Highlights
- •Survival noninferiority of NACT compared to PDS was not confirmed in this study.
- •Noninferiority of the previous studies cannot be denied because of smaller numbers.
- •There seems to be diversity in the efficacy of PDS/NACT among subgroups of patients.
Abstract
Background
Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy
(NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS
studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness
of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall
survival (OS).
Methods
Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e.
TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary
endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with
PDS was 1·161. The planned sample size was 300.
Findings
Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The
median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8%
confidence interval (CI) 0·835–1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS
and NACT (HR: 0·96 [95%CI 0·75–1·23]). In the PDS arm, 147/149 underwent PDS and 49/147
underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved
in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130)
of IDS in the NACT arm. Optimal surgery (residual tumour <1 cm) was achieved in 37%
(55/147), 63% (92/147), and 82% (107/130 respectively. In the NACT, PS 2/3, serum
albumin ≤2·5, CA125 > 2000 an institution with low study activity was advantageous,
whereas clear/mucinous histology was disadvantageous for OS.
Interpretation
The noninferiority of NACT was not confirmed. NACT may not always be a substitute
for PDS. However, as our study had smaller numbers, the noninferiority of the previous
studies cannot be denied.
Funding
Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan.
Clinical trial information
UMIN000000523.
Keywords
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Article info
Publication history
Published online: March 13, 2020
Accepted:
February 9,
2020
Received in revised form:
February 5,
2020
Received:
August 2,
2019
Identification
Copyright
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