CHORUS: trial | Bending the Curve: Trial by Trial

CHORUS

Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial

Phase 3N = 552NCT00075712

Population

Women with suspected stage III or IV ovarian cancer (552 randomly assigned, 550 eligible)

Design

Open-label, randomised, non-inferiority trial in 87 hospitals in the UK and New Zealand. Women with suspected stage III or IV ovarian cancer were assigned 1:1 to primary surgery followed by six cycles of chemotherapy, or three cycles of primary chemotherapy, then surgery, then three more cycles. Chemotherapy was carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m2, an alternative carboplatin combination, or carboplatin alone. To establish non-inferiority the upper bound of a one-sided 90% CI for the hazard ratio had to be below 1.18. Registered as ISRCTN74802813; the ISRCTN record lists ClinicalTrials.gov NCT00075712 (organisation ID RCOG-MRC-CHORUS), which describes a feasibility design with an estimated 150 participants.

Primary endpoint

Arms

Primary surgery (control, n = 276): Primary surgery followed by six cycles of chemotherapy
Primary chemotherapy (experimental, n = 274): Three cycles of primary chemotherapy, then surgery, then three more cycles of chemotherapy

People

Kehoe S

OSHR 0.87 (95% CI 0.72–1.05)Δ median OS+1.5 monthsΔ Grade 3 or 4 postoperative adverse events−10 points

Show the numbers

Results reported for CHORUS
Endpoint	Analysis	Primary chemotherapy	Primary surgery	Effect
OSIntention-to-treat population (550 eligible women)	primaryKehoe 2015	median 24.1 months	median 22.6 months	HR 0.87 (95% CI 0.72–1.05)Hazard ratio for death favouring primary chemotherapy; the upper bound of the one-sided 90% CI was 0.98 against the pre-specified non-inferiority limit of 1.18. 451 deaths: 231 with primary surgery and 220 with primary chemotherapy.
Grade 3 or 4 postoperative adverse eventsWomen with postoperative data (252 primary surgery, 209 primary chemotherapy)	primaryKehoe 2015	14%	24%	P=0.000760 of 252 women versus 30 of 209. Deaths within 28 days after surgery: 14 women (6%) with primary surgery versus 1 woman (<1%) with primary chemotherapy (p=0.001).

Results reported for CHORUS
Endpoint	Analysis	Primary chemotherapy	Primary surgery	Effect
OSIntention-to-treat population (550 eligible women)	primaryKehoe 2015	median 24.1 months	median 22.6 months	HR 0.87 (95% CI 0.72–1.05)Hazard ratio for death favouring primary chemotherapy; the upper bound of the one-sided 90% CI was 0.98 against the pre-specified non-inferiority limit of 1.18. 451 deaths: 231 with primary surgery and 220 with primary chemotherapy.
Grade 3 or 4 postoperative adverse eventsWomen with postoperative data (252 primary surgery, 209 primary chemotherapy)	primaryKehoe 2015	14%	24%	P=0.000760 of 252 women versus 30 of 209. Deaths within 28 days after surgery: 14 women (6%) with primary surgery versus 1 woman (<1%) with primary chemotherapy (p=0.001).

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.87	0.72–1.05

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Primary surgery (control)
Primary chemotherapy (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Primary surgery	Primary chemotherapy
0	100.0%	100.0%
15	63.1%	65.0%
30	39.8%	42.2%
45	25.2%	27.4%
60	15.9%	17.8%

Appears in

2010 Neoadjuvant chemotherapy vs primary surgery: EORTC 55971, CHORUS

Sources

Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015;386(9990):249-57.
PubMed DOI