Efficacy and Safety of Immune Checkpoint Blockade in Patients With Li-Fraumeni Syndrome.

A case series evaluating efficacy and safety of immune checkpoint blockade in Li-Fraumeni syndrome.

Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in DSRCTs.

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1::WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on 12 samples from five patients, we find that DSRCT tumor cells cluster into consistent subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs. In vitro modeling shows that high EWSR1::WT1 DNA-binding activity associates with most lineage-related states, in contrast to glycolytic and profibrotic states. Single-cell chromatin accessibility analysis suggests that EWSR1::WT1 binding site variability may drive distinct lineage-related transcriptional programs, supporting some level of cell-intrinsic plasticity. Spatial transcriptomics reveals that glycolytic and profibrotic states specifically localize within hypoxic niches at the periphery of tumor cell islets, suggesting an additional role of tumor cell-extrinsic microenvironmental cues. We finally identify a single-cell transcriptomics-derived epithelial signature associated with improved patient survival, highlighting the clinical relevance of our findings.

TP53-associated early breast cancer: new observations from a large cohort.

BACKGROUND: A large well-annotated recent international cohort of Li-Fraumeni (LFS) patients with early-stage breast cancer (BC) was examined for shared features. METHODS: This multicentre cohort study included females with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic BC diagnosed between 2002-2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were utilized to summarize proportions and differences were assessed by Chi square or Wilcoxon rank sum tests. Metachronous contralateral breast cancer (CBC) risk, radiation-induced sarcoma risk, and recurrence-free survival (RFS) were analyzed by Kaplan-Meier methodology. RESULTS: Among 227 females who met study criteria, the median age of first BC diagnosis was 37 years (range 21-71), 11.9% presented with bilateral synchronous BC and 18.1% had ductal carcinoma in situ (DCIS) only. In total, 166 (73.1%) underwent mastectomies including 67 bilateral mastectomies as first BC surgery. Among those with retained breast tissue, CBC rate was 25.3% at 5-years. Among 186 invasive tumors, 72.1% were stages I-II, 48.9% node-negative, and the most common subtypes were HR+/HER2- (40.9%) and HR+/HER2 + (34.4%). At a median follow-up of 69.9 months (IQR 32.6-125.9), invasive HR+/HER2- disease had the highest recurrence risk among the subtypes (5-year RFS 61.1%, p = .0012). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. CONCLUSION: We observed high rates of DCIS, HR+ and HER2+ breast cancers, with a worse outcome in the HR+/HER2- luminal tumors despite appropriate treatment. Confirmation of these findings in further studies could have implications for BC care in LFS.

A Comprehensive Review on the Role of Lurbinectedin in Soft Tissue Sarcomas.

OPINION STATEMENT: Soft tissue sarcoma (STS), a substantial group of aggressive and rare tumors with tissue heterogeneity, is infrequently represented in clinical trials with an urgent necessity for newer treatment options. Lurbinectedin, an analog of trabectedin, is currently approved, in various countries, as a single agent, for the treatment of patients with relapsed small cell lung cancer (SCLC). However, preclinical and phase I and phase II trials have demonstrated the efficacy of lurbinectedin in different tumor types, including STS. The better understanding of the pathophysiology and evolution of STS as well as the mechanism of action of lurbinectedin in addition to the available data regarding the activity of this drug in this subset of patients will pave the way to newer therapeutic options and strategies.

Desmoid-type fibromatosis: Current therapeutic strategies and future perspectives.

Desmoid tumors (DT) are rare, slow-growing, locally invasive soft tissue tumors that often pose significant therapeutic challenges. Traditional management strategies including active surveillance, surgery, radiotherapy, and systemic therapy which are associated with varying recurrence rates and high morbidity. Given the challenging nature of DT and the modest outcomes associated with current treatment strategies, there has been a growing interest in the field of γ-secretase inhibitors as a result of its action on the Wnt/ß-catenin signaling pathway. In this review article, we will shed the light on the pathogenesis and molecular biology of DT, discuss its symptoms and diagnosis, and provide a comprehensive review of the traditional therapeutic approaches. We will also delve into the mechanisms of action of γ-secretase inhibitors, its efficacy, and the existing preclinical and clinical data available to date on the use of these agents, as well as the potential challenges and future prospects in the treatment landscape of these tumors.

