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NCCN Clinical Practice Guidelines Update

May 2012, Vol 3, No 3

The 2012 updates to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology™ have elevated several drugs to category 1 recommendation and have changed the algorithm for work-up in some tumors. A synopsis of the key updates presented at the 2012 annual conference is reported here.

Breast Cancer

The breast cancer panel recommended a more conservative use of imaging modalities for assessing, staging, and conservative management of the axillae in selected patients.

“In the past, imaging studies in early-stage disease were listed as ‘consider the following,’ but updated guidelines have shifted toward recommendations of when clinicians should not perform certain ones,” said Benjamin O. Anderson, MD, of the University of Washington/Seattle Cancer Care Alliance. “We are moving away from the concept in early-stage disease that the patient should routinely get a battery of tests, which often will mislead us.”

Routine systemic tumor staging is not indicated for early breast cancer in the absence of signs or symptoms of possible metastatic disease. Specifically, the guidelines now recommend the following strategies:

  • Bone scans if localized bone pain or elevated alkaline phosphatase are present
  • Abdominal ± pelvic diagnostic computed tomography (CT) or magnetic resonance imaging (MRI), but not ultrasound, in the presence of elevated alkaline phosphatase, abnormal liver function tests, abdominal symptoms, or abnormal physical examination of the abdomen or pelvis
  • Chest diagnostic CT if pulmonary symptoms are present.

For clinical stage IIIA breast cancer (T3N1), the clinician can consider chest diagnostic CT, abdominal ± pelvic CT or MRI, bone scan or fluoride positron-emission tomography (PET)/CT, and 18fluorodeoxyglucose (FDG)-PET/CT, which is considered equivalent to bone scanning. “What is new is the use of fluoride PET/CT looking for bone lesions; FDG-PET/CT is still optional,” Dr Anderson said.

Based on the landmark American College of Surgeons Oncology Group Z0011 study (Guiliano AE, et al. JAMA. 2011;305:569-575), which showed no difference in locoregional recurrence or survival whether patients underwent complete axillary lymph node dissection (ALND) or sentinel lymph node biopsy only, the recommendations for managing the axillae have changed. The panel stated that ALND can be avoided in patients meeting the strict Z0011 criteria: T1-T2 clinically node-negative disease and 1 or 2 involved sentinel lymph nodes, and treated with breast-conserving surgery and whole-breast radiation.

Patients with metastatic disease should be assessed for estrogen/progesterone receptor and HER2 status, if these are unknown or are originally negative or not overexpressed based on high rates of discordance observed in multiple studies.

The guidelines also contain new recommendations for monitoring metastatic disease and discourage the use of PET scanning in this setting.

Although not a recommendation, the panel stated that postmenopausal endocrine-sensitive patients with advanced HER2-negative disease may benefit from the combination of anastrozole (Arimidex) plus fulvestrant (Faslodex) therapy, and from the addition of everolimus (Afinitor) to exemestane (Aromasin).

Non-Hodgkin Lymphoma Within the Non-Hodgkin Lymphoma Guidelines™, the NCCN panel introduced inaugural recommendations for the rare but aggressive disorder of mature T-cells known as T-cell prolymphocytic leukemia (T-PLL). “Most patients with T-cell prolymphocytic leukemia are symptomatic, with fairly aggressive disease and need treatment,” said Leo I. Gordon, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

The treatment approach is based on the presence or absence of symptoms. Asymptomatic patients can be observed until disease progression, or until occurrence of symptoms. Previously untreated patients with symptomatic disease should receive intravenous (IV) alemtuzumab (Campath), based on a 2011 study in which IV alemtuzumab produced an overall response rate of 91%, an 81% complete response rate, and median survival of 15 to 19 months.

In addition to the T-PLL recommendations, the panel also advised testing for MYC positivity for all diffuse large B-cell and related lymphomas because of the poor prognostic impact related to this feature. For hairy-cell leukemia, the 2012 NCCN algorithm for immunophenotyping/genetic testing in the differential diagnosis of mature B-cell and natural killer T-cell neoplasms was also revised.

