reviewer: dr. randeep sangha date posted: june 21, 2007

www.OncologyEducation.ca

Phase III trial of cisplatin (P) plus etoposide (E) plus concurrent Phase III trial of cisplatin (P) plus etoposide (E) plus concurrent chest radiation (XRT) with or without consolidation docetaxel chest radiation (XRT) with or without consolidation docetaxel

(D) in patients with inoperable stage III non-small cell lung (D) in patients with inoperable stage III non-small cell lung cancer (NSCLC): HOG LUN 01-24/USO-023cancer (NSCLC): HOG LUN 01-24/USO-023

Authors: Hanna et al. Abstract # 7512

Reviewer: Dr. Randeep Sangha

Date posted: June 21, 2007


Background

• Stage III inoperable NSCLC

• SWOG 9019– Phase II study enrolling 50 Stage IIIB pts– Platinum (P)/Etoposide (E) + XRT → consolidation EP x 2– 5 yr overall survival (OS) of 15% and median survival time

(MST) of 15 months

Albain et. al. JCO 2002, 20:3454-60

Less effective More effective


Background

• SWOG 9504

– Phase II single arm study

– Consolidation Docetaxel (D) following PE/XRT further improved survival

– MST 26 months

Gandara et. al., JCO 2003;21:2004-10


Study DesignStudy Question

– In a randomized, prospective, Phase III study comparing EP/XRT with or without consolidation D for Stage III NSCLC patients, will D offer a significant survival advantage?

Endpoints– Primary Endpoint

• Overall survival (OS)

– Secondary Endpoints• Progression free survival (PFS)• Toxicity

Study Population– Data Safety Monitoring Board recommended early termination

after analysis of 203 patients (147 randomized)• Based upon evidence of futility (predefined as p>0.7271)


Study Design

• Inoperable Stage IIIA/B NSCLC• PS 0-2• FEV1 ≥ 1• <5% weight loss

• P 50 mg/m2 d1,8,29,36• E 50 mg/m2 d1-5, 29-33• XRT to 59.4 Gy R

D 75 mg/m2 q21d x 3 cycles

Observation


Results

Docetaxel Observation p-value

PFS (months) 12.3 12.9 0.9412

OS* (months)21.5

(OS3yrs 27.2%)24.1

(OS3yrs 27.6%) 0.9402

*OS for all pts: 21.1 months


Study Commentary

• Docetaxel consolidation does not improve survival when compared with observation following PE/XRT

• Increased toxicities with Docetaxel consolidation– Higher rate of hospitalization– Increased grade 3/4 toxicities– Increased treatment related death

• PE/XRT should be the reference regimen for stage III inoperable NSCLC


Bottom Line for Canadian Medical Oncologists

Previous studies show that concurrent chemoradiation is more effective than sequential chemoradiation or radiation alone for Stage III inoperable NSCLC

Three cycle of consolidation Docetaxel after concurrent chemoradiation does not significantly add to survival Associated with significant Grade 3/4 toxicities and an

increased hospitalization rate

There is a lack of Phase III evidence demonstrating a survival benefit for consolidative therapies in Stage III NSCLC

Concurrent chemoradiation alone could be considered standard treatment for Stage III inoperable NSCLC

reviewer: dr. randeep sangha date posted: june 21, 2007

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