L Gianni1, C S Huang2, D Egle3, B Bermejo4, C Zamagni5, M Thill6, A Anton7, S Zambelli8, G Bianchini8, S Russo9, E M Ciruelos10, R Greil11, V Semiglazov12, M Colleoni13, C Kelly14, G Mariani15, L Del Mastro16, I Maffeis17, P Valagussa17, G Viale18. 1. Fondazione Michelangelo, Milan, Italy. Electronic address: luca.gianni@fondazionemichelangelo.org. 2. National Taiwan University Hospital and Taiwan Breast Cancer Consortium, Taipei, Taiwan. 3. Department of Gynecology, Brust Gesundheit Zentrum Tirol, Medical University Innsbruck, Innsbruck, Austria. 4. Hospital Clinico Universitario, Valencia, Spain. 5. Addarii Medical Oncology IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 6. Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany. 7. Hospital Universitario Miguel Servet, Zaragoza, Spain. 8. San Raffaele Hospital, Milano, Italy. 9. Department of Oncology, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy. 10. Hospital Universitario 12 de Octubre, Madrid, Spain. 11. 3rd Medical Department, Paracelsus Medical University Salzburg, Salzburg, Austria; Salzburg Cancer Research Institute-CCCIT, Salzburg, Austria; Cancer Cluster Salzburg, Salzburg, Austria. 12. NN Petrov Research Institute of Oncology, St. Petersburg, Russia. 13. IEO, Istituto Europeo di Oncologia, IRCCS, Milan, Italy. 14. Trinity St James's Cancer Institute, St James's Hospital, Dublin, Ireland. 15. Istituto Nazionale Tumori, Milan, Italy. 16. IRCCS Ospedale Policlinico San Martino, UO Breast Unit, Genoa, Italy; Università di Genova, Dipartimento di Medicina Interna e Specialità Mediche (Di.M.I.), Genoa, Italy. 17. Fondazione Michelangelo, Milan, Italy. 18. IEO, Istituto Europeo di Oncologia, IRCCS, Milan, Italy; University of Milan, Milan, Italy.
Abstract
BACKGROUND: High-risk triple-negative breast cancers (TNBCs) are characterized by poor prognosis, rapid progression to metastatic stage and onset of resistance to chemotherapy, thus representing an area in need of new therapeutic approaches. Programmed death-ligand 1 (PD-L1) expression is an adaptive mechanism of tumour resistance to tumour-infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, available data support the concept that blockade of PD-L1/programmed cell death protein 1 checkpoint may improve efficacy of classical chemotherapy. PATIENTS AND METHODS: Two hundred and eighty patients with TNBC were enrolled in this multicentre study (NCT002620280) and randomized to neoadjuvant carboplatin area under the curve 2 and nab-paclitaxel 125 mg/m2 intravenously (i.v.) on days 1 and 8, without (n = 142) or with (n = 138) atezolizumab 1200 mg i.v. on day 1. Both regimens were given q3 weeks for eight cycles before surgery followed by four cycles of an adjuvant anthracycline regimen. The primary aim of the study was to compare event-free survival (EFS), and an important secondary aim was the rate of pathological complete response (pCR defined as the absence of invasive cells in breast and lymph nodes). The primary population for all efficacy endpoints is the intention-to-treat (ITT) population. RESULTS: The ITT analysis revealed that pCR rate after treatment with atezolizumab (48.6%) did not reach statistical significance compared to no atezolizumab [44.4%: odds ratio (OR) 1.18; 95% confidence interval 0.74-1.89; P = 0.48]. Treatment-related adverse events were similar with either regimen except for a significantly higher overall incidence of serious adverse events and liver transaminase abnormalities with atezolizumab. CONCLUSIONS: The addition of atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pCR in women with TNBC. In multivariate analysis, the presence of PD-L1 expression was the most significant factor influencing the rate of pCR (OR 2.08). Continuing follow-up for the EFS is ongoing, and molecular studies are under way.
BACKGROUND: High-risk triple-negative breast cancers (TNBCs) are characterized by poor prognosis, rapid progression to metastatic stage and onset of resistance to chemotherapy, thus representing an area in need of new therapeutic approaches. Programmed death-ligand 1 (PD-L1) expression is an adaptive mechanism of tumour resistance to tumour-infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, available data support the concept that blockade of PD-L1/programmed cell death protein 1 checkpoint may improve efficacy of classical chemotherapy. PATIENTS AND METHODS: Two hundred and eighty patients with TNBC were enrolled in this multicentre study (NCT002620280) and randomized to neoadjuvant carboplatin area under the curve 2 and nab-paclitaxel 125 mg/m2 intravenously (i.v.) on days 1 and 8, without (n = 142) or with (n = 138) atezolizumab 1200 mg i.v. on day 1. Both regimens were given q3 weeks for eight cycles before surgery followed by four cycles of an adjuvant anthracycline regimen. The primary aim of the study was to compare event-free survival (EFS), and an important secondary aim was the rate of pathological complete response (pCR defined as the absence of invasive cells in breast and lymph nodes). The primary population for all efficacy endpoints is the intention-to-treat (ITT) population. RESULTS: The ITT analysis revealed that pCR rate after treatment with atezolizumab (48.6%) did not reach statistical significance compared to no atezolizumab [44.4%: odds ratio (OR) 1.18; 95% confidence interval 0.74-1.89; P = 0.48]. Treatment-related adverse events were similar with either regimen except for a significantly higher overall incidence of serious adverse events and liver transaminase abnormalities with atezolizumab. CONCLUSIONS: The addition of atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pCR in women with TNBC. In multivariate analysis, the presence of PD-L1 expression was the most significant factor influencing the rate of pCR (OR 2.08). Continuing follow-up for the EFS is ongoing, and molecular studies are under way.
Authors: Ilana Schlam; Paolo Tarantino; Stefania Morganti; Filipa Lynce; Dario Trapani; Erica L Mayer; Ana C Garrido-Castro; Ada Waks; Sara M Tolaney Journal: Drugs Date: 2022-10-07 Impact factor: 11.431
Authors: Vladimir Semiglazov; Andrey Tseluiko; Asel Kudaybergenova; Anna Artemyeva; Petr Krivorotko; Roman Donskih Journal: Cancer Biol Med Date: 2022-06-09 Impact factor: 5.347