GRACE Intro to Adv NSCLC 1st Line Chemo

An Introduction to Initial Chemotherapy for Advanced Non-Small Cell Lung Cancer (NSCLC) : 

An Introduction to Initial Chemotherapy for Advanced Non-Small Cell Lung Cancer (NSCLC) Howard (Jack) West, MD Medical Oncologist Medical Director, Thoracic Oncology Program Swedish Cancer Institute Seattle, WA President & CEO GRACE January, 2009

Sponsored by the Loving Family of Melissa Peterson : 

Sponsored by the Loving Family of Melissa Peterson Hoping to help the entire lung cancer community For information about sponsoring a presentation about a topic important to you, please e-mail info@cancergrace.org

Disclaimers : 

Disclaimers The information provided here includes views of the presenter that do not necessarily represent those of the Global Resource for Advancing Cancer Education (GRACE) in general, nor those of Swedish Cancer Institute. The contents of this program do not constitute medical advice and is intended to supplement but not replace input from an individual patient’s medical team.

Disclaimers : 

Disclaimers This program includes detailed medical information such as general cancer survival statistics and other information that may be discouraging or upsetting to certain people. It is important to remember that individual patients have very different outcomes, some far better and some worse than the numbers for the broader population.

Chemotherapy vs Best Supportive Care in Advanced NSCLC: The Meta-Analysis : 

Chemotherapy vs Best Supportive Care in Advanced NSCLC: The Meta-Analysis 11 trials (8 cisplatin-based) 1,190 patients (1,144 deaths) Trials w/cisplatin: 27% improvement in survival Median survival increase of 1.5 months (chemo vs no chemo) Absolute improvement in survival: 10% at 1 year Non-small Cell Lung Cancer Collaborative Group. BMJ. 1995;311:899-909.

Selected single agents with NSCLC activity : 

Selected single agents with NSCLC activity Older Agents Carboplatin Cisplatin Etoposide Ifosfamide Mitomycin C Vinblastine Vindesine Newer Agents Paclitaxel (Taxol) Docetaxel (Taxotere) Gemcitabine (Gemzar) Vinorelbine (Navelbine) Irinotecan (Camptosar) Topotecan (Hycamtin) Pemetrexed (Alimta)

Addition of New Agents to Cisplatin is Superior to Cisplatin Alone : 

Addition of New Agents to Cisplatin is Superior to Cisplatin Alone Wozniak, JCO 16: 2459-2465, 1998. Sandler, JCO 18: 122-130, 2000.

ECOG 1594: Randomized Trial of Platinum-Based Doublets for Advanced NSCLC : 

ECOG 1594: Randomized Trial of Platinum-Based Doublets for Advanced NSCLC Every 3 weeks AUC = 6 d1 225 mg/m2/3h d1 Carboplatin Paclitaxel Every 3 weeks 75 mg/m2 d1 75 mg/m2 d1 Cisplatin Docetaxel Every 4 weeks 100 mg/m2 d1 1 g/m2 d1,8,15 Cisplatin Gemcitabine Every 3 weeks 75 mg/m2 d2 135 mg/m2/24h Cisplatin Paclitaxel R A NDOMIZE Schiller, NEJM 346: 92-98, 2002 1207 pts, stage IIIB/IV (15/85%), PS 0-2 median age 63, M/F (64/36%)

Slide 9: 

Platinum vs. Non-Platinum Doublets in Advanced NSCLC: Schema and Efficacy Results R A N D Adv NSCLC N = 788 Carbo d1 Gemcitabine d1,8 every 21 days Taxol d1 Gemcitabine d1,8 every 21 days Carbo d1 Taxol d1 every 21 days Treat, Proceeding of ASCO 2005, A#7025

CALGB 9730: New Single-Agent vs. Platinum-Based Doublet : 

CALGB 9730: New Single-Agent vs. Platinum-Based Doublet Stage IIIB/IV NSCLC N = 561 R A N D O M I Z E Carboplatin AUC = 6 Paclitaxel 225 mg/m2 q21d Lilenbaum, J Clin Oncol, 2005 Paclitaxel 225 mg/m2 q21d

CALGB 9730: Efficacy of Carbo/Taxol vs. Taxol Alone : 

CALGB 9730: Efficacy of Carbo/Taxol vs. Taxol Alone Lilenbaum, J Clin Oncol, 2005 Overall Survival

How Long to Treat? Four Cycles is Enough : 

How Long to Treat? Four Cycles is Enough St. IIIB/IV NSCLC PS 0-1 (N=230) R A N D O M I Z E Carboplatin AUC 6 Paclitaxel 200 mg/m2 every 3 wks x 4 cycles Carboplatin AUC 6 Paclitaxel 200 mg/m2 every 3 wks Treating to progression Socinski, JCO 20: 1335-1343, 2002

Results: Four is as Good as More : 

Results: Four is as Good as More All efficacy endpoints equal Only difference is more neurotoxicity with additional Rx Socinski, JCO 20: 1335-1343, 2002

Three Drugs NOT Better than Two : 

Three Drugs NOT Better than Two Many recent trials show response rate better, but NO improvement in survival Significantly greater side effects; major risks of being hospitalized for infections or other problems NOT standard, not routinely used (Delbaldo, JAMA 2004)

Summary: First Line Chemo for Advanced NSCLC in Healthier (Good Performance Status) Patients : 

Summary: First Line Chemo for Advanced NSCLC in Healthier (Good Performance Status) Patients Multiple platinum-based doublet chemo combinations (cisplatin or carboplatin) are overall remarkably comparable in activity Differences are largely in anticipated side effects and treatment schedules Non-platinum doublets are also a more or less comparable but not superior option We typically pursue an upper limit of 4-6 cycles of first line chemo Doublets are superior to single drug regimens overall for more fit patients, but three drug combinations are not superior to two Upcoming topic: some chemo doublets + targeted therapy have shown a survival benefit vs. doublet chemo alone

Questions and Comments? : 

Questions and Comments? Posts on several of these topics available in more detail at www.CancerGrace.org/lung/ Comments and questions can be left at www.tinyurl.com/FirstLinechemoAdvNSCLC (people must be a GRACE member to leave comments/questions)