Neratinib as Extended Adjuvant Treatment of HER2-Positive/HR-Positive Early Breast Cancer Patients in Germany, Austria, and Switzerland: Interim Results of the Prospective, Observational ELEANOR Study.

Introduction: Prognosis of patients diagnosed with HER2+ early breast cancer (eBC) has substantially improved, but distant recurrences impacting quality of life and survival still occur. One treatment option for extended adjuvant treatment of patients with HER2+/HR+ eBC is neratinib, available in Europe for patients who completed adjuvant trastuzumab-based therapy within 1 year. The ELEANOR study is investigating the real-world use of neratinib in Germany, Austria, and Switzerland. Results from an interim analysis of the first 200 patients observed for ≥3 months are reported. Methods: The primary objective of this prospective, multicenter, observational study is to assess patient adherence to neratinib (defined as the percentage of patients taking neratinib on ≥75% prescribed days). Secondary objectives are patient characteristics and treatment outcomes. Results: At cut-off (May 2, 2022), a total of 202 patients had been observed for ≥3 months, with neratinib treatment documented for 187 patients (median age: 53.0 years; 67.9% at increased risk of disease recurrence). In total, 151 (80.7%) patients had received prior neoadjuvant treatment; of these, 82 (54.3%) patients achieved a pathologically complete response. Neratinib was initiated at a median 3.6 months after trastuzumab-based treatment, with 36.4% starting at a dose <240 mg/day. Treatment is ongoing for 46.0% of patients, with median treatment duration of 11.2 (interquartile range 0.9-12.0) months. Diarrhea was the most common adverse event (78.6% any grade, 20.3% grade ≥3); pharmacologic prophylaxis was used in 85.6% of patients. Conclusions: The pattern of anti-HER2 pretreatment observed reflected the current treatment for HER2+/HR+ eBC in Germany, Austria, and Switzerland. These interim results suggest that neratinib as an extended adjuvant is a feasible option after various anti-HER2 pretreatments and that its tolerability can be managed and improved with proactive diarrhea management.

Pharmacotherapy for leptomeningeal disease in breast cancer.

Clinical data supporting the best therapeutic approach in leptomeningeal disease (LMD; also known as leptomeningeal metastases or leptomeningeal carcinomatosis) are lacking. Despite the development of new agents and increasing incidence of central nervous system metastases, patients with LMD are often excluded from clinical trials in breast cancer, with very few conducted specifically in LMD. Consequently, current evidence may not provide an accurate reflection of real-world clinical practice. This review aims to provide further insight into the treatment strategies for patients with breast cancer and LMD. We explore differences between clinical and real-world studies, considering inclusion criteria, levels of evidence for LMD diagnosis, and time between diagnosis of LMD and LMD-specific treatment initiation. Patient prognosis is poor; median overall survival is limited to several months, with approximately 10% of patients alive at 12 months. Efficacy results have been reported for various systemic and intrathecal agents in LMD to date. Systemic therapies under investigation for LMD in breast cancer include tucatinib, trastuzumab deruxtecan, and paclitaxel trevatide; trastuzumab is the main intrathecal agent currently under investigation. Recent trials investigating systemic or intrathecal therapies are typically small, single-arm studies, and most are restricted to patients with human epidermal growth factor receptor 2-positive breast cancer. Moreover, the variability among inclusion criteria and response assessment tools makes the interpretation of results difficult. Large retrospective cohorts with various inclusion criteria and treatment regimens provide some real-world data. However, there remains an urgent need for randomised clinical trials which include patients with LMD across all breast cancer subtypes.

