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Hot topics in lung cancer: Adjuvant chemotherapy

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Hot topics in lung cancer: Adjuvant chemotherapy

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    1. Hot topics in lung cancer: Adjuvant chemotherapy ESMO Conference, Lugano 2007 Enriqueta Felip Vall dHebron University Hospital Barcelona, Spain

    4. Post-1995 meta-analysis adjuvant/platinum trials

    5. LACE Meta-analysis Randomized trials cisplatin-based vs no CT Sample size > 300 patients Five randomized trials / 4584 patients

    6. Adjuvant chemotherapy / stages Insufficient evidence for use with stage IA patients Retrospective analyses: IALT, greater benefit in stage IIIAN2 JRB.10, survival benefit in stage II; not in stage IB ANITA, survival benefit in stage II-III; not in stage IB CALGB 9633, negative study; survival benefit in T>4 cm Subset analyses should be viewed cautiously

    9. Adjuvant chemotherapy in NSCLC: standard approach Adjuvant cisplatin-based CT is recommended after complete resection in stage II-IIIA patients with good PS What can be done for patients? PS 2 Elderly patients With stage IB disease

    10. PS 2 patients enrolled ALPI NR IALT 7.3% JBR-10 0% ANITA 3%

    11. JBR-10: patients > 65 years Older patients received less chemotherapy Similar toxicities CT prolonged survival for elderly patients (HR=0.61) Despite receiving less CT, elderly patients derive a similar survival benefit from adjuvant CT Patients over 75 require further study (only 23 assessable patients)

    12. CALGB 9633 5-yr survival: 59% in CT arm vs 57% in control arm (HR, 0.80; p=0.10) Why was the CALGB study negative? Too few patients? Total accrual only 344 patients / initial accrual target 500 patients For an HR of 0.80 to be significant, over 1,000 patients required

    13. Is carboplatin inferior to cisplatin? Cisca meta-analysis (Ardizzoni et al, JNCI 07) 2968 patients (9 trials) randomized to cis or carbo Cis > carbo in RR (30% for cis; 24% for carbo) Overall, no significant differences in survival Subgroup analyses: cis > carbo in survival when combined with third generation agents and in non-squamous tumors Cisplatin-based chemotherapy: the cornerstone of adjuvant chemotherapy

    15. Adjuvant chemotherapy: lines of investigation Neoadjuvant vs adjuvant Integration new targeted drugs Customized adjuvant chemotherapy

    19. NATCH: preliminary findings in the neoadjuvant arm Survival data expected in 2009 203 patients included in the neoadjuvant arm: grade 3-4 neutropenia; 11% radiographic response; 59% complete resection rate; 94% pathologic complete response; 8.8% Neoadjuvant chemotherapy in early stage NSCLC has proven feasible and safe

    20. Phase III randomized trial of adjuvant chemotherapy with / without bevacizumab in completely resected stage IB-IIIA NSCLC (ECOG1505/BO19731)

    21. RADIANT: Erlotinib adjuvant trial

    22. Study design

    24. Molecular markers: predictive / prognostic factors in resected NSCLC

    26. Five-gene signature & clinical outcome Used both microarray analysis and RT-PCR to studied gene expression in frozen samples from 125 resected NSCLC patients 16 genes correlated with survival; selected 5 genes (DUSP6, MMD, STAT1, ERBB3, LCK) for RT-PCR and decision tree-analysis The 5 gene signature was an independent predictor of relapse and overall survival in 3 independent patient cohorts

    27. Molecular signatures in resected patients Potential clinical implications Prognosis assessment Objective; selection of patients for adjuvant CT: No adjuvant chemotherapy in patients with low-risk gene signature Adjuvant chemotherapy in patients with high-risk gene signature However predictive value of molecular signatures remains to be proven!

    28. Molecular signature profiles: comments Limitations associated with microarray techniques: Frozen samples Reproducibility Not yet standardized Molecular signatures should be validated in adjuvant therapy trials How to integrate molecular signatures with single gene prognostic and predictive markers should be explored

    29. Predictive markers in resected patients JBR. 10 adjuvant cis / vin benefit appears greater: in patients with high class III -tubulin (Seve et al, CCR 07) In patients with P53 IHC + (>15%) (Tsao et al, ASCO 07)

    30. IALT Bio (Olaussen et al, NEJM 06)

    34. Gene expression analysis was performed in frozen tumor samples from 126 completely resected Polish NSCLC patients.

    35. Adjuvant chemotherapy: summary Early-stage NSCLC, potentially curable after surgery, but with a wide spectrum of survival Adjuvant cisplatin-based CT, the standard of care in stage II-III The role of adjuvant chemotherapy for stage I remains controversial Integration of targeted agents in adjuvant setting

    36. Adjuvant chemotherapy: summary Gene expression profiles can identify patients with higher risk of recurrence (stage I disease) Molecular markers needed to guide customized treatment ERCC1; the most studied predictive marker, not yet validated in prospective trials Customized adjuvant CT, the way to go

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