1 / 34

FIRST-LINE THERAPY FOR ADVANCED NSCLC

FIRST-LINE THERAPY FOR ADVANCED NSCLC. Rogerio C. Lilenbaum, MD Clinical Associate Professor of Medicine University of Miami School of Medicine Director, Thoracic Oncology Program The Mount Sinai Comprehensive Cancer Center Miami Beach, FL. QUESTIONS FOR DISCUSSION.

taran
Download Presentation

FIRST-LINE THERAPY FOR ADVANCED NSCLC

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. FIRST-LINE THERAPY FOR ADVANCED NSCLC Rogerio C. Lilenbaum, MD Clinical Associate Professor of Medicine University of Miami School of Medicine Director, Thoracic Oncology Program The Mount Sinai Comprehensive Cancer Center Miami Beach, FL

  2. QUESTIONS FOR DISCUSSION • What are the options for 1st line therapy? • What is the optimal management of the elderly and the PS 2 patients? • What is the role of the non-platinum regimens? • What is the role of the molecular targeted agents in 1st line therapy?

  3. Cis/Vin and Cis/Gem vs. Cisplatin : Overall Survival 1.0 Cis/Gem vs Cisplatin Cis/Vin vs Cisplatin 100% 0.9 0.8 80% 0.7 0.6 60% Survival Probability 0.5 0.4 40% 0.3 0.2 20% P=.004 0.1 0.0 0% 25 0 5 10 15 20 0 12 24 36 48 60 N MS 1YS 2YS N MS 1YS 2YS Vin/Cis 206 8 36% 12% Cis 209 6 21% 7% Gem/Cis 260 9.0 39% 15% Cis 262 7.6 28% 8% J Clin Oncol 1998, 16:2459-64. J Clin Oncol 2000, 18:122-30.

  4. Cis-Vinorelbine vs Carbo-Paclitaxel SWOG 9509 Median Survival Survival N Deaths (Months) 1-Year 2-Year 1CBDCA+Pac 208 159 8 38% 15% CDDP+Vin 202 156 8 36% 16% 100% 80% 60% 40% 20% 0% 0 6 12 18 24 30 Months 1J Clin Oncol. 2001;19:3210-3218.

  5. A Phase III Four-Arm Trial in Advanced NSCLC RANDOMIZED Paclitaxel 135 mg/m2 over 24 hours, day 1Cisplatin 75 mg/m2, day 2 Gemcitabine 1000 mg/m2 days 1, 8, and 15Cisplatin 100 mg/m2 day 1 Docetaxel 75 mg/m2 day 1Cisplatin 75 md/m2 day 1 Paclitaxel 225 mg/m2 over 3 hours, day 1Carboplatin AUC=6 day 1 Stratification PS 0-2 WT Loss Stage - IIIB, IV Brain mets (+/-) Schiller, NEJM 2002:92-98

  6. A Phase III Four-Arm Trial in Advanced NSCLC *P = .002 by log rank test

  7. A Phase III Four-Arm Trial in Advanced NSCLC *P < 0.05 vs. Arm A

  8. Tax 326: Randomized Phase III Trialfor Advanced NSCLC Stratification Factors: Stage of Disease IIIB vs. IV RegionUS/Canada Latin America Europe/Lebanon Israel South Africa/AustraliaNew Zealand RANDOMIZE Docetaxel 75mg/m2 IVCisplatin 75mg/m2 IVQ 3 wks Docetaxel 75mg/m2 IVCarboplatin AUC 6IVQ 3 wks vs. Vinorelbine 25mg/m2 IV D 1, 8, 15 & 22Cisplatin 100mg/m2 IVD 1Q 4 wks Response assessment every 2 cycles

