1 / 36

Targeted Therapies in Advanced NSCLC: Insights from Clinical Trials

Explore three treatment strategies in advanced non-small cell lung cancer combining chemotherapy and EGFR inhibitors, based on clinical trial results and patient endpoints.

christophercalderon
Download Presentation

Targeted Therapies in Advanced NSCLC: Insights from Clinical Trials

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. CHEMO-IMMUNO-TARGET THERAPIES Tre strategie di trattamento nel NSCLC in stadio avanzato Camogli, 29-30 Aprile 2016 Gliinibitori di EGFR in associazioneallachemioterapianeipazienti wild-type Erika Rijavec UOS Tumori Polmonari Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro Genova

  2. EGFR pathway

  3. TALENT and TRIBUTE Trials TALENT (N=1059): CDDP 80mg/mq gg1 + gemcitabine 1250 mg/mq gg1,8 q21 TRIBUTE (N=1172): CBDCA AUC 6 gg1 + paclitaxel 200 mg/mq gg1, q21 Gatzemeier U, JCO 2007; Herbst RS, JCO 2005

  4. TALENT Results TTP OS Gatzemeier U, JCO 2007

  5. TRIBUTE Results OS TTP Herbst RS, JCO 2005

  6. INTACT 1 Trial CDDP + GEM 3 wkly for 6 cycles + GEFITINIB 250 mg until PD CDDP + GEM 3 wkly for 6 cycles + GEFITINIB 500 mg until PD Endpoints Patients (N=1093) • Age ≥18 years • PS 0-2 • Stage IIIB/IV • No previous chemotherapy Primary • Overall survival Secondary • Response rate • Time to progression • Safety evaluation CDDP + GEM 3 wkly for 6 cycles + placebo until PD Giaccone G, JCO 2004

  7. INTACT 1 Trial: Results OS: G250 9.9 m G500 9.9 m Placebo 10.9 m (P=.460) TTP: G250 5.8 m G500 5.5 m Placebo 6.0 m (P=.76) RR: G250 50.3 % G500 49.7 % Placebo 44.8 %

  8. INTACT 2 Trial CBDCA AUC 6 + paclitaxel for 6 cycles + GEFITINIB 250 mg until PD CBDCA AUC 6 + paclitaxel for 6 cycles + GEFITINIB 500 mg until PD Endpoints Patients (N=1037) • Age ≥18 years • PS 0-2 • Stage IIIB/IV • No previous chemotherapy Primary • Overall survival Secondary • Response rate • Time to progression • Safety evaluation CBDCA AUC 6 + paclitaxel for 6 cycles + placebo until PD Herbst RS, JCO 2004

  9. INTACT 2 Trial: Results OS: G250 9.8 m G500 8.7 m Placebo 9.9 m (P=.64) TTP: G250 5.3 m G500 4.6 m Placebo 5.0 m (P=.0562) RR: G250 30.4 % G500 30 % Placebo 28.7 %

  10. Potential antagonism CT + EGFR TKI Tumorcellsweredriven to G0/G1 phase by EGFR TKI while CT usuallyworks best in the mitoticphase

  11. First-line Asian Sequential Erlotinib plus chemo trial (FAST-ACT) Platinum (d1) Gemcitabine (d1, 8) + Erlotinib D15-28 Q4weeks x 6 cycles Erlotinib Untreated NSCLC IIIB/IV No prior EGFR TKI (N=154) 1:1 Platinum (d1) Gemcitabine (d1, 8) + Placebo D15-28 Q4weeks x 6 cycles Placebo Primary endpoint: NPR at 8 w Secondary endpoints: NPR at 16 w, RR, PFS, OS, duration of response, safety Mok T, JCO 2009

  12. FAST-ACT Results PFS NPR no difference (80.3% vs 76.9%) Mok T, JCO 2009

  13. FAST-ACT 2 Study Design Gemcitabine 1,250mg/m2 (d1, 8) + carboplatin AUC=5 or cisplatin 75mg/m2 (d1) + erlotinib 150mg/day (d15–28); q4wks x 6 cycles GC-erlotinib (n=226) Erlotinib 150mg/day PD Previously untreated stage IIIB/IV NSCLC, PS 0/1 (n=451) 1:1; stratified by stage, histology, smoking status and chemo regimen Gemcitabine 1,250mg/m2 (d1, 8) + carboplatin AUC=5 or cisplatin 75mg/m2 (d1) + placebo (d15–28); q4wks x 6 cycles GC-placebo (n=225) Placebo PD Primary endpoint: PFS Wu YL, Lancet 2013

