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Contemporary Treatment of Metastatic Non-Small Cell Lung Cancer

Contemporary Treatment of Metastatic Non-Small Cell Lung Cancer. Jeffrey A. Bubis , DO, FACOI, FACP Cancer Specialists of North Florida Baptist South and Fleming Island. Lung Cancer Stats. Leading cause of cancer death in U.S. Predicted 2014 demographics 224,210 new cases

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Contemporary Treatment of Metastatic Non-Small Cell Lung Cancer

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  1. Contemporary Treatment of Metastatic Non-Small Cell Lung Cancer Jeffrey A. Bubis, DO, FACOI, FACP Cancer Specialists of North Florida Baptist South and Fleming Island

  2. Lung Cancer Stats • Leading cause of cancer death in U.S. • Predicted 2014 demographics • 224,210 new cases • 116,000 men and 108,210 women • 159,260 deaths • 86,930 men and 72,330 women • 5 year OS is 16.6% http://seer.cancer.gov/statfacts/html/lungb.html)

  3. Classification • WHO • SCLC • NSCLC • NSCLC is 85% of all lung cancer cases • Squamous cell Carcinoma • Non-Squamous Cell Carcinoma • Adenocarcinoma (Most common) • Large cell Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J ThoracOncol 2011;6:244-285.

  4. Pathologic Evaluation • Biopsies should be with a core needle or with multiple FNA specimens • All specimens should be tested for: • EGFR • ALK • If limited tissue is available, this is more important than IHC • TTF-1 negative/p63 positive = SCC • TTF-1 positive/p63 negative = NSNSCLC

  5. Prognostic Factors • Early stage disease • Good performance status (ECOG 0, 1, 2) • Weight loss <5% • Female gender Finkelstein DM, Ettinger DS, Ruckdeschel JC. Long-term survivors in metastatic non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study. J ClinOncol 1986;4:702-709.

  6. Treatment Options • Stage I-II • Surgery +/- chemotherapy • Radiotherapy (non surgical candidates) • Stage III • Surgery + chemotherapy • Chemotherapy+radiation • Chemotherapy • Stage IV • Systemic therapy +/- radiation NCCN guidelines http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site.

  7. Treatment Options For Metastatic Disease • Cytotoxic chemotherapy • Pros • Reduces symptoms • Improves quality of life • Improves overall survival • Cons • Nonspecific

  8. Treatment Options For Metastatic Disease • Targeted Therapy • Pros • Reduces symptoms • Improves quality of life • Improves progression free survival • May have reduced toxicity relative to cytotoxic therapy • Cons • Nonspecific

  9. Historic Perspective on Front Line Therapy of NSNSCLC • Until the mid-2000’s • Platinum and non-platinum doublet therapies • Carboplatin + taxane • Carboplatin + gemcitabine • 2006 • Bevacizumab FDA approved • 2009 • Pemetrexed FDA approved

  10. EGFR Activating Mutations • Seen in 15% of NSCLC in the U.S. • More frequent in non-smokers • Up to 62% of Asian (especially females) • Favorable prognosis • Predicts sensitivity to EGFR tyrosine kinase inhibitors • Erlotinib and afatinib

  11. EGFR Positive • EGFR TKIs • Front line • Improve PFS compared to standard platinum-based therapy • Continue until progression or intolerance • Second line

  12. EGFR TKI Data • Meta-analysis of 13 phase III trials with 2620 patients demonstrated • PFS improved • No change in OS Lee CK, Brown C, Gralla RJ, et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst 2013; 105:595.

  13. EGFR TKI Data • OPTIMAL • 154 patients • Erlotinibvs Carboplatin/Gemcitabine • PFS 13.1 vs 4.6 months • ORR 83 vs 36% Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12:735.

  14. EGFR TKI Data • EURTAC • 174 patients • Erlotinib vs. platinum doublet • PFS 9.7 vs 5.2 months • OS 19.3 vs 19.5 months • Crossover design Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012; 13:239.

  15. EGFR TKI Toxicities • Rash • Usually mild • Usually responsive to topical therapies or doxycycline • Diarrhea • Rarely severe • Usually responsive to loperamide • Interstitial pneumonitis • Hepatic toxicity

  16. ALK Translocation • Present in 4% of NSCLC in the U.S. • More frequent in nonsmokers • More frequent in younger patients • Predicts for sensitivity to ALK tyrosine kinase inhibitors • Crizotinib

  17. ALK Trial Data • 347 patients with ALK+ NSCLC that was previously treated with a platinum doublet randomly assigned to crizotinib or single agent chemotherapy. Crossover was allowed. • PFS was better with crizotinib (7.7 vs 3.0 months) • RR was better with crizotinib (65 vs 20%) • OS unchanged (20.3 vs. 22.8 months) Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368:2385.

  18. ALK TKI Toxicities • Visual disturbances (dark to light transitions) • N/V/D/constipation • Transaminitis • Bradycardia • QTc prolongation • Serum testosterone depression • Pneumonitis

  19. Other Targets Under Investigation

  20. Immunotherapy • Anti-CTLA-4 • Anti-PD1/PDL1 • Vaccines

  21. Thank you.

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