Early Stage NSCLC: The Role of Chemotherapy Eric Vallieres, MD.

Slides:

Advertisements

Similar presentations

Advances and Emerging Therapy for Lung Cancer

Advertisements

Pulmonary Stereotactic Ablative Radiotherapy:

Highligths in management of gastrointestinal cancer April 11, 2008 CONTROVERSIES IN THE CONTROVERSIES IN THE ADJUVANT THERAPY ADJUVANT THERAPY OF GASTRIC.

Post-operative Radiotherapy for Esophageal Cancer Parag Sanghvi, M.D., M.S.P.H. Department of Radiation Medicine Esophageal Care Conference 3/26/2007.

DEBATE: What is the Optimal Sequence of Therapies for Stage II-III Adenocarcinoma of the Proximal Stomach? Michael A. Choti, MD Department of Surgery UT.

CHEMOTHERAPY AND BLADDER CANCER Walter Stadler, MD, FACP University of Chicago.

Rodney J. Landreneau, MD Professor of Surgery Heart, Lung & Esophageal Surgery Institute University of Pittsburgh Medical Center Management of Non-Small.

Controversies in Adjuvant Therapy for Pancreatic Cancer Parag Sanghvi M.D. Tasha McDonald M.D. Department of Radiation Medicine OHSU.

A Phase III Randomized, Double-Blind, Placebo-Controlled Trial of the Epidermal Growth Factor Receptor Inhibitor Gefitinb in Completely Resected Stage.

ANDREW NG PRINCE OF WALES HOSPITAL Role of primary chemoradiation in esophageal carcinoma.

U.S. Food and Drug Administration Notice: Archived Document The content in this document is provided on the FDA’s website for reference purposes only.

Giving Induction Radiation in Addition to Chemotherapy Is Not Associated with Improved Survival of NSCLC Patients with Operable Mediastinal Nodal Disease.

Controversies in the management of PSA-only recurrent disease Stephen J. Freedland, MD Associate Professor of Urology and Pathology Durham VA Medical Center.

The role of surgery in the management of mesothelioma Mr Martyn Carr Consultant Thoracic Surgeon Liverpool Heart and Chest Hospital.

Prof Ramesh S Bilimagga President AROI Group Medical Director - HCG.

AATS Postgraduate Course April 26, 2015 N2 - Current Evidence: Is There Role for Surgery? Is There a Role for Postop Radiation for Surprise N2? Linda W.

GCIG Meeting 29th May 2009 The Implications of Primary Chemotherapy for Clinical Trials Iain McNeish Professor of Gynaecological Oncology Barts and the.

SWISS TUMOR BOARD Lung Cancer March 26, 2009 Novotel Bern Prof. Dr. Mahmut Ozsahin Lausanne University Medical Center (CHUV), Lausanne.

LUNG CANCER: ASCO 2006 TOPICS Adjuvant therapy Clinical studies Meta-analysis ChemoXRT for stage III disease Advances in stage IV NSCLC New agents Predictive.

SURGERY FOR NSCLC GREG CHRISTODOULIDES MD, FACS, FCCP, FESTS

AATS/STS General Thoracic Surgery Symposium

1 Non–Small-Cell Lung Cancer Diagnosis and Staging EvaluationPurpose Physical examinationIdentify signs Chest x-rayDetermine position, size, number of.

The effect of surgeon volume on procedure selection in non-small cell lung cancer surgeries Dr. Christian Finley MD MPH FRCSC McMaster University.

Long-term follow-up of a prospective trial of pre-operative external-beam radiation and post-operative brachytherapy for retroperitoneal sarcoma LA Mikula,

Discussion abstracts Alberto Sobrero MD Ospedale San Martino Genoa, Italy.

Pancreatic Cancer Ali Shamseddine MD Proessor of Medicine AUBMC

What to do in stage III non small-cell lung cancer? Miklos Pless 28. November 2013.

Involved Field Radiotherapy versus No Further Treatment in Patients with Clinical Stages IA/IIA Hodgkin Lymphoma and a “Negative” PET Scan After 3 Cycles.

Delivering clinical research to make patients, and the NHS, better OG neoadjuvant therapy Brachytherapy Stephen Falk dd/mm/yyyy.

Dr Purvish M Parikh MD, DNB, FICP, PhD, ECMO, CPI, MBA 12 th July 2014, Kolkata 17th ICRO PG Teaching Course.

NSCLC stage IIIA type of chemotherapy ? Swiss tumor board Bern – Dr. Christian Monnerat Département Pluridisciplaire d’Oncologie – Hôpital Neuchâtelois.

