Presentation on theme: "CHEMOTHERAPY IN ADVANCED NSCLC"— Presentation transcript:
1CHEMOTHERAPY 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,
2Quali affermazione condivido circa la CT nel NSCLC Nessun sostanziale progresso negli ultimi anniL'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeuticaStiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLCIl PS gioca ancora un ruolo fondamentaleCross-tab label24 / 30
3ANY EVOLUTION IN CHEMOTHERAPY OF NSCLC ? *****************ANY EVOLUTION IN CHEMOTHERAPYOF NSCLC ?
4In any case :There is an increasing number of abstr. about NSCLC in international meetings compared to SCLC : any progress in that disease ?
5THE POINTS: What we know Role of CDDP and del CBDCA “two drugs” vs “three drugs”Manteinance therapy2nd and 3rd line therapyThe matter of histologyThe compromised PSChemotherapy in elderly
6WHAT WE KNOW:So called “third generation” regimens have substantially similar efficacyDifferent toxicity in different regimensCDDP probably better than CBDCA
7Similar results with CDDP + DCT, PCT, Gem and CBDCA+ PCT ONE YEAR S %MEDIAN OS ,6 – 9,1 m.
8DIFFERENT TOXICITY More G4 leucop.:CDDP+DCT,VNB,GEM More G4 thrombocytop.: CDDP+GEMBetter haemathologic.tol.: CBDCA+PCTMore alopecia: CDDP+DCT, CBDCA+PCTCDDP more neurologic tox. than CBDCACDDP more emesisNephrotoxicity of CDDPUse different regimens in different clinical setting......
9Efficacy 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 monthsPFS: HR favours Gem (0.88): 1 year absolute benefit 4,2%Med. PFS: 5,1 vs. 4,4 monthsLe Chevalier, Lung Cancer 2005, 47:69-80
10Efficacy similar but not identical (2) CDDP+ “new drugs”: quite similar efficacyGEM and DTC containing regimen : better control of diseasePTC containing regimen: significant increase of PDF.Grossi 12th World Conference on Lung Cancer
11(A.Ardizzoni et al. J.Natl Cancer Inst 2007; 99: 847-57) 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: )
12Better CDDP or CBDCA ? (2) toxicity Similar on WBCSimilar on HBMore on Platelets (CBDCA)More gastrointestinal (CDDP)More neurologic (CDDP)
13Better 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”
14Better 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 winnerCBDCA the American winner
15Better 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”
16CDDP BASED REGIMENS WITH “NEW DRUGS” COULD BE THE STANDARD THERAPY Better CDDP or CBDCA ? (6)CDDP BASED REGIMENS WITH“NEW DRUGS” COULD BETHE STANDARD THERAPY
17WHAT THE OPTIMAL DURATION OF CHEMOTHERAPY? ***************WHAT THE OPTIMAL DURATION OFCHEMOTHERAPY?
18SMITH I.E. et al. (J.C.O. 2001) Regimen : MVP Duration : 3 vs 6 months MST : 6 vs 7 months1 year survival : 22 vs 25%Improvement symptoms : 67 vs 68%COMMENTS : > fatigue, nausea and vomiting, = survival
19Socisky M.A. et al. (J.C.O. 2002) Regimen : CBDCA + PCT Duration : 4 cycles vs >PDMST : 6.6 vs 8.5 months1 year survival : 28 vs 34 %Similar QOLNo adv. for prolonged treat.
20Von Plessen C. et al. Regimen : CDDP + VNR Duration : 3 vs 6 cycles MST : 28 vs 32 weeks1 year survival : 25 vs 25%QOL : similarNo adv in RR and OS for 6 cycles
21Park JO et al. (J.C.O. 2007) Regimen : CDDP + “3rd gen. Drugs” Duration : 4 vs 6 cyclesMST : 15.9 vs 14.9 months1 year survival : 62.4 vs 59%QOL : similarBetter TTP for 6 cycles
22Conclusions about duration, more chemoterapy : Possible increase of TTPMore toxicityDecrease of QOLNo better SurvivalNo better OS (Soon, Yu Yang et al. 12th World conference on Lung Cancer 2007)
23Three 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 regimenThree drugs better for neoadjuv ct ?
24Manteinance 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- squamousFidias 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
252nd line therapy : approved drugs CHEMOTHERAPY: Docetaxel, PemetrexedEGFR TKI THERAPY: Gefitinib, Erlotinib2nd line therapy end-points: Symptom improvement, > TTP, > Disease Control, < Toxicity, > QOL VERY IMPORTANT TOPICS FOR nd LINE TREATMENT OF NSCLC
26Shepherd F. (J.C.O. 2000) Docetaxel vs BSC Patients with PS 0 to 2 IIIb or IV stage after 1 or more CDDP containing regimensDocetaxel 75mg/mt2 better than 100mg/mt2Median survival 7.5 vs 4.6 months1 year survival 37% vs 11%At a dose of 75mg/mt2 benefits of Docetaxel outweigh risks
27Fossella F. (J.C.O. 2000) Docetaxel vs control (VNR or IFO) Patients previous failed CDDP containing regimensDocetaxel better than VNR or IFO control regimensDocetaxel 75mg/mt2 less toxic than 100Previous 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 groupOS non significant better
28Docetaxel 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”
29Pemetrexed vs Docetaxel in 2nd line Hanna N. (J.C.O. 2004) Pemetrexed 500mg/mt2 vs Docet 75mg/mt2RR 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
303rd line therapy ?DEFINITION : patients previosly treated with CDDP containing regimen and Docetaxel or PemetrexedRR decreases with subsequent regimens of chemotherapyNot clear evidence suporting 3rd line ctRole for “biological” ? Target !!!Importance of good PS and a low toxicity profile
31ONCE UPON A TIME THERE WAS.......... NSCLC vs SCLC
32The matter of histology........ SQUAMOUS VS NON- SQUAMOUS.....
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 histologyDifferential efficacy of PemetrexedSurvival advantage for Pemetrexed in non squamous histologyPemetrexed should be not recommended for the treatment of squamous cell ca.May be preferable to other agents for non squamous NSCLCA lower baseline TS expr. level may be an explanation for the > activity of P in non squamous histology
34And poor PS and elderly...?Have a statistical advantage a clinical significance ?Are the clinical trials well designed for elderly?In elderly monoct probably bestCDDP containing ct could be considered in > 70y good PSMonoct standard in PS2
35TAKE HOME MESSAGESCOMBINATION CDDP + 3rd GENERATION DRUG IS 1st CHOICE IN NON ELDERLY GOOD PS (“bulky disease ?”)3 DRUGS COMBINATION MORE ACTIVE BUT MORE TOXICITYGEMCITABINE BEST TTPPEMETREXED BEST IN NON SQUAMOUSELDERLY AND PS2 CONSIDER MONOCT
36Quali affermazione condivido circa la CT nel NSCLC Nessun sostanziale progresso negli ultimi anniL'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeuticaStiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLCIl PS gioca ancora un ruolo fondamentale
37Quali affermazione condivido circa la CT nel NSCLC Nessun sostanziale progresso negli ultimi anniL'importante è separare NSCLC da SCLC, la specifica istologia del NSCLC non ha molto peso nella scelta terapeuticaStiamo andando verso terapie diversificate a seconda dell' istologia anche nel caso del NSCLCIl PS gioca ancora un ruolo fondamentaleCross-tab label0 / 0