1 / 37

CHEMOTHERAPY IN ADVANCED NSCLC

“If you have a long-distance patient with an advanced NSCLC, think it over before to treat him with chemotherapy.........” HANSEN, “personal communication” at European School of Oncology, 198. CHEMOTHERAPY IN ADVANCED NSCLC. Quali affermazione condivido circa la CT nel NSCLC.

emi-lynn
Télécharger la présentation

CHEMOTHERAPY IN 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. “If you have a long-distance patient with an advanced NSCLC, think it over before to treat him with chemotherapy.........” HANSEN, “personal communication” at European School of Oncology, 198............ CHEMOTHERAPY IN ADVANCED NSCLC

  2. Quali affermazione condivido circa la CT nel NSCLC • Nessun sostanziale progresso negli ultimi anni • L'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeutica • Stiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLC • Il PS gioca ancora un ruolo fondamentale Cross-tab label 24 / 30

  3. ANY EVOLUTION IN CHEMOTHERAPY OF NSCLC ? *****************

  4. There is an increasing number of abstr. about NSCLC in international meetings compared to SCLC : any progress in that disease ? In any case :

  5. THE POINTS: • What we know • Role of CDDP and del CBDCA • “two drugs” vs “three drugs” • Manteinance therapy • 2nd and 3rd line therapy • The matter of histology • The compromised PS • Chemotherapy in elderly

  6. WHAT WE KNOW: • So called “third generation” regimens have substantially similar efficacy • Different toxicity in different regimens • CDDP probably better than CBDCA

  7. Similar results with CDDP + DCT,PCT, Gem and CBDCA+ PCT • RR 24 - 30% • ONE YEAR S 37 - 39% • MEDIAN OS 8,6 – 9,1 m.

  8. DIFFERENT TOXICITY • More G4 leucop.:CDDP+DCT,VNB,GEM • More G4 thrombocytop.: CDDP+GEM • Better haemathologic.tol.: CBDCA+PCT • More alopecia: CDDP+DCT, CBDCA+PCT • CDDP more neurologic tox. than CBDCA • CDDP more emesis • Nephrotoxicity of CDDP • Use different regimens in different clinical setting......

  9. Efficacy similar but not identical (1) • OS: HR favours Gem (0.90): 1 year absolute benefit 3,9% - 2 years 2,6% • MS: 9 vs. 8,2 months • PFS: HR favours Gem (0.88): 1 year absolute benefit 4,2% • Med. PFS: 5,1 vs. 4,4 months • Le Chevalier, Lung Cancer 2005, 47:69-80

  10. CDDP+ “new drugs”: quite similar efficacy GEM and DTC containing regimen : better control of disease PTC containing regimen: significant increase of PD F.Grossi 12th World Conference on Lung Cancer Efficacy similar but not identical (2)

  11. Cis-Platin vs Carboplatin based chemotharapy in first-line treatment of advanced NSCLC : an individual patient data Meta-Analysis (A.Ardizzoni et al. J.Natl Cancer Inst 2007; 99: 847-57) Better CDDP or CBDCA? (1)

  12. Better CDDP or CBDCA ? (2)toxicity • Similar on WBC • Similar on HB • More on Platelets (CBDCA) • More gastrointestinal (CDDP) • More neurologic (CDDP)

  13. Better CDDP or CBDCA ? (3)efficacy • RR > CDDP : 30% vs 24% ( P < 0.001) • Risk of Death > CBDCA ( HR 1.07 vs 1.15) (P = NS) • > Risk of death (CBDCA) for non-squamous patients (HR 1.12, P = 0.02) when CDPP is combined with “new drugs”

  14. Better CDDP or CBDCA ? (4) • “Given the palliative nature of CT in adv. NSCLC and unquestionable pratical advantage of CBDCA in terms of ease of administartion, it could be argued that the small benefit achieved with CDDP relative to CBDCA, does not justify its preferential use in clinical pratice” • CDDP the European winner • CBDCA the American winner

  15. “ if the results of this meta-analysis may still support the use of CBDCA-based regimens in the palliative treatment of pts. with very advanced disease and/or poor PS, CDDP regimens may well be preferable in pts. whose PS is good and whose disease is less adv. (i.e. Oligomet. IV or III stage)” “CDDP should be remain the reference platinum agent for NSCLC at least in adv. disease with good prognosis and in those with earlier disease” Better CDDP or CBDCA ? (5)

  16. CDDP BASED REGIMENS WITH “NEW DRUGS” COULD BE THE STANDARD THERAPY Better CDDP or CBDCA ? (6)

  17. WHAT THE OPTIMAL DURATION OF CHEMOTHERAPY? ***************

  18. SMITH I.E. et al. (J.C.O. 2001) • Regimen : MVP • Duration : 3 vs 6 months • MST : 6 vs 7 months • 1 year survival : 22 vs 25% • Improvement symptoms : 67 vs 68% • COMMENTS : > fatigue, nausea and vomiting, = survival

  19. Socisky M.A. et al. (J.C.O. 2002) • Regimen : CBDCA + PCT • Duration : 4 cycles vs >PD • MST : 6.6 vs 8.5 months • 1 year survival : 28 vs 34 % • Similar QOL • No adv. for prolonged treat.

