1. 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,

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 ?
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ANY EVOLUTION IN CHEMOTHERAPY
OF NSCLC ?

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

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
ONE YEAR S %
MEDIAN OS ,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. 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 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: )

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. 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”

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

17. WHAT THE OPTIMAL DURATION OF CHEMOTHERAPY?
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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 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

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 nd 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 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

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

32. The 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 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