A paradigm shift in the treatment of advanced lung cancer: survival and symptom benefits with Tarceva Tudor-Eliade Ciuleanu Cancer Institute Ion Chiricuta.

Slides:



Advertisements
Similar presentations
IDEAL 1 and IDEAL 2.
Advertisements

Treatment in Advanced Non-Small Cell Lung Cancer.
PARAMOUNT: phase III study of pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC.
Non-small Cell Lung Cancer
Paz-Ares LG et al. Proc ASCO 2011;Abstract CRA7510.
Questions and answers about PARAMOUNT: phase III study of pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC.
A Phase III Randomized, Double-Blind, Placebo-Controlled Trial of the Epidermal Growth Factor Receptor Inhibitor Gefitinb in Completely Resected Stage.
Have the OPTIMOX-2, CAIRO-3, COIN, DREAM and other recent trials settled the question of maintenance versus observation in advanced CRC? Yes Deborah Schrag,
Robertson JFR et al. J Clin Oncol 2009;27(27):
Herceptin® (trastuzumab) in combination with chemotherapy: pivotal metastatic breast cancer survival data 1.
Presented by Martin H. Cohen, M.D. at the 27 July 2004 meeting of the Oncologic Drugs Advisory Committee.
CRC-1 The Need for 3rd-Line Therapy in Non-Small Cell Lung Cancer Frances A. Shepherd, MD Scott Taylor Chair in Lung Cancer Research Princess Margaret.
Phase III Study Comparing Gemcitabine plus Cetuximab versus Gemcitabine in Patients with Locally Advanced or Metastatic Pancreatic Adenocarcinoma Southwest.
First-Line TKI Use in EGFR Mutation-Positive NSCLC
A Phase III, Randomized, Double-Blind, Placebo-Controlled Registration Trial to Evaluate the Efficacy and Safety of Placebo + Trastuzumab + Docetaxel vs.
Taxane-pretreated metastatic breast cancer (MBC): investigational agents TTP = median time to disease progression OS = median overall survival.
Phase III studies of Xeloda® in colorectal cancer (CRC)
Thymidine phosphorylase (TP) upregulation Dose- and time-dependent upregulation of TP in human colon cancer xenografts PaclitaxelDocetaxel.
Please note, these are the actual video-recorded proceedings from the live CME event and may include the use of trade names and other raw, unedited content.
Capecitabine versus Bolus 5-FU/Leucovorin as Adjuvant Therapy for Colon Cancer: X-ACT Trial Results James Cassidy, MD Colorectal Cancer Update Think Tank.
Lung cancer perspectives. Targeted therapy : one for all or a few for one ? Miklos Pless, Winterthur
Herceptin ® : leading the way in metastatic breast cancer care Steffen Kahlert.
This house believes that FOLFIRINOX is the best treatment for patients with metastatic pancreatic adenocarcinoma Pro Marc YCHOU Montpellier.
Axel Grothey, MD Professor of Oncology Mayo Clinic Rochester, Minnesota Strategies to Improve Patient Outcomes in Gastric and Gastroesophageal Junction.
Xeloda ® monotherapy in pancreatic cancer: phase II study  42 patients with advanced/metastatic pancreatic cancer received intermittent Xeloda 1,250mg/m.
CE-1 IRESSA ® Clinical Efficacy Ronald B. Natale, MD Director Cedars Sinai Comprehensive Cancer Center Ronald B. Natale, MD Director Cedars Sinai Comprehensive.
Randomized Phase III Trial Comparing FOLFIRINOX (F: 5FU/Leucovorin [LV], Irinotecan [I], and Oxaliplatin [O]) versus Gemcitabine (G) as First-Line Treatment.
 Angiogenesis Signaling Cascades EGFR PI3K MAPK Nucleus Gene Activation Cell Cycle Progression M G1G1 S G2G2 Fos P P MAPK = mitogen-activated protein.
Romàn Pérez-Soler Gutman Professor of Medicine and Chairman of the Department of Oncology at the Montefiore Medical Center, Albert Einstein College of.
Quality of life results from a Phase III trial of trastuzumab plus chemotherapy in first-line HER2-positive advanced gastric and GE junction cancer Taroh.
Riyaz Shah Kent Oncology Centre Maidstone, UK ErbB family blockade in squamous cell carcinoma (SCC): Latest clinical understanding.
REVISIÓN ESTADIOS IV SEGUNDA LÍNEA “WILD TYPE” Sergio Vázquez Estévez Servicio Oncoloxía Médica Hospital Universitario Lucus Augusti. Lugo Baiona, 25 Abril.
KRAS status and efficacy in the first- line treatment of patients with mCRC treated with FOLFOX with or without cetuximab: The OPUS experience Carsten.
Final Efficacy Results from OAM4558g, a Randomized Phase II Study Evaluating MetMAb or Placebo in Combination with Erlotinib in Advanced NSCLC Spigel DR.
