1 / 22

Novel Approaches in NSCLC Unresectable Stage IIIA/B Treatment

Explore the latest data on chemotherapy, radiation therapy, and targeted agents for unresectable NSCLC Stage IIIA/B. Key issues and key findings from ASCO 2007 and ASCO 2008 discussed in detail.

beauvais
Download Presentation

Novel Approaches in NSCLC Unresectable Stage IIIA/B Treatment

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. Post - ASCO 2007 Unresectable Stage IIIA/B NSCLC CONTENT • Take Home Message . . . . . 2 • Key Issues . . . . . . 4 • Chemotherapy and RT . . . . . 7 • Navelbine and RT . . . . . 15 • Targeted agents and RT. . . . . 18

  2. ASCO 08 NSCLC unresectable Stage IIIA/BTake Home Message • Many data on CT-RT without major results • Phases II with Taxanes, Pemetrexed • Integration of targeted agents (Cetuximab, Bevacizumab, Erlotinib) in concurrent CT-RT • Docetaxel as consolidation not recommended • Low MS with paclitaxel-CBDCA (known data…) • New data on NVB Oral and concurrent CT-RT • Focus on RT & CT-RT-induced toxicities (lung) (#7555p, #7573p, #7602p)

  3. ASCO 08 NSCLC unresectable Stage IIIA/BRT ant then… Induction, Sequential or Consolidation CT? • Induction CT beforeconcurrent CT-RT: • GEM-platin alone(#7599p)+ Taxane(#7589p) (#7592p) before D-platin-RT “limited impact on OS and PFS” or “GPG concurrently with GEM 225 mg/m2/wtoo toxic” but GEM-CDDP before CDDP-RT more favourable(#7558p) • Consolidation CT after concurrent CT-RT: • HOG LUN 01 update: docetaxel not recommended • GEM vs GEM-CBDCA(#7559p):no benefit from the combination (46 vs 42% 2y-OS) • GEM vs GEM-D after EP-RT(#7597p):better PFS for the doublet (24 vs 8 mo) but at the price of higher toxicity • Sequential CT: • Meta-analysis on 13 rando trials, 2776 pts (Bozcuk #7575p): • The shorter is the time to RT after the onset of induction CT, the greater is the benefit

  4. ASCO 08 NSCLC unresectable Stage IIIA/BKey Issues: Chemotherapy (1/2) • Docetaxel (D): • Ph III DP vs MVP with concur. RT(#7515p): benefit of 3rd generation CT • HOG-LUN 01 update (#7519p): refer to consolidation section • Weekly D in CT-RT schemes: • D-CDDP induction  wkly D-RT (#7561p): MS 21 mo & 2y OS 34% • D-CDDP induction  D-CDDP+concur. RT (#P 7585): 65% RR • Concurrent wkly D-CBDCA-RT (20 mg/m2, AUC 2, 60Gy)  consol. D-CBDCA (#7565p): 2y OS of 20%!, 21% G3 esophagitis & pneumonitis  scheme not recommended • Concurrent D-RT (20 mg/m2, #7581p): significant G3-4 tox. (20% esophagitis & 9% pneumonitis) + 5.5% related-death, MS 12.2mo • Paclitaxel-CDDP: sequential vs induction + RT (#7520p): • - Low median survival in both arms: 13.2 and 15.4 m • 3rd generation CT with CDDP–RT likely superior to 2nd generation • Unimproved outcome from taxanes as concurrent or consolidation CT in CT-RT

  5. ASCO 08 NSCLC unresectable Stage IIIA/BKey Issues: Chemotherapy (2/2) • Pemetrexed (PEM) : • Concurrent Pem-CDDP-RT  consol. D (#7569p): 53% RR • Pilot study of CBDCA + dose-dense Pem (#7571p) • Ph I concur. Pem-CDDP-RT(#7550p) • Other CT agents & concurrentRT: • S1 (Oral Fluoropyrim.) (Japan) + P + RT Ph II (#7556p): • 87% RR (46% IIIA), PFS 13.4 mo, 6% FN, 24% G3 neutropenia, 12% G3 esophagitis and 4% pneumonitis, • - Oral platinum (#7560p): MTD to be confirmed 30 mg /m2/d

  6. ASCO 08 NSCLC unresectable Stage IIIA/BKey Issues : Navelbine Oral/i.v. • Navelbine Oral is effective in elderly pts • 70 % ORR and 40% 2y-OS in “curative” intent (60 Gy RT) concurrent CT-RT setting (Silvano #20698p) • Navelbine iv or Oral: • A retrospective experience (Portalone #18507p)  Effective and safe concurrently with RT, even in elderly pts

