Early Treatment of Relapsed Ovarian Cancer Based on CA125 Level Alone Versus Delayed Treatment Based on Conventional Clinical Indicators

Results of the Randomized MRCOV05 and EORTC 55955 Trials

Rustin G et al.ASCO 2009; Abstract 1. (Plenary Oral Presentation)

Source: Rustin G et al. ASCO 2009; Abstract 1.

Introduction

80% of patients with advanced ovarian cancer (OC) will relapse after first line chemotherapy

Most of these patients will benefit from further therapy

Serial measurements of circulating tumor markers (CA125) have the potential for earlier detection of relapse

It is unclear whether patients benefit from earlier treatment of chemical relapse

Current study objectives:

– Investigate the benefit of early chemotherapy for relapsed OC, based on raised CA125 level alone, versus delayed chemotherapy based on conventional clinical indicators

CA125 >2x upper limit of normal (ULN)

RANDOMIZED

N = 529 (37%)

Trial Design

Ovarian cancer in complete remission after first-line platinum based chemotherapy and a normal

CA125

REGISTER: Blinded CA125 measured every 3 months

N = 1,442

Early treatment (Clinician and patient informed)

N=265N=254 (96%) started second-line chemo

Delayed treatment (Clinician not informed, treatment delayed until clinically indicated)

N=264N=233 (88%) started second-line chemo

Source: Rustin G et al. ASCO 2009; Abstract 1.

Clinical relapse/DeathCA125 <2x ULNConsent withdrawal/Other

Primary Outcome:Overall Survival

Source: With permission from Rustin G. ASCO 2009; Abstract 1.

No difference in overall survival between early

and delayed second-line chemotherapy

0

0.00

0.25

0.50Proportion

surviving

Months since randomisation

EarlyDelayed

Abs diff at 2 years = 0.1%(95% CI diff = -6.8, 6.3%)

Numbers at risk

265 247 211 165 131 94 72 51 38 31 22264 238 203 187 129 103 69 53 38 31 19

HR = 1.00 (95% CI 0.82-1.22) p = 0.98

0.75

1.00

6 12 18 24 30 36 42 48 54 60

EarlyDelayed

Secondary Outcome:Time from Randomization to Second- or Third-line Treatment (or Death)

Source: Rustin G et al. ASCO 2009; Abstract 1.

Outcome Measure

Early(N=265)Months

Delayed(N=264)Months

Hazard ratio

(95% CI) P value

Time from randomization to second-line chemotherapy

0.8 5.6 0.29(0.24-0.35)

<0.00001

Time from randomization to third-line chemotherapy or death

12.5 17.1 0.69(0.58-0.83)

0.0001

Quality of Life (QoL)

Source: Rustin G et al. ASCO 2009; Abstract 1.

Outcome Measure

Early(N=190)Months

Delayed(N=194)Months

Hazard ratio

(95% CI) P value

Time from randomization to first deterioration of GHS or death

3.1 5.8 0.71(0.57-0.87)

0.001

Overall time spent with “good” GHS

7.1 9.2 NA 0.15

EORTC QLQ-C30 questionnaire Q 3 months from registration and prior to each cycle of chemo, until the end of third-line treatment

“Good” Global Health Score (GHS): improved or <10% from pre-randomization score

Global Health deterioration: >10% from pre-randomization score

Summary and Conclusions

In patients receiving early treatment based on rise in CA125

– Second-line chemo commenced a median of 4.8 months earlier

– Third-line chemo commenced a median of 4.6 months earlier

This early treatment did not improve overall survival

– Hazard Ratio: 1.00, p=0.98

Early treatment with chemotherapy does not improve QoL

There appears to be no benefit from early detection of relapse by routine CA125 measurements

Source: Rustin G et al. ASCO 2009; Abstract 1.

Practice Implications

Recommend less frequent monitoring of CA125 values in asymptomatic patients

Consider delaying palliative chemotherapy until clinical recurrence (even in the presence of rising CA125)

Women can be offered informed choices in follow-up:

– No routine CA125 measurement, but rapid access to CA125 testing if symptoms or signs of relapse

– Regular CA125 measurementsSource: Rustin G et al. ASCO 2009; Abstract 1; Karlan B. ASCO 2009; Discussion