AVADO TRIAL David Miles Mount Vernon Cancer Centre, Middlesex, United Kingdom A randomized, double-blind study of bevacizumab in combination with docetaxel.
Cmab might have therapeutic benefit in Japanese patients with KRAS p.G13D mutant colorectal cancer. Limitations of this study are its retrospective design.
SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following non-progression with 1st-line platinum-based chemotherapy.
Overall survival in NSCLC
Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer: the influence of KRAS and BRAF biomarkers on outcome: updated data from the CRYSTAL.
GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma [HCC] and Of its treatment with sorafeNib) second interim analysis in.
CV-1 Trial 709 The ISEL Study (IRESSA ® Survival Evaluation in Lung Cancer) Summary of Data as of December 16, 2004 Kevin Carroll, MSc Summary of Data.
CB-1 Background of Pancreatic Cancer & NCIC CTG PA.3 Study Design Malcolm Moore, MD Professor of Medicine and Pharmacology Princess Margaret Hospital Chair,
CD-1 Second-line Chemotherapy for Hormone Refractory Prostate Cancer Disease Background Nicholas J. Vogelzang, MD Director Nevada Cancer Institute CD-1.
CALYPSO Trial: Carboplatin & Pegylated Liposomal Doxorubicin (PLD) versus Carboplatin & Paclitaxel in Relapsed, Platinum- Sensitive Ovarian Cancer Pujade-Lauraine.
Impact of Bevacizumab (Bev) on Efficacy of Second-Line Chemotherapy (CT) for Triple- Negative Breast Cancer: Analysis of RIBBON-2 Brufsky A et al. Proc.
Low Dose Decitabine Versus Best Supportive Care in Elderly Patients with Intermediate or High Risk MDS Not Eligible for Intensive Chemotherapy: Final Results.
1 A Randomized, Multi-Center Phase III Trial of Irinotecan in Combination with Three Different Methods of Administration of Fluoropyrimidine with Celecoxib.
Moskowitz CH et al. Proc ASH 2014;Abstract 673.
A Phase III, Open-Label, Randomized, Multicenter Study of Eribulin Mesylate versus Capecitabine in Patients with Locally Advanced or Metastatic Breast.
Personalized medicine in lung cancer R4 김승민. Personalized Medicine in Lung Cancer patients with specific types and stages of cancer should be treated.
Mok TS, Wu SL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361: Gefitinib Superior.
Erlotinib plus Gemcitabine Compared with Gemcitabine Alone in Patients with Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute.
Esophageal Cancer: A Critical Evaluation of Systemic Second-Line Therapy Christiane Maria Rosina Thallinger, Markus Raderer, and Michael Hejna J Clin Oncol.
J Thorac Oncol. 2012;7: 1653–1660) David P. Carbone, MD, PhD,* Keyue Ding, PhD,† Heinrich Roder, PhD,‡ Julia Grigorieva, PhD,‡ Joanna Roder, PhD,‡ Ming-Sound.
Weekly Paclitaxel Combined with Monthly Carboplatin versus Single-Agent Therapy in Patients Age 70 to 89: IFCT-0501 Randomized Phase III Study in Advanced.
1 LUX-Lung 3 clinical trial ECOG=Eastern Cooperative Oncology Group. Sequist LV et al. J Clin Oncol. 2013;31(27): Treatment-naïve Advanced NSCLC.
CCO Independent Conference Coverage
Belani CP et al. ASCO 2009; Abstract CRA8000. (Oral Presentation)
LUX-Lung 6 clinical trial
LUX-Lung 3 clinical trial
ASPEN: Prolonged PFS With Sunitinib vs Everolimus in Nonclear-Cell RCC CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* May 29 -
Maintenance Lapatinib After Chemotherapy in HER1/2-Positive Metastatic Bladder Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
Outcomes of patients in the North Trent region with advanced non-small-cell lung cancer treated with maintenance pemetrexed following induction with platinum.
What do we do after FOLFIRINOX? Gemcitabine-Based Therapy is Standard
Improved Survival With Nivolumab vs Docetaxel in Pts With Advanced Squamous Cell NSCLC After Platinum-Containing Chemotherapy: CheckMate 017 Slideset on:
Elotuzumab, Lenalidomide, and Low-Dose Dexamethasone in Relapsed/Refractory Myeloma Slideset on: Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in combination.
(NCIC CTG) and the Australasian Gastro-Intestinal Trials Group (AGITG)
Maintenance paradigm in non-squamous NSCLC
Controversias de Temas de Actualidad: ¿Sería Necesario Modificar el Desarrollo Clínico de los Nuevos Fármacos? a Favor Manuel Hidalgo, M.D., Ph.D.
Phase II trial of erlotinib in advanced pancreatic cancer
Presentation transcript:

