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Clinical Trial
. 2024 May;629(8014):1142-1148.
doi: 10.1038/s41586-024-07384-2. Epub 2024 Apr 8.

The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer

Jean E Abraham  1   2 , Karen Pinilla  3   4 , Alimu Dayimu  5 , Louise Grybowicz  6 , Nikolaos Demiris  7 , Caron Harvey  6 , Lynsey M Drewett  8 , Rebecca Lucey  3   4 , Alexander Fulton  3   4 , Anne N Roberts  6 , Joanna R Worley  3   4 , Anita Chhabra  9 , Wendi Qian  10 , Anne-Laure Vallier  6 , Richard M Hardy  6 , Steve Chan  11 , Tamas Hickish  12 , Devashish Tripathi  13   14 , Ramachandran Venkitaraman  15 , Mojca Persic  16 , Shahzeena Aslam  17 , Daniel Glassman  18 , Sanjay Raj  19   20   21 , Annabel Borley  22 , Jeremy P Braybrooke  23 , Stephanie Sutherland  24 , Emma Staples  25 , Lucy C Scott  26 , Mark Davies  27 , Cheryl A Palmer  28 , Margaret Moody  29 , Mark J Churn  30   31   32 , Jacqueline C Newby  33 , Mukesh B Mukesh  34 , Amitabha Chakrabarti  35 , Rebecca R Roylance  36 , Philip C Schouten  37 , Nicola C Levitt  38 , Karen McAdam  39 , Anne C Armstrong  40 , Ellen R Copson  41 , Emma McMurtry  42 , Marc Tischkowitz  43 , Elena Provenzano  37 , Helena M Earl  3   4
Affiliations
Clinical Trial

The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer

Jean E Abraham et al. Nature. 2024 May.

Abstract

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .

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Conflict of interest statement

The authors declare competing financial interests in the form of research grants and honoraria for lectures. The funders of the research grants and honoraria had no role in the study design, data collection, analysis, interpretation or writing of the manuscript. J.E.A. reports honoraria, conference attendance travel support and a grant from AstraZeneca; and honoraria from Esai and Pfizer for lectures. M.M. reports shares in AstraZeneca. M.B.M. reports advisory board membership of Roche, Pfizer, MSD, Daiichi Sankyo, Gilead, AstraZeneca, Novartis, the Menarini Group, Genomic Health (Precision Medicine) and Seagen; speaker honoraria from Roche, BMS, Seagen, Pfizer, Daiichi Sankyo, AstraZeneca, Lilly, MSD, Genomic Health (Precision Medicine), Eisai and Novartis; and meeting expenses from Roche, Eli Lilly, Novartis and MSD. R.R.R. reports honoraria from Daiichi Sankyo, AstraZeneca, Novartis and Pfizer; membership of advisory boards for Daiichi Sankyo, Eli Lilly, Pfizer and AstraZeneca; and travel and conference attendance from BMS, Pfizer and Roche. P.C.S. reports that their partner is employed by AstraZeneca. N.C.L. reports shares in AstraZeneca. A.C.A. reports research funding paid to their institution from AstraZeneca; conference fees and travel expenses from Roche and Novartis; conference fees from MSD; membership of Roche and AstraZeneca advisory boards; and a grant for an educational project from Gilead. E.R.C. reports honoraria from AstraZeneca, Eli Lilly, Novartis, Pfizer and Roche; membership of advisory boards for AstraZeneca, Eli Lilly, Pfizer, Menarini Stemline UK and Novartis; consultancy for Pfizer; conference fees, travel and accommodation from Roche and Novartis; an educational grant from Daiichi Sankyo; and research funding and support from SECA and AstraZeneca. E.P. reports honoraria from Roche, Novartis and AstraZeneca. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Trial CONSORT diagram.
*The first main reason for treatment discontinuation was reported.
Fig. 2
Fig. 2. pCR rate by treatment arm and TIL group.
a,b, pCR rate by treatment arm (a) and TIL group (≥60% versus <60%) (b). Data were analysed from a total of 276 patients in the research (gap schedule) and 267 control arms. Error bars, 95% CI of the proportion based on exact method. The statistical test was based on the two-tailed chi-squared test.
Fig. 3
Fig. 3. Kaplan–Meier curves of key survival end points.
a–c, EFS (a), OS (b) and DDFS (c) in patients in the modified intention-to-treat group by treatment arm.
Fig. 4
Fig. 4. Kaplan–Meier curves of survival by pathological response and treatment arm.
a,b, EFS by pathological response (a) and by pathological response and treatment arm (b). c,d, OS by pathological response (c) and by pathological response and treatment arm (d) in patients in the modified intention-to-treat group.
Extended Data Fig. 1
Extended Data Fig. 1. Trial Flow Chart: PARTNER Trial for the TNBC Cohort.
Trial Flow Chart: PARTNER Trial for the TNBC Cohort.
Extended Data Fig. 2
Extended Data Fig. 2. Forest plot of the primary end-point in subgroups.
The data are the numbers and proportions of patients with pathological complete response (pCR). Data were analysed from a total of 276 in research (gap schedule) and 267 control arms. Estimates are the difference in the pCR and 95% CI based on the score method between research arm and control arm.
Extended Data Fig. 3
Extended Data Fig. 3. Additional Kaplan-Meier curves of survival endpoints (part 1).
Relapse free survival (A), local recurrence free survival (B), time-to-second cancer (C) and breast cancer specific survival (D) by treatment arm (control and research arm).
Extended Data Fig. 4
Extended Data Fig. 4. Additional Kaplan-Meier curves of survival endpoints (part 2).
Relapse free survival (A), overall survival (B), and distant disease-free survival (C) by treatment arm (control, research arm, and dropped arm) in all patients.
Extended Data Fig. 5
Extended Data Fig. 5. Additional Kaplan-Meier curves of survival endpoints (part 3).
Relapse free survival (A), overall survival (B), and distant disease-free survival (C) by treatment arm [control, research arm (gap-scheduled), and dropped arm (non-gap-scheduled)) in patients who were assessed at stage II.
Extended Data Fig. 6
Extended Data Fig. 6. EQ-5D-5L visual analogue scale (VAS) scores and FACT-B total scores.
Least-squares mean change from baseline of EQ-5D-5L visual analogue scale (VAS) score (A), FACT-B total score (B) and FACT-B subscales with trial outcome index and FACT-B total score at 4 months and 6 months. Asterisk indicates a statistical difference between the treatment arms of p < 0.05 based on two-tailed t-test with Tukey’s adjustment for multiple comparisons. Error bars, 95% CI of the estimated change score.
Extended Data Fig. 7
Extended Data Fig. 7. Central pathology review Case Report Form.
Central pathology review Case Report Form.
See this image and copyright information in PMC

References

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