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial.

BACKGROUND: The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. METHODS: In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). RESULTS: 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death. CONCLUSION: HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.

Systemic Therapy in Advanced Pleomorphic Liposarcoma: a Comprehensive Review.

OPINION STATEMENT: The therapeutic approach of pleomorphic liposarcoma (PLPS), a rare high-grade subgroup of soft tissue sarcoma, is commonly extrapolated from the management of other LPS subtypes. Only published retrospective data on PLPS currently serve as a guide for oncologists without clear recommendations or specific guidelines. In the advanced setting, specific systemic therapy such as eribulin and trabectedin showed promising activity in comparison to conventional therapy (doxorubicin- and gemcitabine-based protocols), which currently remains the current standard of care at initial stages of the disease. The better understanding of soft tissue sarcoma (STS) pathophysiology and disease course has led to the development of adapted clinical trial designs for rare STS histotypes with specific treatment approach.

Evolution of Patterns of Care and Outcomes in the Real-Life Setting for Patients with Metastatic GIST Treated in Three French Expert Centers over Three Decades.

Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized by KIT or PDGFRA mutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in the three national coordinating centers of NetSarc, the French network of sarcoma referral centers endorsed by the National Institute of Cancers, from 1990 to 2018. The primary objective was to describe the clinical and biological profiles as well as the treatment modalities of patients with metastatic GIST in a real-life setting, including access to clinical trials and LR procedures in the metastatic setting. Secondary objectives were to assess (1) patients' outcome in terms of time to next treatment (TNT) for each line of systemic treatment, (2) patients' overall survival (OS), (3) evolution of patients' treatment modalities and OS according to treatment access: <2002 (pre-imatinib approval), 2002-2006 (pre-sunitinib approval), 2006-2014 (pre-regorafenib approval), post 2014, and (4) the impact of clinical trials and LR procedures on TNT and OS in the metastatic setting. 1038 patients with a diagnosis of GIST made in one of the three participating centers between 1990 and 2018 were included in the national prospective database. Among them, 492 patients presented metastasis, either synchronous or metachronous. The median number of therapy lines in the metastatic setting was 3 (range 0-15). More than half of the patients (55%) participated in a clinical trial during the course of their metastatic disease and half (51%) underwent additional LR procedures on metastatic sites. The median OS in the metastatic setting was 83.4 months (95%CI [72.7; 97.9]). The median TNT was 26.7 months (95%CI [23.4; 32.3]) in first-line, 10.2 months (95%CI [8.6; 11.8]) in second line, 6.7 months (95%CI [5.3; 8.5]) in third line, and 5.5 months (95%CI [4.3; 6.7]) in fourth line, respectively. There was no statistical difference in OS in the metastatic setting between the four therapeutic periods (log rank, p = 0.18). In multivariate analysis, age, AFIP Miettinen classification, mutational status, surgery of the primary tumor, participation in a clinical trial in the first line and LR procedure to metastatic sites were associated with longer TNT in the first line, whereas age, mitotic index, mutational status, surgery of the primary tumor and LR procedure to metastatic sites were associated with longer OS. This real-life study advocates for early reference of metastatic GIST patients to expert centers to orchestrate the best access to future innovative clinical trials together with LR strategies and further improve GIST patients' survival.

Contribution of collegial support meetings (CSM) in the management of complex situations of patients with advanced cancer.