A paradigm shift in the treatment of advanced lung cancer: survival and symptom benefits with Tarceva Tudor-Eliade Ciuleanu Cancer Institute Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu Cluj-Napoca, Romania

What are our therapeutic objectives in advanced NSCLC? To prolong life –improved survival –lengthened time to disease progression To maintain QoL –improved disease-related symptoms/QoL To develop better-tolerated treatment regimens QoL = quality of life

More effective and better tolerated second-line therapeutic strategies are needed Increasing need for second-line treatment due to greater use of first-line, platinum-based chemotherapy Many patients (e.g. elderly, poor PS) are unsuitable to receive chemotherapy due to significant toxicities Patients progressing on first-line chemotherapy may benefit from an agent with a different mechanism of action As single agents, docetaxel and pemetrexed have proven benefits in second-line NSCLC, but are limited by significant toxicities

Tarceva: preliminary evidence of antitumour effects and clinical benefits Objective RR = 12.3% (5.1–23.7) Median OS = 8.4 months (4.8–13.9) 1-year survival rate = 40% (28–54) Survival distribution function Time (months) Pérez-Soler R, et al. J Clin Oncol 2004;22:3238–47 Phase II trial in relapsed NSCLC: overall survival OS = overall survival RR = response rate Tarceva 150mg/day

BR.21, a randomised phase III trial of Tarceva (erlotinib; OSI-774) as treatment following chemotherapy in patients with advanced NSCLC: an NCIC CTG trial NCIC CTG = National Cancer Institute of Canada Clinical Trials Group

BR.21: study design PS = performance status; CR = complete response; PR = partial response SD = stable disease; PD = progressive disease Stratified by: Centre PS (0/1 vs 2/3) Response to prior treatment (CR/PR:SD:PD) Prior regimens (1 vs 2) Prior platinum (yes vs no) Tarceva 150mg daily Placebo 2 1 R A N D O M I S E

BR.21: patient characteristics

NCIC CTG BR.21: best response (n=638)* CI = confidence interval *Measurable disease was not an entry criterion

*HR and p (log-rank test) adjusted for stratification factors at randomisation and HER1/EGFR status BR.21: improvement in overall survival with Tarceva 42.5% improvement in median survival Survival distribution function Survival time (months) HR=0.73, p<0.001* Shepherd F, et al. N Engl J Med 2005;353:123–32 Tarceva Placebo

Forest plot of survival by subsets D-R = diagnosis to randomisation HR <1 = improved survival with Tarceva Tarceva:placebo PS 0–1 PS 2–3 Male Female <65 years  65 years Adenocarcinoma Squamous type Other histology Prior weight loss <5% Prior weight loss 5–10% Prior weight loss >10% Never-smoker Current/ex-smoker 1 prior regimen 2+ prior regimens HR Factors Tarceva:placebo Prior platinum No prior platinum Prior taxane No prior taxane Best prior response: CR/PR Best prior response: SD Best prior response: PD D-R: <6 months D-R: 6–12 months D-R: >12 months HER1/EGFR-positive HER1/EGFR-negative HER1/EGFR-unknown Canada/USA Rest of world HR Tarceva ® Prescribing Information OSI Pharmaceuticals, Inc., and Genentech, Inc.