  14. FAST-ACT 2 Results HR=0.57 (95% CI 0.47–0.69) p<0.0001 HR=0.79 (95% CI 0.64–0.99) p=0.0420 Wu YL, Lancet 2013

  15. PFS and OS in EGFR WT subgroup PFS OS 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 GC-erlotinib (n=69) GC-erlotinib (n=69) GC-placebo (n=67) GC-placebo (n=67) HR=0.97 (0.69–1.36) p=0.8467 RR: 26.1% vs 19.4% HR=0.77 (0.53–1.11) p=0.1612 OS probability PFSprobability 12.2 14.9 5.9 6.7 0 4 8 12 16 20 24 28 32 36 40 0 4 8 12 16 20 24 28 32 36 40 Time (months) Time (months)

  16. PFS and OS in EGFR mut subgroup PFS OS 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 GC-erlotinib (n=49) GC-erlotinib (n=49) GC-placebo (n=48) GC-placebo (n=48) HR=0.25 (0.16–0.39) p<0.0001 RR: 83.7% vs 14.6% HR=0.48 (0.27–0.84) p=0.0092 OS probability PFSprobability 6.9 16.8 20.6 31.4 0 4 8 12 16 20 24 28 32 0 4 8 12 16 20 24 28 32 36 Time (months) Time (months)

  17. Cetuximab • Recombinant human/mouse IgG1 monoclonal antibody • Specifically binds to the EGFR with higher affinity than its natural ligands (TGFa, EGF) • Induce apoptosis and ADCC1 • Preclinical synergistic activity in combination with chemotherapy and radiotherapy

  18. FLEX Study Design N=1125 Primary endpoint: OS Secondary endpoints: PFS, ORR, quality of life, safety Pirker R, Lancet 2009

  19. FLEX Study Results OS: 11.3 m vs 10.1 m (P= 0.044) Pirker R, Lancet 2009

  20. FLEX Adverse Events Pirker R, Lancet 2009

  21. Survival according EGFR expression Low EGFR expression P=0.88 Hight EGFR expression P=0.011 Pirker R, Lancet 2012

  22. BMS099 Study 1:1 N=676 Primary endpoint: PFS-IRRC Secondary endpoints: OS, ORR, quality of life, safety Lynch TJ, JCO 2010

  23. BMS099 Study Results: PFS IRRC Lynch TJ, JCO 2010

  24. Meta-analysis OS: 10.3 m vs 9.4 m (P=0.009) PFS: 4.7 m vs 4.5 m (P=0.045) Pujol JL, Lung Cancer 2014

  25. Necitumumab

  26. INSPIRE: Study Design N=633 Primary endpoint: OS Secondary endpoints: PFS, ORR, TTF, safety, immunogenicity of necitumumab, EGFR protein expression Paz-Ares L, Lancet 2015

  27. INSPIRE: Results OS: 11.3 m vs 11.5 m (P= 0.96) PFS: 5.6 m vs 5.6 (P= 0.96) High EGFR expression was associated to better outcomes in both treatment arms Paz-Ares L, Lancet 2015

  28. INSPIRE: Toxicity Paz-Ares L, Lancet 2015

  29. Squire: Study Design N=1093 Primary endpoint: OS Secondary endpoints: PFS, ORR, TTF, health status, immunogenicity of necitumumab, safety, pharmacokinetics Thatcher N, Lancet 2015

  30. Squire: Results OS: 11.5 m vs 9.9 m (P= 0.01) PFS: 5.7 m vs 5.5 m (P= 0.02) Thatcher N, Lancet 2015

  31. Squire: Subgroup Analysis Thatcher N, Lancet 2015

  32. Squire: Adverse Events Thatcher N, Lancet 2015

  33. EGFR expression Thatcher N, Lancet 2015

  34. Grazie per l’attenzione!

More Related