Malignant Melanoma

Immunotherapy with the monoclonal antibody ipilimumab (Yervoy) and targeted therapy with the BRAF inhibitor vemurafenib (Zelboraf) were added to the guidelines as category 1 options for the first-line treatment of systemic melanoma. Although dacarbazine (DTIC), temozolomide (Temcad), and taxane combinations remain options, “enthusiasm for these other agents has rapidly declined,” said John A. Thompson, MD, of the Seattle Cancer Care Alliance.

Ipilimumab led to overall survival (OS) improvements in previously treated patients in the MDX-010-20 trial and in previously untreated patients in the CA184-024 trial.

In patients with the BRAF V600 Emutation, vemurafenib improved OS as well (Chapman PB, et al. N Engl J Med. 2011;364:2507-2516). In a more recent study (Sosman JA, et al. N Engl J Med. 2012;366:707-714), vemurafenib induced clinical responses in more than 50% of patients with the mutation. The results with vemurafenib have been “striking,” Dr Thompson noted, observing that 80% of patients experience tumor shrinkage, and median survival has reached 16 months, “much better than expected in pretreated metastatic melanoma.”

The panel emphasized the need to screen patients with metastatic disease for BRAF status, which, along with degree of disease, can dictate choice of first-line treatment.

In addition, the panel does not recommend routine imaging and blood work for clinical stage IIA melanoma lacking specific signs and symptoms, but does recommend that for early-stage disease, sentinel lymph node biopsy be discussed and offered to patients.

Non–Small-Cell Lung Cancer

The pathologist should be an integral part of the non–small-cell lung cancer (NSCLC) management team, not just for diagnosis but for treatment planning as well, said Richard T. Cheney, MD, of Roswell Park Cancer Institute, Buffalo, NY. The panel updated the section on principles of pathologic review to reflect the growing role of the pathologist in this malignancy.

“We need close collaboration among all providers, and the pathologist has a role at all levels,” Dr Cheney pointed out. “The more involved the pathologist, the greater the likelihood that you will come up with the right answers.”

The guidelines refined the use of chemotherapy in the adjuvant setting and molecularly targeted agents for metastatic NSCLC, and added crizotinib as an option for advanced disease in patients with the EML4-ALK alteration.

“We see dramatic responses, and some are durable, with crizotinib,” observed Ramaswamy Govindan, MD, of Siteman Cancer Center and Washington University School of Medicine, St. Louis, MO. The NSCLC panel also emphasized the need for sufficient tissue for molecular analysis and revised the classifications for adenocarcinomas.

Renal-Cell Carcinoma

The recent US Food and Drug Administration approval of the multi–tyrosine kinase inhibitor axitinib (Inlyta) led to its inclusion as a category 1–recommended second-line option for metastatic renal-cell carcinoma (RCC) and a category 3 option in nonclear-cell RCC. The drug joins a long list of targeted agents for this disease, noted Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, Harvard Medical School.

“Based on the importance of the vascular endothelial growth factor and mTOR pathways in RCC, drugs hitting these targets have not only proved effective in this malignancy, but the results have been replicated in large phase 3 trials,” Dr Choueiri noted. “I have yet to see, in other solid tumors, the approval of 7 drugs in just 6 or so years.”

Hodgkin Lymphoma

As initial treatment for favorable stage IA or IIA Hodgkin lymphoma, the panel gave category 1 recommendations to both the ABVD regimen (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) and Stanford V regimen (doxorubicin, vinblastine, mechlorethamine, etoposide, bleomycin, vincristine, and prednisone) to be administered along with involved field radiotherapy.

“Stanford V is an acceptable regimen, particularly for patients who may have some underlying cardiac disease,” said Leo I. Gordon, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

The guidelines do not recommend routine PET surveillance after treatment of early disease, unless relapse is suspected, or bone marrow biopsy for favorable disease.

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