  20. Von Plessen C. et al. • Regimen : CDDP + VNR • Duration : 3 vs 6 cycles • MST : 28 vs 32 weeks • 1 year survival : 25 vs 25% • QOL : similar • No adv in RR and OS for 6 cycles

  21. Park JO et al. (J.C.O. 2007) • Regimen : CDDP + “3rd gen. Drugs” • Duration : 4 vs 6 cycles • MST : 15.9 vs 14.9 months • 1 year survival : 62.4 vs 59% • QOL : similar • Better TTP for 6 cycles

  22. Conclusions about duration,more chemoterapy : • Possible increase of TTP • More toxicity • Decrease of QOL • No better Survival • No better OS (Soon, Yu Yang et al. 12th World conference on Lung Cancer 2007)

  23. Three or two drugs in CDDP containing regimens ? • Three drugs : more RR (23 vs 31%) • No survival adv. • More toxicity (Delbaldo C et al JAMA 2004) • Comella et al. JCO 2000: CDDD/VNR/GEM vs CDDP/GEM : MST > 3 months for 3 drugs regimen • Three drugs better for neoadjuv ct ?

  24. Manteinance therapy :1) until PD2) Predefinite N° cycles • Ciuleanu T. (ASCO 2008) : manteinance Therapy with Pemetrexed in IIIb IV stage NSCLC : better PFS and better preliminary OS in non- squamous • Fidias P. (JCO 2009) : better PFS and NS improvement of OS when DCT administred immediately (max 6 cycles) vs delayed after front-line CDDP+ GEM ct

  25. 2nd line therapy : approved drugs • CHEMOTHERAPY: Docetaxel, Pemetrexed • EGFR TKI THERAPY: Gefitinib, Erlotinib • 2nd line therapy end-points: Symptom improvement, > TTP, > Disease Control, < Toxicity, > QOL VERY IMPORTANT TOPICS FOR 2nd LINE TREATMENT OF NSCLC

  26. Shepherd F. (J.C.O. 2000)Docetaxel vs BSC • Patients with PS 0 to 2 IIIb or IV stage after 1 or more CDDP containing regimens • Docetaxel 75mg/mt2 better than 100mg/mt2 • Median survival 7.5 vs 4.6 months • 1 year survival 37% vs 11% • At a dose of 75mg/mt2 benefits of Docetaxel outweigh risks

  27. Fossella F. (J.C.O. 2000)Docetaxel vs control (VNR or IFO) • Patients previous failed CDDP containing regimens • Docetaxel better than VNR or IFO control regimens • Docetaxel 75mg/mt2 less toxic than 100 • Previous exposure to Paclitaxel do not decrease likelihood of response to Docetaxel • > efficacy in CDDP resistant vs refractory • > TTP and PFS at 26 w in Docetaxel group • OS non significant better

  28. Docetaxel every 3w vs weekly(Meta-analysis) Di Maio M. (J.C.O. 2007) • “ weekly Docetaxel shows similar efficacy compared to 3 weeks Docetaxel and represents an alternative for 2nd line treatment of advanced NSCLC”

  29. Pemetrexed vs Docetaxel in 2nd lineHanna N. (J.C.O. 2004) • Pemetrexed 500mg/mt2 vs Docet 75mg/mt2 • RR 9.1% vs 8.8% (NS) • Pemetrexed : less G 3- 4 neutropenia, less febrile neutropenia, less hospitalization for febrile neutropenia, less G-CSF, less hospitalization for any drug-related AE

  30. 3rd line therapy ? • DEFINITION : patients previosly treated with CDDP containing regimen and Docetaxel or Pemetrexed • RR decreases with subsequent regimens of chemotherapy • Not clear evidence suporting 3rd line ct • Role for “biological” ? Target !!! • Importance of good PS and a low toxicity profile

  31. NSCLC vs SCLC ONCE UPON A TIME THERE WAS..........

  32. SQUAMOUS VS NON- SQUAMOUS..... The matter of histology........

  33. “The differential efficacy of pemetrexed according to NSCLC Histology: a review of two phase III studies” (Scagliotti, The Oncologist 2009) • A predictive role for NSCLC histology • Differential efficacy of Pemetrexed • Survival advantage for Pemetrexed in non squamous histology • Pemetrexed should be not recommended for the treatment of squamous cell ca. • May be preferable to other agents for non squamous NSCLC • A lower baseline TS expr. level may be an explanation for the > activity of P in non squamous histology

  34. And poor PS and elderly...? • Have a statistical advantage a clinical significance ? • Are the clinical trials well designed for elderly? • In elderly monoct probably best • CDDP containing ct could be considered in > 70y good PS • Monoct standard in PS2

  35. TAKE HOME MESSAGES • COMBINATION CDDP + 3rd GENERATION DRUG IS 1st CHOICE IN NON ELDERLY GOOD PS (“bulky disease ?”) • 3 DRUGS COMBINATION MORE ACTIVE BUT MORE TOXICITY • GEMCITABINE BEST TTP • PEMETREXED BEST IN NON SQUAMOUS • ELDERLY AND PS2 CONSIDER MONOCT

  36. Quali affermazione condivido circa la CT nel NSCLC • Nessun sostanziale progresso negli ultimi anni • L'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeutica • Stiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLC • Il PS gioca ancora un ruolo fondamentale

  37. Quali affermazione condivido circa la CT nel NSCLC • Nessun sostanziale progresso negli ultimi anni • L'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeutica • Stiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLC • Il PS gioca ancora un ruolo fondamentale Cross-tab label 0 / 0

More Related