The impact of COVID-19 and socioeconomic status on psychological distress in cancer patients

Objective: We aimed to investigate the impact of the COVID-19 pandemic on psychological symptom burden against the socioeconomic background of cancer patients using data from routine assessments before and during the pandemic Method: In this cross-sectional study, standardised assessment instruments were applied in N = 1,329 patients to screen for symptoms of anxiety, depression, post-traumatic stress, and fatigue from 2018 to 2022. Two MANOVAs with post-hoc tests were computed. First, only time was included as predictor to examine the isolated impact of the pandemic. Second, income level and education level were included as further predictors to additionally test the predictive power of socioeconomic factors Results: In the final model, only income had a significant impact on all aspects of psychological symptom burden, with patients with low income being highly burdened (partial η² = .01, p = .023). The highest mean difference was found for depressive symptoms (MD = 0.13, CI = [0.07; 0.19], p < .001). The pandemic had no further influence on psychological distress Conclusions: Although the pandemic is a major stressor in many respects, poverty may be the more important risk factor for psychological symptom burden in cancer outpatients, outweighing the impact of the pandemic. (AU)

Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer.

Based upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death protein 1 monoclonal antibody, known to cause immune-related adverse events (irAEs) in a significant subset of patients. Real-world data on incidence, type and treatment strategies of irAEs in the setting of eTNBC treatment are sparse. In this multicenterretrospective analysis, we characterized real-world incidence of irAEs and treatment outcomes such as pathological complete response (pCR) from the combination of pembrolizumab and chemotherapy as neoadjuvant treatment for eTNBC. We found a rate of irAEs of all grades of 63.9% and of 20% for irAEs of grade 3 or higher. In the overall population, a pCR rate of 57.1% was observed. The emergence of irAEs correlated significantly with pCR (72.2% versus 30.8%; p =.03). Discontinuation of neoadjuvant chemotherapy before week 12 correlated significantly with a lower pCR rate. To our knowledge, this is the first study evaluating the real-world efficacy and safety of a neoadjuvant combination of chemotherapy and pembrolizumab in eTNBC, demonstrating a significant correlation between irAEs and pCR. Early discontinuation of neoadjuvant therapy due to AEs resulted in a lower pCR rate.

Differential immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel in breast cancer patients.

BACKGROUND: Epirubicin/cyclophosphamide (EC) and docetaxel (D) are commonly used in a sequential regimen in the neoadjuvant treatment of early, high-risk or locally advanced breast cancer (BC). Novel approaches to increase the response rate combine this treatment with immunotherapies such as PD-1 inhibition. However, the expected stimulatory effect on lymphocytes may depend on the chemotherapy backbone. Therefore, we separately compared the immunomodulatory effects of EC and D in the setting of a randomized clinical trial. METHODS: Tumor and blood samples of 154 patients from the ABCSG-34 trial were available (76 patients received four cycles of EC followed by four cycles of D; 78 patients get the reverse treatment sequence). Tumor-infiltrating lymphocytes, circulating lymphocytes and 14 soluble immune mediators were determined at baseline and at drug change. Furthermore, six BC cell lines were treated with E, C or D and co-cultured with immune cells. RESULTS: Initial treatment with four cycles of EC reduced circulating B and T cells by 94% and 45%, respectively. In contrast, no comparable effects on lymphocytes were observed in patients treated with initial four cycles of D. Most immune mediators decreased under EC whereas D-treatment resulted in elevated levels of CXCL10, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR). Accordingly, only the exposure of BC cell lines to D induced similar increases as compared to E. While treatment of BC cells with E was associated with cell shrinkage and apoptosis, D induced cell swelling and accumulation of cells in G2 phase. CONCLUSION: The deleterious effect of EC on lymphocytes indicates strong immunosuppressive properties of this combination therapy. D, in contrast, has no effect on lymphocytes, but triggers the secretion of stimulatory proteins in vivo and in vitro, indicating a supportive effect on the immune system. Underlying differences in the induced cell death might be causal. These divergent immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel should be considered when planning future combinations with immunotherapies in breast cancer.

Update Breast Cancer 2023 Part 1 - Early Stage Breast Cancer.

With abemaciclib (monarchE study) and olaparib (OlympiA study) gaining approval in the adjuvant treatment setting, a significant change in the standard of care for patients with early stage breast cancer has been established for some time now. Accordingly, some diverse developments are slowly being transferred from the metastatic to the adjuvant treatment setting. Recently, there have also been positive reports of the NATALEE study. Other clinical studies are currently investigating substances that are already established in the metastatic setting. These include, for example, the DESTINY Breast05 study with trastuzumab deruxtecan and the SASCIA study with sacituzumab govitecan. In this review paper, we summarize and place in context the latest developments over the past months.

