerated regimen of radiation and temozolomide (which is the current standard regimen for glioblastomas), explained Matthias Holdhoff, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore.
Acute Myeloid Leukemia: Emphasis on Genetics
“It is becoming increasingly important to become aware not only of a particular mutation but of the spectrum of mutations that occurs in a given patient [with acute myeloid leukemia]. They have important interactions that lead to dramatic differences in overall survival.”
—Martin S. Tallman, MD
Martin S. Tallman, MD
The diagnosis, staging, and treatment of acute myeloid leukemia (AML) have evolved based on the identification of important genetic alterations and drugs to target those genes. Cytogenetic abnormalities are the main concern in managing AML, explained Martin S. Tallman, MD, of Memorial Sloan Kettering Cancer Center, New York. Among important genetic aberrations are CEBP-alpha, FLT3, IDH1, IDH2, P53, and NPM1. The company these genetic abnormalities keep—ie, their combinations—affects prognosis.
Four drug approvals of novel agents have improved outcomes in patients with AML: midostaurin (Rydapt; targeted to FLT3), gemtuzumab (for CD33-positive AML), CPX-351 (a 5:1 formulation of daunorubicin/cytarabine for treatment-naive patients), and isocitrate dehydrogenase (IDH) inhibitors enasidenib and ivosidenib (for relapsed or refractory patients with IDH mutations). Achieving minimal residual disease is recognized as an increasingly important milestone. ■
DISCLOSURE: For full disclosures of all speakers, visit https://www.nccn.org/disclosures/guidelinepanellisting.aspx.