Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Neoadjuvant pembrolizumab+chemotherapy vs placebo+chemotherapy, followed by adjuvant pembrolizumab vs placebo for early-stage TNBC: event-free survival sensitivity and subgroup analyses from KEYNOTE-522 (#189)

Peter Schmid 1 , Javier Cortes 2 , Rebecca Dent 3 , Lajos Pusztai 4 , Heather McArthur 5 , Sherko Kümmel 6 , Jonas Bergh 7 , Carsten Denkert 8 , Yeon Hee Park 9 , Rina Hui 10 , Nadia Harbeck 11 , Masato Takahashi 12 , Michael Untch 13 , Peter A. Fasching 14 , Fatima Cardoso 15 , Jay Andersen 16 , Debra Patt 17 , Michael Danso 18 , Marta Ferreira 19 , Marie-Ange Mouret-Reynier 20 , Seock-Ah Im 21 , Jin Hee Ahn 22 , Maria Gion 23 , Sally Baron-Hay 24 , Jean-Francois Boileau 25 , Yalin Zhu 26 , Wilbur Pan 26 , Konstantinos Tryfonidis 26 , Vassiliki Karantza 26 , Joyce O’Shaughnessy 27
  1. Barts Cancer Institute, Queen Mary University London, London, UK
  2. International Breast Cancer Center, Quironsalud Group; Vall d'Hebron Institute of Oncology (VHIO), Madrid & Barcelona, Spain and Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain
  3. National Cancer Center Singapore, Duke-NUS Medical School, Singapore
  4. Yale School of Medicine, Yale Cancer Center, New Haven, CT, USA
  5. University of Texas Southwestern Medical Center, Dallas, TX, USA
  6. Kliniken Essen-Mitte, Essen, Germany and Charité – Universitätsmedizin Berlin, Department of Gynecology with Breast Center, Berlin, Germany
  7. Department of Oncology-Pathology, Karolinska Institutet and Breast Cancer Centre, Cancer theme, Karolinska University Hospital, Solna, Sweden
  8. Institute of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), , Marburg, Germany
  9. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  10. Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia
  11. Breast Center, Department of Obstetrics and Gynecology and CCC Munich, LMU University Hospital, Munich, Germany
  12. Hokkaido Cancer Center, Sapporo, Japan
  13. Breast Cancer Center, HELIOS Klinikum Berlin-Buch GmbH, Berlin, Germany
  14. University Hospital Erlangen, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  15. Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal
  16. Compass Oncology, The US Oncology Network, Portland, OR, USA
  17. Texas Oncology, The US Oncology Network, Austin, TX, USA
  18. Virginia Oncology Associates, The US Oncology Network, Norfolk, VA, USA
  19. Instituto Português de Oncologia do Porto Francisco Gentil (IPO-Porto), Porto, Portugal
  20. Centre Jean-Perrin, Clermont-Ferrand, France
  21. Seoul National University, Seoul, Republic of Korea
  22. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  23. Ramon y Cajal University Hospital, Madrid, Spain
  24. Royal North Shore Hospital, St. Leonards, NSW, Australia
  25. McGill University, Jewish General Hospital Segal Cancer Centre, Montréal, Québec, Canada
  26. Merck & Co., Inc., Rahway, NJ, USA
  27. Baylor University Medical Center, Texas Oncology, The US Oncology Network, Dallas, TX, USA

Aims: The phase 3 KEYNOTE-522 (NCT03036488) study primary analysis showed significantly longer event-free survival (EFS) with neoadjuvant pembrolizumab+chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant chemotherapy alone in patients with early-stage TNBC (HR, 0.63 [95% CI, 0.48‒0.82]; P<0.001).1 We present prespecified sensitivity and subgroup analyses for EFS.

Methods: Patients with previously untreated, non-metastatic TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to pembrolizumab 200 mg Q3W or placebo, both given with 4 cycles of paclitaxel+carboplatin, then with 4 cycles of doxorubicin or epirubicin+cyclophosphamide (neoadjuvant). After definitive surgery, patients received pembrolizumab or placebo for 9 cycles or until recurrence/unacceptable toxicity (adjuvant). Dual primary endpoints: pCR rate and EFS. Five prespecified sensitivity analyses for EFS were performed and treatment effects on EFS were examined in prespecified patient subgroups.

Results: 1174 patients were randomized (pembrolizumab+chemotherapy, n=784; placebo+chemotherapy, n=390). At data cutoff (March 23, 2021), median follow-up was 39.1 months. EFS HRs (95% CIs) for neoadjuvant pembrolizumab+chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant chemotherapy alone were, for sensitivity analyses using alternative censoring rules: 0.64 (0.48‒0.84); and using modified EFS definitions: “new anticancer therapy for metastatic disease” considered EFS event, 0.63 (0.48‒0.82); “positive margin at last surgery” removed, 0.65 (0.50‒0.85) ; “positive margin at last surgery” and “second primary malignancy” removed, 0.63 (0.48‒0.84); “second breast malignancy” included, 0.63 (0.48‒0.82). EFS HRs (95% CIs) for subgroups: nodal involvement positive, 0.65 (0.46‒0.91) or negative, 0.58 (0.37‒0.91); disease stage II, 0.60 (0.42‒0.86]) or III, 0.68 (0.45‒1.03); pre-menopausal, 0.62 (0.42‒0.91) or post-menopausal, 0.64 (0.44‒0.93); HER2 status 2+ by IHC but FISH-, 0.73 (0.43‒1.24) or 0-1+ by IHC, 0.60 (0.44‒0.82); and LDH >ULN, 0.65 (0.37‒1.12) or ≤ULN, 0.63 (0.46‒0.86).

Conclusions: EFS sensitivity analyses showed robust treatment benefit of neoadjuvant pembrolizumab+chemotherapy followed by adjuvant pembrolizumab for previously untreated non-metastatic TNBC, which was generally consistent across patient subgroups evaluated.

  1. Schmid P, et al. N Engl J Med 2022;386:556-67.