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OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in

patients with metastatic colorectal cancer (MRC).

A GERCOR study.

Reviewer: Dr Scott BerryDate posted: June 21, 2007

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Rationale

• The OPTIMOX1 trial randomized patients with metastatic colon cancer who had received 3 months of FOLFOX induction therapy to – continued FOLFOX – vs q 2 weekly infusional 5FULV maintenance with

re-introduction of FOLFOX when tumours had progressed beyond their baseline size

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Rationale• The OPTIMOX 1 trial demonstrated that the FULV

maintenance strategy generally reduced toxicities but did not reduce survival (Tournigand JCO 2006)

• OPTIMOX 2 was designed to see whether the 5FULV maintenance could be omitted in favour of a “chemotherapy free interval” after FOLFOX induction

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Rationale• The OPTIMOX 1 trial introduced the concept

of Duration of Disease Control:

J Clin Oncol 24:394-400, 2006 by American Society of Clinical Oncology

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ROPTIMOX 1:

mFOLFOX7 x 6 cy 5FULV maintenance until progression

Then FOLFOX7 reintroduction

OPTIMOX 2:mFOLFOX7 x 6 cy

No maintenance until progressionThen FOLFOX7 reintroduction

Untreated Metastatic

Colon Cancer

N=200

Primary Outcome: OS

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RESULTS

Optimox 1 Optimox 2 p-value

Chemo FreeInterval (median, weeks)

N/A 17

DDC(median, weeks)

52 39 P=0.39

OS (median,

mos)26 19 P=0.0549

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STUDY COMMENTARY

• The OPTIMOX2 strategy of 3 month induction chemo followed by a chemo free interval results in a clinically significant (borderline statistical significance) detriment in overall survival

• Why?

• ? Longer induction

• ? Shorter break before re-introduction

• Labianca - ASCO 2006

• Intermittent FOLFIRI 2 mos on / 2 mos off vs Continuous FOLFIRI demonstrated equivalent survival

• ? Different maintenance strategy

• DREAM (OPTIMOX3) - Bevacizumab/Erlotonib vs Bevacizumab maintenance after FOLFOX+Bev induction

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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• The current variable availability of oxaliplatin as first line therapy for metastatic colon cancer likely limits the use of an “OPTIMOX” strategy

• For Canadian oncologists contemplating an induction maintenance strategy after 3 months of FOLFOX chemotherapy, the 5FULV component of therapy should be continued as maintenance therapy after induction

• Other intermittent chemotherapy strategies such as that reported by Labianca at ASCO 2006 have decreased exposure to chemo without a detriment in survival