New Trends & Current Research in the Treatment of Lung Cancer, Pt. II

Transcription

1 New Trends & Current esearch in the Treatment of Lung Cancer, Pt. II Howard (Jack) West, MD President & CEO, GACE Medical Director, Thoracic Oncology Program Swedish Cancer Institute Seattle, WA Cancer Lifeline Seattle, WA May 2, 2 Disclaimers The information provided here includes views of the presenter that do not necessarily represent those of the Global esource for Advancing Cancer Education (GACE) in general, nor those of Swedish Cancer Institute. The contents of this program do not constitute medical advice and is intended to supplement but not replace input from an individual patient s medical team.

2 Early Stage (esectable) Non-Small Cell Lung Cancer Clinical/Pathologic Staging of NSCLC (Mountain, Chest :7, 7) 5-year Survival, Clinical Staging 5-year Survival, Path/Surg Staging T N T2 N T N T2 N T N T N T- N2 6% 8% 4% 24% 22% % % 67% 57% 55% % 8% 25% 2% Distant failures in 5-7% in most studies, respresenting micrometastatic disease Even early stage NSCLC is a systemic ( whole body ) disease

3 B. - Study Design T-2, N- NSCLC N2 nodes sampled N = 482 Stratified by: N vs N as pos, neg, or unknown A N D O M I Z E D Cisplatin 5 mg/m2 d, 8 Vinorelbine 25 mg/m2/wk x 4 No chemotherapy Winton, NEJM 52:2582, 25 B.: Efficacy esults N = 482 pts 4 Ineligible Median Survival N = 24 4 months (P =.2) H.7 Observation N = 2 7 months 5-Year Survival 6% (P =.2) H.7 54% PFS Not reached (P =.4) 46.7 months

4 B. Survival Curves Winton, NEJM 52:2582, 25 B. Survival Curves by Stage Winton, NEJM 52:2582, 25

5 LACE Meta-Analysis: Effect & Stage Category No. Deaths / No. Entered Hazard ratio ( / Control) H [5% CI] Stage IA 2 / 47.4 [.6;2.] Stage IB 5 / 7.2 [.78;.] Stage II 88 / 66.8 [.7;.5] Stage III 865 / [.7;.5] better Control better Test for trend: p =.5 Chemo may be detrimental for stage IA, but stage IA patients were generally not given the potentially best combination cisplatin/vinorelbine (% of stage IA patients versus ~4% for other stages) Pignon, Proc ASCO pts. (28 centers,4 countries) evaluable for ECC expression ECC repairs cisplatin-dna adducts, so expression indicates platinum resistance ECC a double-edged sword ; worse prognosis of NSCLC if low expression, but more responsive to platinum 5 5

6 Overall Survival by ECC- Expression ECC-Negative Tumors ECC-Positive Tumors O ve ra ll S u rv iva l % 8% 6% 4% 2% % No at risk Control 2 Years Control 6 2 Adjusted H =.65 5% PI [.5-.86], p = Overall Survival No at risk % 8% 6% 4% 2% Control % 2 Years Control Adjusted H =.4, 5% CI [ ], p = Olaussen, NEJM 26 5-gene Signature is Prognostic in Stage I and Stage II Patients Stage IB (n=4) Stage II (n=28) Percentage Percentage No. at isk Low isk 2 High isk 4 High risk 6 Low risk 6 Time (Years) High risk Low risk 6 Time (Years) 7 H.2 (5% CI ) p<. Tsao, Proc ASCO 28, A#75 H.47 (5% CI.-6.4) p<.

7 Benefits JB. High isk but Not Low isk Patients JB., high risk (n=67) JB., low risk (n=66) 8 Percentag e 6 4 Percentage No. at isk Observ. Chemo 2 Chemo Observation 6 Time (Years) H. (5% CI.7-.6) p=.5 Tsao, Proc ASCO 28, A# Chemo H.67 (5% CI.22-.6) p=. Interaction p =. Observation 6 Time (Years) Gene Signature for Prognosis of Adjuvant Chemo Candidates: Conclusions 5 gene signature may refine prognosis with implications on choice of adjuvant chemotherapy Need further validation by prospectively before incorporation into standard of care equirement of snap frozen tissue limits generalizability Tsao, Proc ASCO 28, A#75

8 ECOG 55/Intergroup Adjuvant Trial PI Heather Wakelee NSCLC s/p surgery Stage IB (>4 cm only) Stage II Stage III (Non-N2) A N D O M I Z E Primary endpoint: Overall Survival Cisplatin-based chemo cisplatin-vinorelbine cisplatin-gemcitabine cisplatin-docetaxel cisplatin-pemetrexed (non-squamous) Cisplatin-based chemo cisplatin-vinorelbine cisplatin-gemcitabine cisplatin-docetaxel cisplatin-pemetrexed (non-squamous) + bevacizumab 5 mg/kg qwk andomized Double-blind trial In Adjuvant NSCLC with Erlotinib (ADIANT) N = 45 patients St IB. IIIA NSCLC EGF positive (IHC and/or FISH) No Chemo or up to 4 cycles of std platinum-based, adjuvant chemo A N D O M I Z E 2 Erlotinib 5 mg daily Placebo 2yrs or until one of the following: elapse Death Pt request Investigator decision Intolerable toxicity Follow up visit Q 6 months X 5 years, then yearly PI Dr. Karen Kelly

9 andomized Phase III Study Design - MAGIT esectable MAGE-A+ NSCLC Surgery Pathological stage IB, II, IIIA No chemotherapy Up to 4 cycles platinum based chemotherapy MAGE-A ASCI Placebo MAGE-A ASCI Placebo Powered for efficacy Powered for efficacy (My) Current Conclusions on Systemic Therapy for Early Stage NSCLC Clinically, statistically significant OS benefit w/platinum doublet in stage II-IIIA Would now generally recommend cisplatin-based doublet when feasible Stage IB treatment may still be individualized Some evidence for giving chemo for larger but not smaller IB tumors However, recent work suggests small but real long-term mortality risk: patients with less to gain from chemo (by stage or molecular criteria) may be harmed Molecular selection based on ECC, gene signature, etc. may help us refine predicted benefits much better; requires much more corroborative work Current questions: role of Avastin? EGF inhibitors? Vaccinebased therapy? These data apply to a disproportionately young, good PS population, not to everyone