Randomized Phase III Trial Comparing FOLFIRINOX (F: 5FU/Leucovorin [LV], Irinotecan [I], and Oxaliplatin [O]) versus Gemcitabine (G) as First-Line Treatment.

Taiwan 2000 Comparative evaluation in tolerance of neoadjuvant versus adjuvant docetaxel based chemotherapy in resectable gastric cancer in a randomized.

Effect of preoperative concurrent chemoradiotherapy on survival of patients with resectable esophageal or esophagogastric junction cancer: Results from.

Gemcitabine + Cisplatin +/- Bevacizumab as 1st-line Treatment of Advanced NSCLC: AVAiL Study Manegold PASCO 25:#7514, 2007/Ann.

Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma Marc de Perrot, Ronald Feld, Natasha B Leighl,

Phase III Study of Concurrent Chemotherapy and Radiotherapy (CT/RT) versus CT/RT followed by Surgical Resection for Stage IIIA(pN2) NSCLC Outcomes Update.

Adjuvant chemotherapy in Rectal Cancer?. What is the evidence for adjuvant chemotherapy? Do patients achieving a pathological complete response need chemotherapy?

OCEANS: A Randomized, Double- Blinded, Placebo-Controlled Phase III Trial of Chemotherapy with or without Bevacizumab (BEV) in Patients with Platinum-

Approaching early stage disease

Treatment Approaches for Stage IIIa(N2) Lung Cancer

Combined Modality Treatment of Locally Advanced Prostate Cancer: Radiation Therapy (RT) with Concurrent Androgen Deprivation Therapy (ADT) Howard Sandler.

The Role of Preoperative Approaches in Localized Gastro Esophageal Cancers David H. Ilson, MD, PhD Gastrointestinal Oncology Service Memorial Sloan-Kettering.

Neoadjuvant FOLFOX with Bevacizumab but without Pelvic Radiation for Locally Advanced Rectal Cancer Schrag D et al. Proc ASCO 2010;Abstract 3511.

Joan Schiller, MD Professor of Medicine Chief, Division of Hematology/Oncology University of Texas Southwestern Medical Center Deputy Director Simmons.

IL TRATTAMENTO INTEGRATO DELLO STADIO III Dr. Domenico Galetta Dip. Oncologia Medica Istituto Oncologico BARI Il Ruolo della Chemioterapia.

Adjuvant and Neoadjuvant Therapy in Non- Small Cell Lung Cancer Seminars in Oncology 2oo5;32 (suppl 2):S9-S15 Kyung Hee Medical Center Department of Thoracic.

Complete pathologic responses in the primary of rectal or colon cancer treated with FOLFOX without radiation A. Cercek, M. R. Weiser, K. A. Goodman, D.

Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer in the Elderly: A Population-Based Study in Ontario, Canada JOURNAL OF CLINICAL ONCOLOGY, VOLUME 30.

Adjuvant or neoadjuvant chemotherapy in minimal N2 stage IIIA nonsmall cell lung cancer Sofie De Craenea, Veerle Surmonta,b and Jan P. van Meerbeeck Current.

Neoadjuvant chemotherapy in the treatment of NSCLC Department of Thoracic Oncology, University Hospital Ghent, Belgium Current Opinion in Oncology 2007,

Emily Tanzler, MD Waseet Vance, MD

Short-term outcome of neo-adjuvant chemotherapy

Neoadjuvant & Adjuvant Chemotherapy for Hepatic Colorectal Metastases : When to use it ? SURGERY FIRST May 30 , 2009.

Perez EA et al. SABCS 2009;Abstract 80.

Treatment With Continuous, Hyperfractionated, Accelerated Radiotherapy (CHART) For Non-Small Cell Lung Cancer (NSCLC): The Weston Park Hospital Experience.

Management of Invasive Bladder Cancer

Adjuvant chemotherapy in NSCLC

Is there a role for adjuvant oxaliplatin in rectal cancer? - YES! -

Neoadjuvant therapy of rectal cancer – how can we make it better?

What is the most appropriate therapy for a 50 year old patient with T3N+ rectal cancer and isolated resectable liver metastases? Systemic chemotherapy->chemoradiation->surgery.

Christopher Crane, MD Professor, Dept of Radiation Oncology

What is the optimal pre-op therapy for esophagus and GE junction cancers?

Oesophageal and Gastric cancer: neo-adjuvant therapy

Adjuvant Radiation is Required for Gastric Cancer

Alan P. Venook, MD University of California, SF

Adjuvant Therapy in Gastric Cancer: Radiation Therapy Adds Nothing!