PURPOSE: Collegial support meetings (CSM) have been set up in the Gustave Roussy Cancer Center for inpatients whose complex care requires a multi-professional approach involving many participants: oncologists but also health-caregivers, a member of the palliative care team, an intensivist, and a psychologist. This study is aimed at describing the role of this newly multidisciplinary meeting implemented in a French Comprehensive Cancer Center. METHODS: Each week, the health-caregivers decide which situations should be examined, depending on the difficulty of a case. The discussion goes on to include the goal of treatment, the intensity of care, ethical and psychosocial issues, and the patient's life plan. Finally, to obtain feedback from the teams, a survey has been distributed to assess the interest in the CSM. RESULTS: In 2020, 114 inpatients were involved, and 91% were in an advanced palliative situation. During the CSMs, 55% of the discussions focused on whether to continue specific cancer treatment-29% about whether to continue invasive medical care-50% about optimizing supportive care. We estimate that between 65 and 75% of CSMs influenced further decisions. Death occurred during the hospitalization for 35% of the patients that were discussed. The lapse of time between last chemotherapy and death was 24 days (IQR, 28.5). CSMs were well received, since 80% of the teams find these meetings useful. CONCLUSIONS: CSMs reach conclusions for medical and nursing staff involved, in order to improve the management of inpatients with cancer in advanced palliative situation and to define the better goals of care.

Pain in desmoid-type fibromatosis: Prevalence, determinants and prognosis value.

The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.

[2022: New therapeutic practices in breast oncology]. / 2022 : nouvelles pratiques thérapeutiques en oncologie mammaire.

In women, breast cancer is both the most common and the deadliest. In 2018, an estimated 58,459 new cases were diagnosed in France, and 12,146 patients died. While these figures are impressive, it should be borne in mind that patient survival after treatment for breast cancer has improved significantly and is now 87 % at five years (nearly nine out of ten women), up from 80 % in 1993. This progress is due to the different weapons available to patients and the development of new therapies such as immunotherapy or drug-conjugated antibodies. The classification of breast cancers is also evolving, in particular through the identification of biomarkers that enable the therapeutic strategy to be refined (PD-L1, BRCA…). New anti-HER2 molecules, such trastuzumab deruxtecan, have shown very promising therapeutic activity in patients with breast cancer with low HER2 expression. The search for the BRCA constitutional mutation helps to optimise management. The use of pembrolizumab in the metastatic setting is now possible in tumours expressing PD-L1 with a threshold expression of the PD-L1 marker of CPS ≥ 10. In addition, late 2021/early 2022 has provided evidence that collaboration between physicians and patient networks facilitates better access to treatment. This review presents advances in adjuvant and metastatic breast cancer presented at ASCO and ESMO in 2022.

Single-agent gemcitabine in patients with advanced, pre-treated angiosarcoma: A multicenter, retrospective study.

Gemcitabine has shown clinical activity against angiosarcoma in small series, alone, or combined with taxanes. We aimed to evaluate its activity as a single-agent in a larger series of patients with advanced angiosarcoma. We retrospectively reviewed the electronic medical records of consecutive adult patients with advanced angiosarcoma treated with single-agent gemcitabine at our institutions from January 2010 to January 2021. Response was evaluated according to RECIST 1.1, and toxicity was graded according to NCI-CTC v5.0. 42 patients were identified. 38 patients (90%) had received prior anthracyclines and weekly paclitaxel, and 9 (21%) had received pazopanib. The best tumor response was partial response (PR) in 16 patients (38%), or stable disease (10 patients, 24%). All 8 patients with cardiac angiosarcoma experienced a PR. Median PFS was 5.4 months (95%CI: 3.1-6.5), and median OS was 9.9 months (95%CI: 6.6-13.4). Single-agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma.

A novel fusion variant LSM14A::NR4A3 in extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue neoplasm of uncertain lineage characterized by the pathognomonic rearrangement of the NR4A3 gene, which in most cases is fused with EWSR1. Other NR4A3 fusion partners have been described, namely TAF15, FUS, TCF12, and TGF. Some studies suggest that EMCs with non-EWSR1 variant fusion are associated with high-grade morphology and worst clinical behavior compared to EWSR1::NR4A3 tumors, supporting the potential significance of particular fusion variant in EMC. We report a case of a 34-year-old male who presented with calf EMC and subsequently developed a slowly progressive metastatic disease 3 years after diagnosis. Whole-transcriptome analysis with total RNA sequencing enabled identification of a novel fusion transcript LSM14A::NR4A3, expanding the molecular spectrum of EMC.

