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. 2024 Feb;130(3):425-433.
doi: 10.1038/s41416-023-02528-z. Epub 2023 Dec 14.

Discordance between GCIG CA-125 progression and RECIST progression in the CALYPSO trial of patients with platinum-sensitive recurrent ovarian cancer

Danka Sinikovic Zebic  1   2 , Angelina Tjokrowidjaja  3   4 , Katherine Elizabeth Francis  3   5 , Michael Friedlander  6 , Val Gebski  3 , Alain Lortholary  7 , Florence Joly  8 , Annette Hasenburg  9 , Mansoor Mirza  10 , Ursula Denison  11 , Sabrina Chiara Cecere  12 , Annamaria Ferrero  13 , Eric Pujade-Lauraine  14 , Chee Khoon Lee  3   4
Affiliations

Discordance between GCIG CA-125 progression and RECIST progression in the CALYPSO trial of patients with platinum-sensitive recurrent ovarian cancer

Danka Sinikovic Zebic et al. Br J Cancer. 2024 Feb.

Abstract

Background: CA-125 alone is widely used to diagnose progressive disease (PD) in platinum-sensitive recurrent ovarian cancer (PSROC) on chemotherapy. However, there are increasing concerns regarding its accuracy. We assessed concordance between progression defined by CA-125 and RECIST using data from the CALYPSO trial.

Methods: We computed concordance rates for PD by CA-125 and RECIST to determine the positive (PPV) and negative predictive values (NPV).

Results: Of 769 (79%) evaluable participants, 387 had CA-125 PD, where only 276 had concordant RECIST PD (PPV 71%, 95% CI 67-76%). For 382 without CA-125 PD, 255 had RECIST PD but 127 did not (NPV 33%, 95% CI 29-38). There were significant differences in NPV according to baseline CA-125 (≤100 vs >100: 42% vs 25%, P < 0.001); non-measurable vs measurable disease (51% vs 26%, P < 0.001); and platinum-free-interval (>12 vs 6-12 months: 41% vs 14%, P < 0.001). We observed falling CA-125 levels in 78% of patients with RECIST PD and CA-125 non-PD.

Conclusion: Approximately 2 in 3 women with PSROC have RECIST PD but not CA-125 PD by GCIG criteria. Monitoring CA-125 levels alone is not reliable for detecting PD. Further research is required to investigate the survival impact of local therapy in radiological detected early asymptomatic PD.

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Conflict of interest statement

D. S. Zebic reports honoraria from Merck. A. Tjokrowidjaja reports research funding (institution) from AZ, support for attending meetings from GSK. K. E. Francis reports funding from BMS, support for attending educational meeting. M. Friedlander reports consulting fees from Novartis, AstraZeneca, MSD, GSK; honoraria from AstraZeneca, GSK, MSD; grants (institution) from AstraZeneca, Novartis, Beigene; participation on a Data Safety Monitoring Board or Advisory Board for AGITG. V. Gebski reports no conflict of interest. A. Lortholary reports participation on Advisory Board for AstraZeneca, MSD Tesaro; honoraria from Clovis Oncology, Roche; congress participation for Novartis, Pfizer, MAD, Lilly, Roche; member of CS3 sein UNICANCER. F. Joly reports participation on Advisory Board for GSK, AstraZeneca, Clovic, Seagen, Janssen, ESAI, Bayer, Viatris, MSD, Ipsen, Amgen, Astellas; honoraria from GSK, Bayer, ESAI, MSD; research funding (personal) from AstraZeneca, GSK; participation member for ASCO, GCIG; congress travel fees from GSK, MSD, ESAI, Ipsen. A. Hasenburg reports honoraria from AstraZeneca, Celgen, GSK, LEO Pharma, MedConcept GmbH, Med update GmbH, Medicultus, Pfizer, Promedicis GmbH, Softconsult, Roche Pharma AG, Streamedup GmbH, Tesaro Bio Germany GmbH; participation on Advisory Board for AstraZeneca, GSK, LEO Pharma, PharmaMar, Promedicis GmbH, Roche Pharma AG, Tesaro Bio Germany GmbH, MSD Sharp&Dohme GmbH. M. Mirza reports participation Data Safety Monitoring Board or Advisory Board for Astra Zeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab; honoraria from Astra Zeneca, GSK; research funding (institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of Board of Directors). U. Denison reports no conflict of interest. S. C. Cecere reports honoraria from AstraZeneca, MSD, Pharmamar. A. Ferrero reports honoraria from AstraZeneca, MSD, GlaxoSmithKline, Clovis; participation Data Safety Monitoring Board or Advisory Board for AstraZeneca, MSD. E. Pujade-Lauraine reports honoraria (personal) from AstraZeneca, GSK, Agenus; grants (institution) from AstraZeneca, Merck; participation on Advisory Board or Data Safety Monitoring Board for Incyte, Roche, Pfizer; and is an employee of ARCAGY GINECO research. C.K. Lee reports honoraria from AstraZeneca, Roche, Amgen, GSK, Merck KGA, Novartis, Pfizer, Janssen; grants (institution) from AstraZeneca, Roche, Amgen, Merck KGA; support for attending meetings from AstraZeneca.

Figures

Fig. 1
Fig. 1. Study population flow chart.
*Secondary analysis includes n = 804 patients with CA125 PD up to 4 weeks after RECIST PD.
Fig. 2
Fig. 2
Kaplan–Meier Curve for progression free survival (PFS) in (a) CPLD (carboplatin/pegylated liposomal doxorubicin) and (b) CP (carboplatin/paclitaxel) arms. PFS progression free survival, CPLD carboplatin/pegylated liposomal doxorubicin, CP carboplatin/paclitaxel; CA-125 PD, CA-125 progression; RECIST PD, RECIST progression. y-axis – proportion alive, x-axis – progression time in months.
Fig. 3
Fig. 3
Forest plot showing (a) positive predictive values (PPV) and (b) negative predictive values (NPV) for primary analyses in patient subgroups. Concordance percentage for each subgroup variable, expressed as positive predictive value (a) and negative predictive value (b), is represented by the small diamond, and the horizontal line crossing the square represents the 95% confidence interval (CI). The large diamond represents the pooled overall measure of concordance. PPV positive predictive value (probability of patients with CA-125 PD that also had RECIST PD), NPV negative predictive value (probability that those without CA125 PD also did not have RECIST PD).
Fig. 4
Fig. 4
Scatter plots and median (IQR) for discordant groups: (a) Patients (N = 255) with RECIST PD only but CA-125 not meeting GCIG criteria for PD with (i) rising CA-125, (ii) stable CA-125, (iii) falling CA-125 values. b Patients (N = 111) with GCIG CA-125 PD only but without RECIST PD (iv) rising CA-125, (v) stable CA-125, (vi) falling CA-125 values. Dots represent the median CA-125 value at the particular time-point with bars representing the associated interquartile range. Patterns of CA-125 defined as: Rising CA-125 (>50% baseline at time of RECIST PD); Stable CA-125 (>15% below and ≤50% above baseline); Falling CA-125 (≤15% below baseline).
See this image and copyright information in PMC

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