What’s new in stage III lung cancer?

Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer. A meta-analysis of two randomized trials E Mitry, A Fields,

Presentation transcript:

Early Stage NSCLC: The Role of Chemotherapy Eric Vallieres, MD

USA 2003

Clinical IB, IIA, IIB diseases Resection by lobectomy or more if cardiopulmonary reserves 5-y Survival = % Adjuvant Therapy ? Induction Therapy ? cT2N0 RUL NSCLC

Adjuvant Radiotherapy

N2 appeared to gain 1 month in survival...

MRC LCWP Stephens et al, Br J Cancer 1996

Adjuvant Radiotherapy No improvement in survival Improved loco-regional control with squamous histology (LCSG 773) but systemic failures lead to death...

Adjuvant Chemotherapy

Adjuvant Chemotherapy ALPI (Adjuvant Lung Project Italy) Tonato, PASCO 2002 abstract 1157

Overall Survival Events/Total CT 278/548 Control 288/540 HR=0.96 ( ) p=0.585 PROBABILITYPROBABILITY YEARS Median f/up of 63 months

Adjuvant Chemotherapy Over the last 30 years, on trial, the delivery of the intended chemotherapy has been consistently poor: LCSG 801 (CAP * 4) = 53% JCOG 8601 (C Vd *3) = 68% ALPI (MVdP * 3) = 70%

Clinical IB, IIA, IIB diseases Resection by lobectomy or more if cardiopulmonary reserves 5-y Survival = % Adjuvant Therapy = NO Induction Therapy ? cT2N0 RUL NSCLC Scan not available

3 cycles carboplatin/ paclitaxel re-imaged 4 weeks later PrePost Scans not available

The BLOT Phase II Study Induction Chemotherapy The BLOT Phase II Study Pisters K et al., J Thor CV Surg 2000; 119:

The BLOT Study 94 patients 98% completed induction chemo as planned Clinical major RR: 53/90 ( 58.9%) Pisters K et al., J Thor CV Surg 2000; 119;429

The BLOT Study Progression during induction: 3/98 ( 3%) Pisters K et al., J Thor CV Surg 2000; 119;429

The BLOT Study 86/94 were explored 77/ 94 had a R0 resection ( 82%) One postoperative death Operative morbidity comparable to historical series of Surgery alone Pisters K et al., J Thor CV Surg 2000; 119;429

The BLOT Study Induction carboplatin/ paclitaxel chemotherapy is safe and feasible prior to resection of clinical early NSCLC Pisters K et al., J Thor CV Surg 2000; 119:

Induction Chemotherapy The Depierre Phase III Study Depierre et al., Proc ASCO 1999, abstract 1792 Adjuvant RT for pT3 and pN2

OP MIP>OP Median survival (months) 26 p= y (%) 73 NS 2y (%) 52 NS 3y (%) 41 NS 49 Operative mortality 4.5% NS 7.8% The Depierre Study Depierre et al., J Clin Oncol 2001; 20:

Overall Survival 1253 Years Years p = 0.15 PCTPRS ||||| _ _ _ _ _ _ _ _ _ _ 6 | Reference date : Nov 1, 2000 PCT arm PRS arm Patients at risk

Vanderbilt Historical comparison Induction PC Surgery alone N Stages 2.52 < age, PFT, comorbid. = Life Threat. Comp. (%) 27% % Reintubation 17.6% % Tracheostomy 12% Mortality 5.6% Induction chemotherapy Perioperative complications ? Roberts et al., Ann Thorac Surg 2001; 72: 885-8

The Depierre Study 30 day operative mortality MIP> S n= % S n= % NS Breton JP et al., Proc ASCO 2001, abstract 1239

The Depierre Study 30 day operative morbidity MIP> S 39 in 33 pts S 27 in 25 pts NS Breton JP et al., Proc ASCO 2001, abstract 1239

The Depierre Study BPF/ empyemas MIP> S 10* ( 8 early + 2 late) S 5 NS * 8/10 in N2 pts, 9/10 after pneumonectomy Breton JP et al., Proc ASCO 2001, abstract 1239

The Depierre Study Pulmonary infections MIP> S 10 S 11 NS Breton JP et al., Proc ASCO 2001, abstract 1239

Does induction chemotherapy (without radiation) really increase the morbidity and mortality of lung resection ?