  7. ASCO 08 NSCLC unresectable Stage IIIA/BKey Issues : Targeted Therapies • Cetuximab • Appears safe and promising when grafted onto various chemoradiation regimens (#7516p) (#7607p) • Bevacizumab and Erlotinib • Addition seems to be feasible but squamous histology requires major caution (pulmonary hemorrage G3-5)(#7517p) • Erlotinib added to RT, no convincing early results(#7563p)

  8. ASCO 2008Chemotherapy and RT

  9. Concomitant Docetaxel-CDDP vs MVP:A Japanese Phase III Experience (Kiura, #7515p*) # = N Abstract; O = Oral presentation; P = Poster; • 3rd generation CDDP based CT seems superior to 2nd generation cytotoxic • The MS and RR are related to the characteristics of Japanese population

  10. Concomitant Docetaxel-CDDP vs MVP:A Japanese Phase III Experience (Kiura, #7515p*) Toxicity G3-4 (% pts) # = N Abstract; O = Oral presentation; P = Poster; More esophagitis and treatment-related deaths in the DP-RT arm

  11. Consolidation Docetaxel:Survival update of HOG LUN – 01 (#Mina 7519p) # = N Abstract; O = Oral presentation; P = Poster; *DSMB = Data safety monitoring board Consolidation CT by TXT cannot be recommended

  12. Paclitaxel-platinum compound:Induction & concurrent scheme (Ardizzoni #7520p) # = N Abstract; O = Oral presentation; P = Poster; Poor survival results in both groups, in line with previous data withpaclitaxel

  13. Paclitaxel-platinum compound:Induction & concurrent scheme (Ardizzoni #7520p) Toxicity G3-4 (% pts) # = N Abstract; O = Oral presentation; P = Poster; Fewer additional toxicity in the concurrent scheme than the sequential one

  14. Gemcitabine CBDCA Induction:before CDDP + concurrent RT (Germonpré, #7558p) # = N Abstract; O = Oral presentation; P = Poster; Pre-Treatment FEV1 impacts on results: MS 21.6/9 mo if FEV1 70% /<70% And … Pneumonitis and eosophagitis are not reported !

  15. ASCO 2008:Navelbine and RT

  16. Navelbine Oral concurrently with RT in Elderly Stage IIIA/B NSCLC (Silvano, #20698p) • Oral VRB : 20mg/m2 twice weekly concurrently with RT • 25 pts > 65 y, ECOG < 2, Stage IIIA/B 30/70% • > 1 poor risk inclusion criteria: 60% • 10 pts received 60Gy as “curative” intent RT • 15 pts received 45Gy as palliative RT • Palliative RT: improvement of PS ECOG in 65% pts # = N Abstract; O = Oral presentation; P = Poster; • NBVo concurrently with 60 Gy RT effective in elderly population

  17. Navelbine concurrently with RT A retrospective analysis in Stage IIIA/B (Portalone P#18507) • 31 pts, 16 males, median age 60y, Stage IIIA/B 80.7/19.3% • Induction: CDDP 80 mg/ m2 or CBDCA AUC 5 plus either GEM 1200 mg/ m2 or NVBiv 25 mg/ m2 D1, 8, 21 • CT-RT: NVB iv 5 mg/ m2 or NVBo 12 mg/ m2 x 3 / week 2 hours before RT(2 Gy /d for 6 w) # = N Abstract; O = Oral presentation; P = Poster; • NVB concurrently with RT effective and safe

  18. ASCO 2008:Targeted Therapies and RT

  19. Erlotinib & concurrent 3D-RT vs 3D-RTRandomized Phase II-Efficacy (Martinez, #7563p*) Data updated since published abstract # = N Abstract; O = Oral presentation; P = Poster; • Erlotinib is safe & reported similar OR added to RT with OS not yet mature

  20. Cetuximab plus CT-RT (Paclitaxel-CBDCA):Ph. II RTOG 0324 -(Blumenschein #7516p*) Efficacy Toxicity G3-4 (% pts) # = N Abstract; O = Oral presentation; P = Poster; *Median FU: 21,6 mo Paclitaxel-CBDCA scheme & Cetuximab: MS not far from the doublet NVB-CDDP

  21. Cetuximab plus CT-RT (Paclitaxel-CBDCA):Randomized Phase II trial GALGB 30407– (Govindan, #7518p) Toxicity G3-4 (% pts) # = N Abstract; O = Oral presentation; P = Poster; Acceptable toxicities from the addition of Cetuximab

  22. Bevacizumab (B) + Erlotinib (E) plus CT-RT:Phase II trial – Toxicity G3-4(%pts) and ORR (Socinski, #7517p) # = N Abstract; O = Oral presentation; P = Poster; • The cohort II chosen for futher investigations (3 grade 3 lung toxicities) • Caution to lung hemorrage risks

More Related