Presentation on theme: "CHEMOTHERAPY IN ADVANCED NSCLC If you have a long-distance patient with an advanced NSCLC, think it over before to treat him with chemotherapy........."— Presentation transcript:
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,
Quali affermazione condivido circa la CT nel NSCLC 24 / 30 Cross-tab label 1.Nessun sostanziale progresso negli ultimi anni 2.L'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeutica 3.Stiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLC 4.Il PS gioca ancora un ruolo fondamentale
***************** ANY EVOLUTION IN CHEMOTHERAPY OF NSCLC ?
In any case : There is an increasing number of abstr. about NSCLC in international meetings compared to SCLC : any progress in that disease ?
THE POINTS: What we know Role of CDDP and del CBDCA two drugs vs three drugs Manteinance therapy 2 nd and 3 rd line therapy The matter of histology The compromised PS Chemotherapy in elderly
WHAT WE KNOW: So called third generation regimens have substantially similar efficacy Different toxicity in different regimens CDDP probably better than CBDCA
Similar results with CDDP + DCT, PCT, Gem and CBDCA+ PCT RR % ONE YEAR S % MEDIAN OS 8,6 – 9,1 m.
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......
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
Efficacy similar but not identical (2) CDDP+ new drugs: quite similar efficacy GEM and DTC containing regimen : better control of disease PTC containing regimen: significant increase of PD F.Grossi 12 th World Conference on Lung Cancer
Better CDDP or CBDCA? (1) 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: )
Better CDDP or CBDCA ? (2) toxicity Similar on WBC Similar on HB More on Platelets (CBDCA) More gastrointestinal (CDDP) More neurologic (CDDP)
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
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
Better CDDP or CBDCA ? (5) 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 ? (6) CDDP BASED REGIMENS WITH NEW DRUGS COULD BE THE STANDARD THERAPY
*************** WHAT THE OPTIMAL DURATION OF CHEMOTHERAPY?
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
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.
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
Park JO et al. (J.C.O. 2007) Regimen : CDDP + 3 rd 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
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. 12 th World conference on Lung Cancer 2007)
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 ?
Manteinance therapy : 1) until PD 2) 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
2 nd line therapy : approved drugs CHEMOTHERAPY: Docetaxel, Pemetrexed EGFR TKI THERAPY: Gefitinib, Erlotinib 2 nd line therapy end-points: Symptom improvement, > TTP, > Disease Control, QOL VERY IMPORTANT TOPICS FOR 2 nd LINE TREATMENT OF NSCLC
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
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
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 2 nd line treatment of advanced NSCLC
Pemetrexed vs Docetaxel in 2 nd line Hanna 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
3 rd 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 3 rd line ct Role for biological ? Target !!! Importance of good PS and a low toxicity profile
ONCE UPON A TIME THERE WAS NSCLC vs SCLC
The matter of histology SQUAMOUS VS NON- SQUAMOUS.....
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
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
TAKE HOME MESSAGES COMBINATION CDDP + 3 rd GENERATION DRUG IS 1 st 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
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
Quali affermazione condivido circa la CT nel NSCLC 0 / 0 Cross-tab label 1.Nessun sostanziale progresso negli ultimi anni 2.L'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeutica 3.Stiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLC 4.Il PS gioca ancora un ruolo fondamentale