Randomized Data Stage III Experience

RESECTABLE N2 DISEASE Pre chemotherapy Post chemotherapy Scans not available

The Roth Phase III Study (MDACC) Induction Chemotherapy The Roth Phase III Study (MDACC) Roth J NCI May 1994

The Rosell Phase III Study Induction Chemotherapy The Rosell Phase III Study Rosell NEJM Jan 1994 Adjuvant mediastinal RTx 50 Gy

Operative risks after induction chemotherapy Phase III data OPERATIVE MORTALITY Pass 1992 CS(EP)>S> RT (n=13) 0% S>RT (n=14) 0% Rosell 1994 CS(MIP)>S > RT (n=30) 2/ % S > RT (n=30) 2/ % [all 4 deaths (2+2) were respiratory] Roth 1994 CS(CyEP)>S (n=28) 0* S alone (n=32) 6 * had 3 treatment related deaths Pass, Ann Thor Surg 1992; Rosell, NEJM 1994; Roth, J NCI 1994

Retrospective Data

Operative risks after induction chemotherapy MDACC Aug 1996 to Apr consecutive “lobectomies or more” for NSCLC 76 after induction chemotherapy 259 surgery alone Prospective data collection of peri-operative events Siegenthaler et al., Ann Thor Surg 71:1105, 2001

Operative risks after induction chemotherapy MDACC (-ed) Induction chemotherapy: carboplatin/ paclitaxel in 93% of pts Siegenthaler et al., Ann Thor Surg 71:1105, 2001

Operative risks after induction chemotherapy Siegenthaler et al., Ann Thor Surg 71:1105, 2001

Operative risks after induction chemotherapy MDACC (-ed) Stage specific analysis : no difference in morbidity of CS vs. S alone Multivariate analysis: only CAD and pneumonectomy were independent risk factors for a major postoperative event. Siegenthaler et al., Ann Thor Surg 71:1105, 2001

Operative risks after induction chemotherapy MSKCC Jan 1993 to Dec pulmonary resections after induction therapy ( ages ranged 25-82) Preop chemotherapy: carboplatin/ paclitaxel 32% MVP 38% Preop radiotherapy as well : 18% Martin J et al., Ann Thorac Surg 2001; 72:

Operative risks after induction chemotherapy MSKCC (-ed) 297 lobectomies ( 9 sleeves, 26 bilobectomies ) 97 pneumonectomies ( 20%) 18 lesser resections, 58 O&C 22% were extended resections Martin J et al., Ann Thorac Surg 2001; 72:

Operative risks after induction chemotherapy MSKCC (-ed) Operative mortality Overall 3.8% Lobectomy 2.4% Left Pneumonectomy 0% Right Pneumonectomy 23.9% Multivariate analysis: right pneumonectomy was the only predictor of mortality Martin J et al., Ann Thorac Surg 2001; 72:

Operative risks after induction chemotherapy MSKCC (conclusion) Major morbidity 26.6%, mainly respiratory Multivariate analysis: Increased operative blood loss, low FEV1 and right pneumonectomy were the only independent predictors of postoperative morbidity The type of induction regimen was not a risk factor. Martin J et al., Ann Thorac Surg 2001; 72:

Operative risks after induction chemotherapy Does induction chemotherapy without radiationtherapy really increase the morbidity and mortality of lung resection ? Probably not… but most of the data published so far is either retrospective and/or comparing to historical controls...

Induction Therapy ( pre-operative ) Ongoing Studies

Early Stage Disease Phase III Trial INT S 9900 cT2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction carboplatin/ paclitaxel 3 cycles Resection Activated Accrual goal = 600 1/24/03 = 279

Phase III Trial INT S 9900 “Son of BLOT” “ BLOT or KNOT” Through SWOG, NCCTG, ECOG, RTOG, ACOSOG, NCIC and the CTSU.

Early Stage Disease NATCH* ( Neoadjuvant/ Adjuvant Taxol Carboplatin Hope) *Switzerland, Spain, Germany, Portugal, Sweden Activated 4.00 Accrual goal = 624

Early Stage Disease ChEST (Chemotherapy for Early Stage Tumor) cT2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction gemcitabine/ cddp 3 cycles Resection Italy Accrual goal =

Early Stage Disease MRC Lu-22 cT1N0, T2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction chemotherapy* 3 cycles, Q 3weeks Resection UK + EORTC ( 6/02) Activated Jan 1998 Accrual goal = 450 April 2002 = 239 *MVP, MIP, Cis-Vinorelbine, Cis-Gem

Will induction chemotherapy become the standard of care for our patients with early stage disease ? Only by completing the ongoing clinical trials in a timely fashion, will we be able to answer this very important question.