The Molecular Predictive and Prognostic Biomarkers in Metastatic Breast Cancer: The Contribution of Molecular Profiling.

The past decade was marked by several important studies deciphering the molecular landscape of metastatic breast cancer. Although the initial goal of these studies was to find driver oncogenic events to explain cancer progression and metastatic spreading, they have also permitted the identification of several molecular alterations associated with treatment response or resistance. Herein, we review validated (PI3KCA, ESR1, MSI, NTRK translocation) and emergent molecular biomarkers (ERBB2, AKT, PTEN, HRR gene, CD274 amplification RB1, NF1, mutational process) in metastatic breast cancer, on the bases of the largest molecular profiling studies. These biomarkers will be classed according the level of evidence and, if possible, the ESCAT (ESMO) classification. Finally, we will provide some perspective on development in clinical practice for the main biomarkers.

Favorable safety profile of moderate hypofractionated over normofractionated radiotherapy in breast cancer patients: a multicentric prospective real-life data farming analysis.

BACKGROUND: Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe and efficient as normofractionated radiotherapy (NFRT) in randomized trials resulting in major changes in clinical practice. Toxicity rates observed in selected clinical trial patients may differ from those observed in unselected patients with possible comorbidities and frailty in real-life. This study aimed to examine the influence of HFRT versus NFRT on acute toxicity and identify risks factors of dermatitis in real-life patients. MATERIALS AND METHODS: Prospective data from breast cancer patients, treated with locoregional radiotherapy were collected between November 2015 and February 2020 in 3 comprehensive cancer centers. Through a systematic data-farming strategy, acute toxicity evaluation forms (CTCAEv4.0) were prospectively completed and extracted electronically. The results from each center were then anonymously merged into a single database for analysis. A Chi-2 test was used to compare HFRT and NFRT. Furthermore, risk factors of dermatitis were identified in a sub-study (622 patients) by multivariate logistic regression analysis. RESULTS: In total, 3518 T0-4 N0-3 mostly M0 (85.8%) breast cancer patients with a median age of 60.7 (24-96 years old) were analyzed. Acute grade 2-3 dermatitis, grade 1-3 breast oedema, and grade 1-2 hyperpigmentation were less frequent with HFRT versus NFRT: respectively 8.9% versus 35.1% (Chi-2 = 373.7; p < 0.001), 29.0% versus 37.0% (Chi-2 = 23.1; p < 0.001) and 27.0% versus 55.8% (Chi-2 = 279.2; p < 0.001). Fewer patients experienced pain with HFRT versus NFRT: 33.4% versus 53.7% respectively (Chi-2 = 137.1; p < 0.001). Factors such as high BMI (OR = 2.30 [95% CI, 1.28-4.26], p < 0.01), large breast size (OR = 1.88 [95% CI, 1.07-3.28], p < 0.01) and lumpectomy over mastectomy (OR = 0.52 [95% CI, 0.27-0.97], p < 0.05) were associated with greater risk factors of grade 2-3 dermatitis in multivariate analysis regardless of NFRT or HFRT. CONCLUSION: The results of this study suggests that breast HFRT may be a better option even for patients with a high BMI or large breast size. Acute toxicity was low to mild, and lower with HFRT compared to NFRT. Results from real-life data were robust, and support the use of HFRT beyond randomized study populations. Long-term real-life data awaits further investigation.

Clinicopathological characteristics and prognosis of breast cancer patients with isolated central nervous system metastases in the multicentre ESME database.

