Non-small Cell Lung Cancer in Practice An Expert Commentary With Karen Reckamp, MD A Clinical Context Report
Clinical Context: NSCLC in Practice Expert Commentary Jointly Sponsored by: and
Clinical Context: NSCLC in Practice Expert Commentary Supported in part by educational grants from Boehringer Ingelheim Pharmaceuticals.
NSCLC in Practice Clinical Context Series The goal of this program is to provide upto-date information and multiple perspectives on the pathogenesis, patient identification, symptoms, risk factors, and current and emerging treatments and best practices in the management of NSCLC.
NSCLC in Practice Clinical Context Series Target Audience Thoracic surgeons, medical oncologists, radiation oncologists, radiologists, pulmonologists, pathologists, respiratory therapists, primary care physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals involved in the management of NSCLC.
Activity Learning Objective Upon successful completion of this educational program, participants should be able to: Review the relevance and significance of the activity in the broader context of clinical care
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Discussant Karen L. Reckamp, MD Associate Professor, Medical Oncology and Therapeutics Research Co-chair, Lung Cancer and Thoracic Oncology Program Medical Oncology & Therapeutics Research City of Hope Duarte, Calif
Disclosure Information Karen Reckamp, MD, disclosed the following relevant financial relationships: Received Research Support: Amgen, Astellas, GlaxoSmithKline, Pfizer Consulting/Advisory Board: Amgen This activity may review off-label or investigational information without any recommendation on their use.
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Non-Small Cell Lung Cancer 5-year Survival by Stage at Diagnosis Stage I 60% to 80% Stage II 40% to 50% Stage IIIA 23%* Stage IV (metastatic) <10% All stages combined ~15% *Varies by cancer characteristics Source: National Cancer Institute
National Lung Screening Trial CT X-ray N 26,722 26,732 Smokers Current Former 12,862 13,860 12,900 13,832 Positive Screens 24.2% 6.9% False Positives 96.4% 94.5% Cancers Detected 1,060 941 Cancer Incidence (per 100,000 person/ years) 645 572 Lung Ca Mortality* (per 100,000 person/years) 247 309 All-cause Mortality (N)** 1,877 2,000 *P=0.004 **P=0.02 Source: N Engl J Med 2011; 365: 395-409
Non-Small Cell Lung Cancer Defined by Stage Stage I Localized, no nodal involvement 1A - <3 cm 1B - 3 cm Stage II Localized, +/- nodal involvement IIA - <3 cm, node+ IIB - 3 cm, node+ Stage IIIA Large, spread to nearby nodes; any size, spread to more distant nodes Stage IIIB Any size, spread to distant nodes, involvement of other tissue/organs in chest, or with pleural effusion Stage IV Metastatic Source: National Cancer Institute
Mutation Testing in NSCLC Test EGFR ALK KRAS RET ROS1 Indication All adenocarcinoma All adenocarcinoma Adenocarcinoma, selective EGFR-,ALK-negative, light smokers EGFR-, ALK-negative, light smokers
Drug Therapy for NSCLC* Agent Docetaxel Pemetrexed Bevacizumab Erlotinib Gefitinib Sunitinib Vandetinib Crizotinib Ponatinib Target Chemotherapy, nonspecific Chemotherapy, nonspecific Vascular endothelial growth factor (VEGF), angiogenesis Epidermal growth factor receptor (EGFR) EGFR VEGF VEGF and RET ALK and ROS1 RET *Examples, not a comprehensive guide
Methods Personalized Medicine for NSCLC The BATTLE Trial Serial core needle biopsies to measure activity of 11 biomarkers in four molecular pathways and six proteins Adaptive randomization to therapy on basis of biomarker findings or equal randomization without regard to biomarker status Treatment options: vandetanib, erlotinib, erlotinib + bexarotene, sorafenib Ongoing treatment guided by biomarker results in adaptive randomization arm
Personalized Medicine for NSCLC (cont d) The BATTLE Trial Results N=255 (adaptive 158), (equal 97) Disease control at 8 weeks: 42% (adaptive) versus 37% (equal) Median survival: 11.3 months (w/disease control) versus 7.5 months (without), P=0.002 Source: Cancer Discovery 2011; 1: 44-53.
Palliative Care and End-of-life Decisions For patients with advanced-stage disease, be realistic about the poor prognosis from the beginning. Emphasize that advanced-stage NSCLC can be treated, even though cure is unlikely. Advances in chemotherapy and palliative care have extended good-quality life for most patients. Early palliative care not only makes patients more comfortable but can extend life. Encourage participation in clinical trials. Maintain a healthy balance between optimism and realism.
SUMMARY Early diagnosis has the greatest impact on survival in NSCLC. The 5-year survival for NSCLC is directly related to stage at diagnosis, ranging from 80% at stage 1 to <10% at stage IV. The National Lung Screening Trial showed that lowdose radiation CT can reduce lung cancer mortality compared with standard x-ray in high-risk patients. Widespread adoption of low-dose CT for lung cancer screening has been complicated by unresolved questions related to cost, a high rate of false-positive results, and uncertainty about the target population for screening.
SUMMARY (cont d) Once largely ignored as a component of lung cancer treatment, chemotherapy has evolved into an essential part of treatment for many patients. The evolution of targeted therapies has led to incremental improvement in survival for NSCLC, beyond that achieved with conventional chemotherapy. Identification of generic mutations in tumors has increased the potential for individualized or personalized treatment of NSCLC. Tumors with specific types of mutations have demonstrated increased sensitivity to drugs that target those mutations.
SUMMARY (cont d) Incremental improvement in survival achieved with chemotherapy and targeted drugs has led to substantial improvement in survival for patients with NSCLC. End-of-life discussions should be initiated early in patients with advanced-stage NSCLC and become a part of ongoing decision making about patient care. Early implementation of palliative care not only can improve patients comfort and quality of life but extend survival in some cases. Clinicians should help patients and families maintain an appropriate balance between hope for patients with NSCLC and the realities of the disease.