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Background: Triple negative breast cancers of high proliferation or grade are a subgroup characterized by very poor prognosis, rapid progression to metastatic stage and rapid onset of resistance to chemotherapy after initial response. As a whole, triple negative breast cancer (TNBC) represents a specific area of medical need, in which new therapeutic approaches deserve appropriate test. Retrospective data showed that a subset of patients have an ongoing immune response within the tumor microenvironment, and that PD-L1 expression is an adaptive method of tumor resistance to tumor infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, the data suggests a role for immune regulation of response to chemotherapy, and support the concept that blockade of immune check-points may favor the achievement of durable response by immune mechanisms themselves, and in combination with classical chemotherapy. Methods: In this multicenter open label study (NCT002620280), a total of 280 patients with TNBC were randomized to neoadjuvant carboplatin AUC 2 and abraxane 125 mg/m2 iv on days 1 and 8, with or without atezolizumab 1200 mg iv on day 1. Both regimens were given every 3 weeks for 8 cycles and were followed by surgery and by 4 cycles of an anthracycline regimen as per investigator choice. The primary aim of the study is to compare event-free survival 5 years after randomization of the last patient. Important secondary aim is the rate of pCR (defined as absence of invasive in breast and lymph nodes). The comparison among treatments will be carried out by a two-sided Cochran-Mantel-Haenszel test, controlling for disease stage (early high-risk vs locally advanced) and PD-L1 expression (positive vs negative). The primary population for all efficacy endpoints will be the ITT (intent-to-treat) population, the safety population is defined as all randomized patients who received at least one dose of either regimen. pCR and safety data will be presented at the meeting. Patients will continue to be followed up to allow for assessing comparative long-term event-free and overall survival analyses. Supported in part by unrestricted grants from Hoffman-La Roche, Ltd, Switzerland and Celgene International Sarl, Switzerland Citation Format: Luca Gianni, Chiun-Sheng Huang, Daniel Egle, Begona Bermejo, Claudio Zamagni, Marc Thill, Antonio Anton, Stefania Zambelli, Giampaolo Bianchini, Stefania Russo, Eva Ciruelos, Richrad Greil, Vladimir Semiglazov, Marco Colleoni, Catherine Kelly, Gabriella Mariani, Lucia Del Mastro, Ilaria Maffeis, Pinuccia Valagussa, Giuseppe Viale. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS3-04.

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Northern Italy has been one of the European regions reporting the highest number of COVID-19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID-19-positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID-19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer-related outcome. In this article, we attempt to estimate the individual riskbenefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID-19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. The Oncologist 2020;25:1-8 Implications for Practice: Managing patients with breast cancer during the COVID-19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID-19-related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients' and health workers' psychological distress.

Background: Several studies show that the presence of TILs has prognostic significance in TNBC, with greater lymphocytic infiltration associated with clinical outcomes. In the phase 2 KEYNOTE-086 study, TIL levels were a surrogate marker of preexisting antitumor immunity and were independent predictors of response to pembrolizumab (pembro) monotherapy. Here, we analyzed the relationship between the presence of TILs and outcomes in the phase 3 KEYNOTE-119 (NCT02555657) study of pembro monotherapy vs single-agent chemotherapy (chemo) in patients (pts) with previously treated mTNBC. Methods: From October 2015 to April 2017, 622 pts from 31 countries were enrolled. Key eligibility criteria included centrally confirmed TNBC, 1 or 2 prior systemic treatments for metastatic disease, documented progression on most recent therapy, prior treatment with an anthracycline and/or a taxane, and provision of a tumor sample for central determination of triple-negative status and PD-L1 expression. Pts with active brain metastases were excluded. Pts were stratified by PD-L1 status (positive vs negative; PD-L1 positivity was defined as a CPS ≥1) and history of prior neoadjuvant/adjuvant treatment vs de novo metastatic disease at initial diagnosis. Pts were randomly assigned 1:1 to pembro 200 mg Q3W or single-agent chemo per investigator’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine, with a maximum enrollment cap of 60% for each, administered per local product label, until progression, intolerable toxicity, or investigator/patient decision. Response was assessed every 9 wk for 1 y and every 12 wk thereafter. Primary end points were OS in the PD-L1 CPS ≥10, CPS ≥1, and total populations. Secondary end points were PFS, ORR, duration of response, and DCR in the PD-L1 CPS ≥10, CPS ≥1, and total populations, and safety. The presence of TILs in archival tumor samples was assessed by light microscopy of hematoxylin and eosin-stained sections using a predefined method. The relationship between TILs and OS and PFS was analyzed using Cox regression; the relationship between TILs and ORR was analyzed using logistic regression. The interaction between treatment and TILs was assessed. Results: The study was negative for the primary end point. TILs were evaluable in 536/622 (86.2%) treated pts (273 [pembro]; 263 [chemo]). The median TILs distribution was 5% (IQR, 14%). TIL levels were significantly higher in responders vs nonresponders in the pembro arm, but not the chemo arm. TIL levels as a continuous variable were significantly (P< 0.05) associated with all clinical outcomes tested in the pembro but not the chemo arm (Table). For pts with TILs <5%, assessment of OS yielded a HR of 1.50 (95% CI, 1.14-1.97); for pts with TILs ≥5%, the HR was 0.75 (95% CI, 0.59-0.96). Median OS and 18-month OS rate (pembro vs chemo) for pts with TILs <5% was 5.9 vs 8.8 mo and 15% vs 27%, respectively; for pts with TILs ≥5%, this was 12.5 vs 11.3 mo and 35% vs 27%. The correlation between TILs vs CPS was moderate at 0.45; multivariate modeling of TILs and CPS showed independent predictive value. Conclusions: High TILs were significantly associated with better clinical outcomes with pembro but not chemo. Efficacy estimates at the prespecified median TIL cut point (≥5%) suggest that a subset of later-line advanced pts with TNBC can derive prolonged survival benefit from pembro over chemo. Association of TILs With Clinical OutcomesTreatment ArmContinuousBORDCRPFSOSVariableORRP*DCRP*Event RateP*Event RateP*Pembro (n=273),TILs25 (9.2)0.000732 (11.7)0.0058241 (88.3)0.0002239 (87.5)0.0001n (%)Chemo (n=263),TILs29 (11.0)0.180950 (19.0)0.3026191 (72.6)0.234236 (89.7)0.3321n (%)*P values are 1-sided for pembro and 2-sided for chemo.The stratification variable, prior (neo)adjuvant therapy vs de novo metastatic disease at initial diagnosis, was used as a covariate in the model.TILs was square root transformed.BOR, best overall response; chemo, chemotherapy; DCR, disease control rate; OS, overall survival; pembro, pembrolizumab; PFS, progression-free survival; TILs, tumor-infiltrating lymphocytes. Citation Format: Sherene Loi, Eric Winer, Oleg Lipatov, Seock-Ah Im, Anthony Goncalves, Javier Cortes, Keun S Lee, Peter Schmid, Laura Testa, Isabell Witzel, Shoichiro Ohtani, Nicholas Turner, Stefania Zambelli, Nadia Harbeck, Fabrice Andre, Rebecca Dent, LingKang Huang, Jaime Mejia, Vassiliki Karantza, Roberto Salgado. Relationship between tumor-infiltrating lymphocytes (TILs) and outcomes in the KEYNOTE-119 study of pembrolizumab vs chemotherapy for previously treated metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD5-03.