BACKGROUND: As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations. METHODS: We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Descriptive statistics and multivariate Cox model were used. RESULTS: Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50-1.91), p < 0.001). Among the 541 (2.4%) patients with isolated CNS metastases and no intrathecal therapy (excluding leptomeningeal metastases), HER2+ cases were preponderant over TN or HR+ /HER2- cases (41.6% versus 26.1% versus 28.5%, respectively, p < 0.01). The treatment strategy consisted of a combination of local treatment and systemic therapy (49.2%), local treatment only (35.5%) or systemic therapy only (11.4%), or symptomatic therapy only (3.9%). Median PFS was 6.1 months (95% CI: 5.7-6.8). Median OS was 20.7 months (95% CI: 17.3-24.3), reaching 37.9 months (95% CI: 25.9-47.6) in the HR+ /HER2+ subgroup. Older age, TN subtype, MBC-free interval of 6-12 months, lower performance status, and WBRT were associated with poorer survival. Patients who received systemic therapy within 3 months from MBC diagnosis had longer OS (24.1 versus 16.1 months, p = 0.031), but this was not significant on multivariate analysis [HR = 1.0 (95% CI: 0.7-1.3), p = 0.806]. CONCLUSIONS: Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies.

Chemotherapy in the management of periosteal osteosarcoma: A narrative review.

Periosteal osteosarcoma (PO), an intermediate-grade chondroblastic osteosarcoma (OST) arising from the surface of the bones, is a rare histological subtype among primary bone sarcomas, most commonly diagnosed in young patients. It is characterized by distinct specific radiological and pathological features. The current management strategy is based on several case reports and series, without any solid international recommendations. Most sarcoma experts agree on the crucial role of an optimal complete surgical approach. However, with the paucity of available reports, the role of systemic treatment and its timing remains debatable. With this paper, we will review the available data on the actual impact of chemotherapy in PO patients with emphasis on the radiological, pathological, and therapeutic characteristics of this rare entity.

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume?

AIM: To prospectively assess toxicities of curative-intent intensity-modulated conformal radiotherapy (IMRT) in patients with extremity soft tissue sarcomas (ESTS). METHODS: Data from 59 consecutive patients with ESTS between 2014 and 2019 were both retrospectively and prospectively analysed. Toxicity data were collected both by confidential mailed survey (39% completed) and medical charts, and graded according to CTCAE v5.0. Normal tissues dosimetric data (healthy soft tissue segment, joint and bone) were included. The healthy soft tissue segment was created by adding 5 cm on either side of the PTV on CT axial slices, the PTV and bone (and articulation if present) were then removed from the generated volume. RESULTS: IMRT was delivered post-operatively for nearly half of patients (n = 24, 41%), preoperatively for 18 (31%) and exclusively for 17 (28%; salvage: 13% or immediately inoperable: 15%). The median total dose delivered to the planned target volume (PTV) was 50.4 Gy (36-68 Gy) and 13 patients (22%) received a boost. With a median follow-up of 27 months (6-94 months), a total of 87 late effects were identified in 44/59 (75%) patients: 89% G1-2, and 11% G3-4. The main G1-2 toxicities were: functional limitation (36%), oedema (29%), gait disorders (20%), neurological disorders (20%) and chronic pain (32%). G3-4 toxicities were pain (n = 2), arterial stricture (n = 1) and a chronic wound requiring skin graft (n = 2). No bone fracture was observed. Quality of life was rated as good or very good in 70% patients who completed the survey. Larger (>3500 cm3) healthy soft tissue segment volume was associated with decreased late toxicities (p = 0.02). No other predictive factor of toxicity was identified. The 2-year rates of local control, overall survival and recurrence-free survival were 90%, 90% and 64%, respectively. CONCLUSION: Healthy soft tissue segment volume influenced toxicity. Long-term prospective monitoring in a homogeneous population remains critical to assess the impact of IMRT induced chronic toxicity in ESTS patients. This should ideally lead to a validated normal tissue dose constraint (e.g.: healthy soft tissue segment volume > 3500 cm3) to recommend for practitioners to help reduce the late toxicity risk.

Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial.

The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg-1 every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00-1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54-1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30-0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12-1.13) for patients with PD-L1+ TNBC (n = 32) and 0.49 (95% CI: 0.18-1.34) for those with PD-L1- TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05-0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42-2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.