  9. Docetaxel/ Navelbine/ Docetaxel/ Cisplatin Cisplatin Carboplatin N Median survival (mo) 1-Yr survival (%) 2-Yr survival (%) Tax 326: Randomized Phase III Trialfor Advanced NSCLC 406 396 401 10.9 10.0 9.1 46 41 38 21 14 16 Cis/Tax vs. Cis/Nav Carbo/Tax vs Cis/Nav P=.044, Adjusted Log-Rank 2y Survival 21 vs 14%, p=.035 P=.66, Adjusted Log-Rank 2 y Survival 18 vs 14% Belani et al. 2001

  10. ASCO 2002Clinical Trials of 2-Drugs vs 1 1Proc ASCO 21:1a (A #2), 2002; 2Proc ASCO 21:291a (A #1162), 2002; 3Proc ASCO 21:291a (A #1163), 2002

  11. CALGB 9730 - DESIGN R A NDOMIZE Paclitaxel 225 mg/m2over 3 hours on day 1 IIIB/IV PS 0-1/2 Paclitaxel 225 mg/m2 + Carboplatin to AUC 6 Age / 70 Every 3 weeks for up to 6 cycles Lilenbaum, ASCO 2002

  12. CALGB 9730 – SURVIVAL Median follow-up was 19.7 months

  13. CALGB 9730 – OVERALL SURVIVAL Log-rank = 0.2022 Wilcoxon = 0.0125

  14. Gemcitabine/Carboplatin versus MIC Gemcitabine 1200 mg/m2d 1, 8 Carboplatin AUC = 5 d 1 q.21 days Stage IIIb/IV NSCLC PS 0-3 Mitomycin 6 mg/m2 Ifosfamide 3 g/m2 Cisplatin 50 mg/m2 Day1 q.21 days Rudd, ASCO 2002:A1164

  15. LLCG: GC vs MIP in Advanced NSCLCSurvival Med 1-Y GC 10.2m 38% MIP 6 .9m 28% GC Proportion Surviving Pts. MIP Months

  16. What are the options for 1st line therapy? PACLITAXEL DOCETAXEL VINORELBINE GEMCITABINE CISPLATIN CARBOPLATIN + • Patients with advanced NSCLC and good PS should be treated with a platinum-based doublet. • Platinum-based doublets are better than an old single agent (Cis) and a new single agent (Paclit) • All platinum-based doublets have comparable efficacy, but vary in cost and toxicity • Three-drug regimens are more toxic and no better than doublets • The preferred platinum analog remains controversial

  17. QUESTIONS FOR DISCUSSION • What are the options for 1st line therapy? • What is the optimal management of the elderly and the PS 2 patients? • What is the role of the non-platinum regimens? • What is the role of the molecular targeted agents in 1st line therapy?

  18. Non-Platinum Regimens • Deliver comparable survival with less toxicity better therapeutic index • Represent alternative regimens to patients who are not optimal candidates for platinum-based therapy

  19. Non-Platinum, Taxane-Based Doublets • Paclitaxel + gemcitabine • Docetaxel + gemcitabine • Paclitaxel + vinorelbine • Docetaxel + vinorelbine Non-Platinum, Non-Taxane Doublets • Vinorelbine + Gemcitabine • Gemcitabine + Irinotecan • Vinorelbine + Ifosfamide

  20. A EORTC Randomized Phase III Trial of Three Chemotherapy Regimens In Advanced Non-Small Cell Lung Cancer RANDOMIZED Paclitaxel 175 mg/m2 d 1 Cisplatin 80 mg/m2 d 1 every 21 days NSCLC PS 0-2 Stage IIIB or IV Gemcitabine 1250 mg/m2 d 1, 8 Cisplatin 80 mg/m2 d 1 every 21 days Gemcitabine 1250 mg/m2 d 1, 8 Paclitaxel 175 mg/m2 d 1 every 21 days Van Meerbeeck et al, Proc Am Soc Clin Oncol, 20: #1228, 2001

