Presentation on theme: "Contemporary Treatment of Metastatic Non-Small Cell Lung Cancer"— Presentation transcript:
1Contemporary Treatment of Metastatic Non-Small Cell Lung Cancer Jeffrey A. Bubis, DO, FACOI, FACPCancer Specialists of North FloridaBaptist South and Fleming Island
2Lung Cancer Stats Leading cause of cancer death in U.S. Predicted 2014 demographics224,210 new cases116,000 men and 108,210 women159,260 deaths86,930 men and 72,330 women5 year OS is 16.6%
3Classification WHO SCLC NSCLC NSCLC is 85% of all lung cancer cases Squamous cell CarcinomaNon-Squamous Cell CarcinomaAdenocarcinoma (Most common)Large cellTravis 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:
4Pathologic Evaluation Biopsies should be with a core needle or with multiple FNA specimensAll specimens should be tested for:EGFRALKIf limited tissue is available, this is more important than IHCTTF-1 negative/p63 positive = SCCTTF-1 positive/p63 negative = NSNSCLC
5Prognostic Factors Early stage disease Good performance status (ECOG 0, 1, 2)Weight loss <5%Female genderFinkelstein 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:
6Treatment Options Stage I-II Stage III Stage IV Surgery +/- chemotherapyRadiotherapy (non surgical candidates)Stage IIISurgery + chemotherapyChemotherapy+radiationChemotherapyStage IVSystemic therapy +/- radiationNCCN guidelines
7Treatment Options For Metastatic Disease Cytotoxic chemotherapyProsReduces symptomsImproves quality of lifeImproves overall survivalConsNonspecific
8Treatment Options For Metastatic Disease Targeted TherapyProsReduces symptomsImproves quality of lifeImproves progression free survivalMay have reduced toxicity relative to cytotoxic therapyConsNonspecific
9Historic Perspective on Front Line Therapy of NSNSCLC Until the mid-2000’sPlatinum and non-platinum doublet therapiesCarboplatin + taxaneCarboplatin + gemcitabine2006Bevacizumab FDA approved2009Pemetrexed FDA approved
10EGFR Activating Mutations Seen in 15% of NSCLC in the U.S.More frequent in non-smokersUp to 62% of Asian (especially females)Favorable prognosisPredicts sensitivity to EGFR tyrosine kinase inhibitorsErlotinib and afatinib
11EGFR Positive EGFR TKIs Second line Front line Improve PFS compared to standard platinum-based therapyContinue until progression or intoleranceSecond line
12EGFR TKI DataMeta-analysis of 13 phase III trials with 2620 patients demonstratedPFS improvedNo change in OSLee 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.
13EGFR TKI Data OPTIMAL 154 patients Erlotinib vs Carboplatin/GemcitabinePFS 13.1 vs 4.6 monthsORR 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.
14EGFR TKI Data EURTAC 174 patients Erlotinib vs. platinum doublet PFS 9.7 vs 5.2 monthsOS 19.3 vs 19.5 monthsCrossover designRosell 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.
15EGFR TKI Toxicities Rash Diarrhea Interstitial pneumonitis Usually mildUsually responsive to topical therapies or doxycyclineDiarrheaRarely severeUsually responsive to loperamideInterstitial pneumonitisHepatic toxicity
16ALK Translocation Present in 4% of NSCLC in the U.S. More frequent in nonsmokersMore frequent in younger patientsPredicts for sensitivity to ALK tyrosine kinase inhibitorsCrizotinib
17ALK Trial Data347 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.