ASCO is updating its recommendations for managing care in patients with early- and late-stage lung cancer. One set of recommendations will include a large guideline update on the use of systemic treatment for patients with stage IV non-small cell lung cancer (NSCLC). A second set of recommendations, which was recently published, covers the rapidly advancing area of molecular testing for patients with either early-stage or advanced lung cancer. Forty percent of patients have stage IV NSCLC at the time of diagnosis. 1
There is also an endorsement that focuses on individuals with locally advanced NSCLC, who make up a growing proportion of diagnosed cases. 2 The guideline endorsement will provide important guidance on the use of curative-intent external-beam radiotherapy in individuals with this disease.
Endorsement of Lung Cancer Biomarker Guideline
In October 2014, ASCO endorsed a guideline from the College of American Pathologists (CAP), the International Society for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) on molecular testing of patients with lung cancer. The guideline focuses on EGFR and ALK testing, and when and how to do the testing.
‘It is already more or less standard to test biomarkers and use them to guide treatment decisions, but the hope is that the guideline will help close the gap for the minority of patients who are not tested and help clarify among oncologists for which patients [testing] is recommended,’ said Natasha Rekhtman, MD, PhD, of Memorial Sloan Kettering Cancer Center, and co-chair of the ASCO endorsement, along with Natasha B. Leighl, MD, of Princess Margaret Cancer Centre, Toronto.
The ASCO endorsement agrees with the recommendation that patients with lung adenocarcinoma, or mixed lung cancer with a component of adenocarcinoma, should be tested for EGFR and ALK mutations at the time of diagnosis or recurrence. However the caveat, according to both documents, is that squamous or small cell lung cancer should be tested for EGFR and ALK in never-smokers because the tumors may have an unusual pathology.
The documents also bring up the issue that, although testing in the early-stage setting allows more rapid initiation of therapy in patients who experience a relapse, it should be balanced against the extra cost for patients who do not have a recurrence. As lung cancer screening becomes more widespread and more patients are diagnosed with early-stage disease, the cost versus benefit balance of screening may need to be reevaluated, Dr. Rekhtman said. 3
The guideline does not recommend testing for other biomarkers. However, it states that testing for KRAS mutations may be performed initially to eliminate the need to probe for EGFR and ALK alterations, which are mutually exclusive with KRAS.
‘The field is moving toward multigene multiplex testing, so a lot of issues of what to test first will fall by the wayside,’ Dr. Rekhtman said.
As the endorsement notes, a number of new molecular alterations have recently been associated with lung cancer, including RET and ROS1 rearrangements. The CAP/IASLC/AMP guideline will be updated to include evaluations of new biomarkers, and as it is, ASCO will consider whether to endorse the updates.
Between 10%-15% of lung cancers harbor EGFR mutations, and another 3%-5% have ALK mutations. 4 Therapies targeting EGFR include erlotinib and afatinib, whereas ALK-targeted therapies are crizotinib and ceritinib.
Guideline on Chemotherapy for Stage IV NSCLC
ASCO is in the final stages of updating its guideline on systemic therapy for patients with stage IV NSCLC. It will make recommendations for patients depending on their cancer subtype and performance status for first-, second-, and third-line treatment and will include targeted therapy for patients with molecular alterations such as EGFR and ALK. The guideline is expected to be published in 2015.
‘The guideline can help oncologists organize the information and keep them on track on the things that they really already know but would like some additional reassurance that they are doing the right thing,’ said Gregory A. Masters, MD, of Helen F. Graham Cancer Center and co-chair of the guideline along with David H. Johnson, MD, of the University of Texas Southwestern Medical Center.
It could also give patients confidence that their oncologist is staying up-to-date with new therapies. ‘If you tell a patient that you’re treating them according to a national guideline, that is reassuring for him or her,’ Dr. Masters said.
The document is an update of a 2009 ASCO guideline on the topic and a 2011 focused guideline on maintenance therapy. Since the publication of those guidelines, more targeted therapies have become available, including ALK-targeting therapies, and there are more data on maintenance therapy. The guideline panel reviewed studies published between 2007 and 2014 and used a total of 73 phase III randomized controlled trials to develop the recommendations on more than 10 different therapeutic agents.
The guideline also stresses the role of palliative care and its integration with chemotherapy, targeted therapy, or supportive care.
Endorsement of Lung Cancer Radiotherapy Guideline
ASCO has endorsed a guideline from the American Society for Radiation Oncology on external-beam radiotherapy (EBRT) for patients with locally advanced NSCLC. Both the guideline and endorsement are expected to be published in 2015.
‘This treatment is with the intent of cure, and the question is, ‘How can we maximize the chance of cure for our patients in clinical practice?’ One way is by making sure that we have the latest knowledge and guidelines,’ said Andrea Bezjak, MD, of Princess Margaret Cancer Centre, Toronto, and co-chair of the endorsement along with Christopher G. Azzoli, MD, of Massachusetts General Hospital.
The endorsement is intended for patients with stage II or III locally advanced NSCLC who have unresectable disease, as well as those who are potential candidates for surgery. The endorsement also highlights the ambiguity of defining resectability.
Although the guideline focuses on EBRT, it also considers the context of the treatment, including EBRT with or without chemotherapy and neoadjuvant or adjuvant EBRT.
The endorsement will complement a 2007 joint guideline by ASCO and Cancer Care Ontario on adjuvant chemotherapy and radiation therapy for patients with resected NSCLC. 5
‘We need an update of both old and more recent evidence, and to focus on the large group of patients with locally advanced NSCLC that is not resectable,’ Dr. Bezjak said.