Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial

Nat Med. 2024 Jan;30(1):249-256. doi: 10.1038/s41591-023-02677-x. Epub 2024 Jan 8.

Abstract

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n = 353; experimental arm) versus placebo and nab-P (n = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470-0.906, P = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414-0.914, P = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 .

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III

MeSH terms

  • Albumins*
  • Antibodies, Monoclonal, Humanized*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • B7-H1 Antigen / therapeutic use
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Paclitaxel / adverse effects
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • 130-nm albumin-bound paclitaxel
  • toripalimab
  • B7-H1 Antigen
  • Paclitaxel
  • Albumins
  • Antibodies, Monoclonal, Humanized

Associated data

  • ClinicalTrials.gov/NCT03777579