Authors: Lee S-M et al. Reviewers: Dr. C. Butts, Dr. R. Burkes Date posted: Sept 20, 2007

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A phase III, randomized, double-blind, placebo controlled trial of etoposide/carboplatin with or without

thalidomide in advanced small cell lung cancer

Authors: Lee S-M et al.

Reviewers: Dr. C. Butts, Dr. R. Burkes

Date posted: Sept 20, 2007


Background

• Small cell lung cancer is highly angiogenic.

• Previous phase II trial of thalidomide with chemotherapy was well tolerated.

• Randomized phase II trial (Pujol et al) of chemo +/- thalidomide in responders to initial chemotherapy suggested a survival advantage of 3 months.


Study Design

• Randomized phase III, placebo controlled.• End points were OS, TTP, RR, toxicity and

QoL.• Powered to show 7% improvement in 2

year survival (12%-19%).• Placebo or thalidomide to start with chemo

and could continue for 2 years.• Starting dose of 100 mg, escalate to 150

mg at 1 month and 200 mg at 2 months.


Patients

• Limited or extensive small cell

• PS 0-3

• Chemo-naive

• Thoracic and PCI offered to Limited stage patients having response to chemotherapy.


R

Treatment A: Carboplatin (AUC 5 or 6) and etoposide 100 mg/m2 Day 1 & 2 q 3 weeks, max 6 plus thaliomide daily

Treatment B: same chemo plus placebo daily

Limited/extensive,PS 0-3,

Chemo-naive


RESULTS

Treatment

Thalidomide

Treatment

Bp-value

Response Rate (%)

NR NR

2 year survival (%)

13% 13% NS

OS

(median, mos)

10.2 10.5 NS


STUDY COMMENTARY

•Significantly more thrombotic events in thalidomide arm (18% vs 11%).

•49% of patients were extensive stage. 1 year survival in ED patients ws lower in thalidomide arm (25% vs 75%)

•No particular subgroup seemed to benefit.

•Possible reasons for the differences between this trial and Pujol study:

•Included both LD and ED

•Lack of selection for responders

•Lower dose of thalidomide in this study (100 mg versus 400 mg)

•Should be noted that the published results of the Pujol trial (JCO Sept 2007) show no significant survival advantage.


BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

•This trial is another in the long list of disappointing small cell trials.

•These results combined with the negative result seen in the final publication of the Pujol trial may result in reconsidering further trials with newer generation thalidomide derivatives.

Authors: Lee S-M et al. Reviewers: Dr. C. Butts, Dr. R. Burkes Date posted: Sept 20, 2007

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Transcript of Authors: Lee S-M et al. Reviewers: Dr. C. Butts, Dr. R. Burkes Date posted: Sept 20, 2007