Survival benefit with erlotinib according to HER1/EGFR biomarker status nHRCIp* p†p† Mutation status Wild-type – Mutant – EGFR expression (IHC) IHC – IHC– – Gene copy Number (FISH) Low – High – *p value for subgroup compared with placebo † p value for interaction 0.97 Tsao M-S, et al. N Engl J Med 2005;353:133–

Progression-free survival HR=0.61, p<0.001* 25% 10% Survival distribution function Survival time (months) Tarceva Placebo Shepherd F, et al. N Engl J Med 2005;353:123–32 *HR and p (log-rank test) adjusted for stratification factors at randomisation and HER1/EGFR status

Efficacy of current treatment options in the second-line setting* *Survival cannot be compared directly because of different patient populations † n=156 (T) and 82 (BSC); ‡ n=253 1 Tarceva product information; 2 OSI and Roche data on file 3 Pemetrexed product information; 4 Docetaxel product information 5 Hanna N, et al. J Clin Oncol 2004;22:1589–97 Tarceva vs BSC 1,2 Docetaxel (75mg/m 2 ) vs pemetrexed 3 Docetaxel (75mg/m 2 ) vs BSC 4 T (n=488) BSC (n=243) D (n=288) P (n=283) D (n=55) BSC (n=100) PS (%) 0/ Prior regimens (%) 1  Median survival (months)* year survival (%) Median survival in PS 0/1 patients with one prior regimen 9.42 † 6.72 † ‡5 – –

Score Bezjak A, et al. J Clin Oncol 2005;23(Suppl. 16 Pt I):625s (Abs. 7018) BR.21: QoL impairments at baseline – mainly due to fatigue, cough, dyspnoea and pain GlobalRolePhysicalFatigueCoughDyspnoeaPain

BR.21: time to deterioration of QoL symptoms *Median † Adjusted log-rank Bezjak A, et al. J Clin Oncol 2005;23(Suppl. 16 Pt I):625s (Abs. 7018)

BR.21: change in symptoms *  10 point change from baseline at any time †  2 Bezjak A, et al. J Clin Oncol 2005;23(Suppl. 16 Pt I):625s (Abs. 7018)

BR.21: change in QoL domains (EORTC QLQ-C30) Improved* (%) Stable (%) Worse* (%) VariableTarceva Placebo Global QoL † Physical function † Role function Social function Emotional function † *  10 point change from baseline at any time (clinically significant) † p<0.01 Bezjak A, et al. J Clin Oncol 2005;23(Suppl. 16 Pt I):625s (Abs. 7018)

BR.21: adverse events (%) Tarceva (n=485)Placebo (n=242) AnyGrade 3, 4AnyGrade 3, 4 Rash Diarrhoea54 618<1 Nausea Vomiting Stomatitis17<1 3 0 Fatigue Ocular (all)27 1 9<1 Anorexia Infection

Tolerability of second-line therapies: haematological toxicities Shepherd F, et al. N Engl J Med 2005;353:123–32 Hanna N, et al. J Clin Oncol 2004;22:1589–97 Serious haematological toxicities may require hospitalisation and blood transfusions The most common non-haematological side effects were rash and diarrhoea (mainly mild to moderate)

Conclusions: Tarceva in NSCLC NSCLC has a high incidence and mortality Standard cytotoxic regimens offer clinical benefits, but are limited by substantial toxicities Tarceva is a new treatment option that has equivalent efficacy to approved chemotherapy options for second-line treatment, but is not associated with the side effects of chemotherapy Tarceva is a valuable new treatment option for patients with advanced NSCLC