  21. Van Meerbeeck - Efficacy

  22. Van Meerbeeck - Toxicity

  23. GEMVIN – Study design Cisplatin 80 mg/ /m², d 1 Vinorelbine30 mg/m², d 1&8 or (at random) Cisplatin 80 mg/ /m², d 1 Gemcitabine 1200 mg/m², d 1&8 RANDOM Gemcitabine1000 mg/m², d 1&8 Vinorelbine25 mg/m², dd 1&8 Every 3 weeks, for a maximum of 6 cycles Gridelli, ASCO 2002

  24. GEMVIN – Progression-free survival

  25. GEMVIN – Overall survival

  26. Phase II Study of Vinorelbine-Gemcitabine vs Paclitaxel-Carboplatin RANDOMIZ A T I O N • Stratification • Stage IIIB/IV • PS 0−1/2 Vinorelbine 25 mg/m2 days 1, 8 Gemcitabine 1,000 mg/m2 days 1, 8 Paclitaxel 200 mg/m2 day1 Carboplatin (AUC=6) day 1 Primary endpoint: QoL analysis (LCSS) Every 3 weeks, for a maximum of 6 Cycles

  27. What is the role of the non-platinum regimens? • Taxane-based regimens appear to offer comparable efficacy to platinum-based combinations • Toxicity, however, is not significantly reduced and ca be substantial, especially in patients with less than optimal performance status • The non-platinum, non-taxane based regimens are less toxic, but questions about equivalent efficacy remain. They are a viable option for patients unable to tolerate platinum-based therapy

  28. QUESTIONS FOR DISCUSSION • What are the options for 1st line therapy? • What is the optimal management of the elderly and the PS 2 patients? • What is the role of the non-platinum regimens? • What is the role of the molecular targeted agents in 1st line therapy?

  29. Biological Agents for Solid Tumors Angiogenesis Inhibitors • SU5416/SU6668 • Anti-VEGF antibodies • Interferon-a/b • Marimastat • ZD6474 • LY317615 • TNP-470 • Endostatin/angiostatin Receptor-Targeted Therapy • Trastuzumab • Anti-EGFR • ZD1839 • C225 • OSI-774 Signal Transduction/Cell-Cycle Inhibitors • Farnesyl transferase • Flavopiridol • Retinoids • UCN-101 Gene Therapy • GM-CSF • Wild-type p53 • Antisense • c-myc • PKC Vaccines • Tumor cells • Peptides • Dendritic cells • Viral vaccines

  30. ZD1839 Randomized Trials With Chemotherapy in Advanced NSCLC Chemotherapy *x6 cycles + 250 mg ZD1839 Continue ZD1839 or placebo until disease progression Chemotherapy *x6 cycles Randomize + 500 mg ZD1839 Chemotherapy * x6 cycles + Placebo Stage III/IV NSCLC N=1029/Trial *Gemcitabine/cisplatin (trial 14) *Paclitaxel/carboplatin (trial 17) Primary endpoint: Survival

  31. R A N D O M I Z E CBDCA: AUC = 6 Paclitaxel: 200 mg/m2 • Eligibility: • No prior Rx • Stage IIIB or IV • Non-SqCCa • ECOG PS 0-1 CBDCA: AUC = 6 Paclitaxel: 200 mg/m2 rhuMAb-VEGF: 15 mg/kg Bevacizumab (rhuMAb-VEGF) in NSCLC:ECOG4599 Schema Upon PD crosssover to Anti-VEGF NOT ALLOWED

  32. The Affinitac Phase III Trial Eligible patientsrandomized to: ARM A ARM B Day 0: Paclitaxel 175 mg/m2 Carboplatin AUC 6 21-day cycle Days 0-14: ISIS 3521, CIV Day 3: Paclitaxel 175mg/m2Carboplatin AUC 6 Days 15-21: Rest Stratified for: Stage History of CNS Disease Restaging for response every 2 cycles Treatment continues up to 6 cycles (more if patient is benefiting) Sample size = 600 • Post-Treatment follow-up • Survival • Tumor progression

  33. What is the role of the molecular targeted agents in 1st line therapy?

More Related