NCCN Updates Its Clinical Practice Guidelines

Audrey Andrews

May 2013, Vol 4, No 4 - NCCN Annual Conference

Hollywood, FL—Updates to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines® were presented at the 2013 NCCN annual conference. The updates were minor for most tumor sites, but new guidelines were introduced for penile cancer and for survivorship.

New Guidelines for Penile Cancer
The NCCN issued inaugural guidelines for penile cancer, a rare malignancy. The standard of care remains complete tumor excision and eradication of negative margins, but in many patients, less invasive management can be appropriate. For superficial disease, less invasive options can be considered, based on the stage and grade of the tumor. These options include topical treatment with imiquimod 5% (Aldara) or with 5-fluorouracil cream (Efudex), which can produce “excellent outcomes,” according to Philippe E. Spiess, MD, MSc, Genitourinary Oncologist, H. Lee Moffitt Cancer Center, Tampa, FL.

For more extensive tumors, radical surgery is the chief recommendation. Options include wide local excision, laser treatment, radiation therapy, glansectomy, and partial/total penectomy. Penile-preserving surgery maintains function and quality of life in patients with small lesions, where negative margins can be obtained. For bulky disease with positive lymph nodes, neoadjuvant chemotherapy has been proved effective. A nomogram is recommended for predicting metastatic lymph node involvement, because it outperforms the conventional clinical risk categories. The NCCN does not recommend dynamic sentinel-node biopsy, because of its low sensitivity and inadequacy in detecting occult inguinal disease.

New Survivorship Guidelines
A growing appreciation of the unmet needs of cancer survivors has led to a new set of guidelines for survivorship. Topics include anxiety and depression, cognitive function, exercise, immunizations and infections, fatigue, pain, sexual function, and sleep disorders.
“The survivorship guidelines are intended as a library of tools for a provider to use when assessing a cancer survivor,” said Crystal S. Denlinger, MD, Co-Site Director, Internal Medicine Residency Program, Fox Chase Cancer Center, Philadelphia, PA.

The NCCN recommends physical activity and returning to daily activities, tailored to the individual’s abilities and preferences, as soon as possible after cancer treatment. The general recommendation is at least 150 minutes of moderate-intensity activity weekly, coupled with strength training and stretching. The document includes an assessment pathway and advice for specific populations (eg, for patients with lymphedema); offers examples of light, moderate, and vigorous exercise; and suggests strategies to motivate patients.

Cognitive dysfunction can occur as a complication of cancer treatment. The guidelines discuss general principles of cognitive dysfunction and provide an evaluation pathway, specific assessments, and practical interventional strategies, but this is still an area that is not well understood and is not backed by strong data.

The guidelines encourage immunizations based on age and medical condition as part of standard practice. Vaccinations against influenza, pneumonia, meningitis, and hepatitis are considered safe for patients with cancer, but live attenuated vaccines are contraindicated or should be used with caution. Principles for zoster vaccination in cancer or transplant survivors are included.

Sexual dysfunction is common for cancer survivors, and clinicians should assess level of sexual activity (past and present), the impact of cancer therapy, sexual concerns, comorbidities, risk factors, and psychosocial factors. The guidelines include validated tools for assessment: a brief sexual symptom checklist for women and a sexual health inventory for men.

Acute Promyelocytic Leukemia: A Nonchemotherapy Option
“For the first time, the NCCN guidelines have taken chemotherapy out of the upfront treatment for acute promyelocytic leukemia [APL],” said Margaret R. O’Donnell, MD, Associate Clinical Director, Department of Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA.

The guidelines for APL were changed as a result of a recent study (Lo-Coco F, et al. Blood. 2012;120:Abstract 6). For patients with low- or intermediate-risk APL, the guidelines now recommend induction with all-transretinoic acid plus arsenic trioxide.

New Agents in Colorectal Cancer
Two new agents are now included in the NCCN guidelines for metastatic colorectal cancer—ziv-aflibercept (Zaltrap) and regorafenib (Stivarga)—although their overall benefit is relatively minor, acknowledged Leonard Saltz, MD, Chief of the Gastrointestinal Oncology Service, and Head of the Colorectal Oncology Section, Memorial Sloan-Kettering Cancer Center, New York. “We had hoped ziv-aflibercept would be the next step forward, but in the registration study, it provided only a 1.5-month overall survival benefit,” Dr Saltz noted.
In the updated guidelines, ziv-aflibercept is acceptable when added to the FOLFIRI regimen or to irinotecan, but it should not be used as a single agent, in combination with FOLFIRI after failure of FOLFIRI plus bevacizumab (Avastin), or added to a failed regimen. Bevacizumab was also added as an option after first disease progression, in combination with the FOLFIRI regimen, with irinotecan, with the FOLFOX regimen, or with capecitabine (Xeloda) plus oxaliplatin (Eloxatin).
Regorafenib was added to the guide­lines as a treatment option after first, second, or third disease progression, depending on previous lines of therapy used, based on the 1.4-month survival advantage seen in the CORRECT trial (Grothey A, et al. Lancet. 2013;381:303-312).

