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

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Presentation on theme: "Contemporary Treatment of Metastatic Non-Small Cell Lung Cancer Jeffrey A. Bubis, DO, FACOI, FACP Cancer Specialists of North Florida Baptist South and."— Presentation transcript:

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%

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 Thorac Oncol 2011;6:

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 Clin Oncol 1986;4:

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

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 – Erlotinib vs 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 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 TranslocationMutationExpressionAmplificationAlteration ROS1RASMETFGFR1PIK3ca RETHER2AKT1 BRAFPTEN β-catenin DDR2 MEK1

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

21 Thank you.


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