Giant-Cell Tumor of Bone
New treatment pathways for giant-cell tumor of bone (GCTB) and chordoma debuted in the updated version of the guidelines for bone cancer. These are rare neoplasms and most clinicians are unfamiliar with them. Although GCTB is considered a benign disease, it carries a 2% risk for metastasis.

Intralesional excision with the use of a high-speed burr is advised rather than more extensive surgery that requires skeletal reconstruction. Although recurrence is not uncommon, the use of adjuvant therapy—thermal or chemical—ameliorates this risk. In patients with unresectable or recurrent disease, denosumab (Prolia) can help restore the skeletal architecture and allow a joint-conserving procedure or avoidance of surgery altogether.

For localized disease, excision is recommended; if resection carries unacceptable morbidity, or if the tumor is unresectable, treatment options include serial embolization, denosumab, interferon, pegylated interferon, and/or radiotherapy. For metastatic disease, surgery is indicated if feasible. The recommended workup includes history, physical examination, cross-sectional imaging of the primary site, chest imaging, and biopsy, with optional bone scan.

New Agents in Multiple Myeloma
“We have wonderful new agents, at least a lot more potent than prior- generation drugs,” said Kenneth C. Anderson, MD, Director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, and Oncologist, Brigham and Women’s Hospital, Boston. The approval of the second-generation protea­some inhibitor carfilzomib (Kyprolis) led to its recent inclusion in the guidelines in combination with lenalidomide (Revlimid) plus dexamethasone for transplant candidates. This triplet joins a growing list of regimens that greatly increase response rates, Dr Anderson noted.

For relapsed and/or refractory disease, the updated guidelines also include carfilzomib as a preferred salvage therapy option, as well as the new immunomodulating drug pomalidomide (Pomalyst) plus low-dose dexamethasone. Other recommended regimens now include bortezomib (Velcade) plus vorinostat (Zolinza) and lenalidomide plus bendamustine (Treanda) and dexamethasone.

Updates in Non-Hodgkin Lymphoma
The growing use of lenalidomide by patients with non-Hodgkin lymphoma is reflected in the updated guidelines. New to the guidelines for the second-line treatment of stage I to II disease is lenalidomide, with or without rituximab (Rituxan). For chronic lymphocytic leukemia, first-line therapy now includes lenalidomide (continuous or intermittent dosing) as a treatment option, and bendamustine, with or without rituximab. For relapsed and/or refractory disease, lenalidomide, with or without rituximab, is a treatment option.

New TKIs in Thyroid Cancer
With the availability of 2 new tyrosine kinase inhibitors (TKIs), “these are exciting times in thyroid cancer,” said Robert I. Haddad, MD, Associate Professor of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston. TKIs now offer an option for patients with disease refractory to radioactive iodine.

In patients with advanced or meta­static medullary thyroid cancer, cabozantanib (Cometriq) and vandetanib (Caprelsa) have more than doubled progression-free survival. The guidelines now list both drugs as Category 1 treatments for unresectable disease that is symptomatic or asymptomatic and structurally progressive. Although not approved by the US Food and Drug Administration (FDA) for thyroid cancer, other small-molecule TKIs (eg, sorafenib, sunitinib) can be considered.

New Drugs Exploit Androgen Pathway in Prostate Cancer
Two new drugs approved by the FDA for the treatment of prostate cancer take advantage of the persistence of androgen receptor expression, even in patients with castration-resistant disease. Abiraterone acetate (Zytiga), an androgen synthesis inhibitor, and enzalutamide (Xtandi), an antiandrogen, have changed the treatment landscape, said Philip W. Kantoff, MD, Chief, Division of Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston.

The NCCN guidelines now include abiraterone plus prednisone as a Category 1 recommendation in the pre- and postchemotherapy settings, and enzalutamide as a Category 2A recommendation for docetaxel-naïve patients and a Category 1 recommendation after chemotherapy. “These drugs have a clinically meaningful impact on survival,” Dr Kantoff said.

Melanoma: Thin Lesions Can Forego SLNB
A substantial change to the melanoma guidelines pertains to the indication for sentinel lymph node biopsy (SLNB), which the panel concluded is not warranted for thin (ie, ≤0.75 mm) lesions. SLNB may be considered when conventional risk factors accompany these very thin lesions. Otherwise, patients with thin lesions should undergo wide excision, patients with lesions 0.76 mm to 1.0 mm should be considered for SLNB, and patients with lesions >1 mm require SLNB. The change has the potential to affect up to 75% of the patients with melanoma in the average practice.