Update Breast Cancer 2023 Part 2 - Advanced-Stage Breast Cancer.

In recent years, a number of new therapies have led to advances in the treatment of patients with advanced breast carcinoma. These substances are mainly CDK4/6 inhibitors and other substances that can overcome endocrine resistance, oral selective estrogen receptor degraders, antibody drug conjugates (ADCs), and PARP inhibitors. This review summarizes and evaluates the latest study results that have been published in recent months. This includes the overall survival data of the Destiny-Breast03 study, the first analysis of the CAPItello-291 study, the comparison of CDK4/6 inhibitor treatment with chemotherapy in the first line of therapy (RIGHT Choice study), the first analysis of the Destiny-Breast02 study in the treatment setting after T-DM1 treatment, and the first analysis of the Serena-2 study. Most of these studies have the potential to significantly change the therapeutic landscape for patients with advanced breast carcinoma and show that the continued rapid development of new therapies is always producing new results.

The impact of COVID-19 and socioeconomic status on psychological distress in cancer patients.

Objective: We aimed to investigate the impact of the COVID-19 pandemic on psychological symptom burden against the socioeconomic background of cancer patients using data from routine assessments before and during the pandemic. Method: In this cross-sectional study, standardised assessment instruments were applied in N = 1,329 patients to screen for symptoms of anxiety, depression, post-traumatic stress, and fatigue from 2018 to 2022. Two MANOVAs with post-hoc tests were computed. First, only time was included as predictor to examine the isolated impact of the pandemic. Second, income level and education level were included as further predictors to additionally test the predictive power of socioeconomic factors. Results: In the final model, only income had a significant impact on all aspects of psychological symptom burden, with patients with low income being highly burdened (partial η² = .01, p = .023). The highest mean difference was found for depressive symptoms (MD = 0.13, CI = [0.07; 0.19], p < .001). The pandemic had no further influence on psychological distress. Conclusions: Although the pandemic is a major stressor in many respects, poverty may be the more important risk factor for psychological symptom burden in cancer outpatients, outweighing the impact of the pandemic.

Update Breast Cancer 2023 Part 3 - Expert Opinions of Early Stage Breast Cancer Therapies.

The St. Gallen (SG) International Breast Cancer Conference is held every two years, previously in St. Gallen and now in Vienna. This year (2023) marks the eighteenth edition of this conference, which focuses on the treatment of patients with early-stage breast carcinoma. A panel discussion will be held at the end of this four-day event, during which a panel of experts will give their opinions on current controversial issues relating to the treatment of early-stage breast cancer patients. To this end, questions are generally formulated in such a way that clinically realistic cases are presented - often including poignant hypothetical modifications. This review reports on the outcome of these discussions and summarises the data associated with individual questions raised.

Updated Austrian treatment algorithm for metastatic triple-negative breast cancer.

Approximately 15% of newly diagnosed breast cancer patients have neither hormone receptors expression nor HER2 overexpression and/or HER2/neu gene amplification. This subtype of breast cancer is known as Triple Negative Breast Cancer (TNBC), and carries a significantly elevated risk of local and distant recurrence. In comparison with other breast cancer subtypes, there is a higher rate of visceral and brain metastases. The majority of metastases of TNBC are diagnosed within three years after initial breast cancer diagnosis. While there have been major advances in hormone-receptor- positive and in human epidermal growth factor receptor 2 (HER2)-positive disease over the past two decades, only limited improvements in outcomes for patients with triple negative breast cancer (TNBC) have been observed. A group of Austrian breast cancer specialists therefore convened an expert meeting to establish a comprehensive clinical risk-benefit profile of available mTNBC therapies and discuss the role sacituzumab govitecan may play in the treatment algorithm of the triple-negative breast cancer patients.

Risk as a pattern over time: Delineation of time-dependent risk factors in biological, psychological, and social variables in cancer patients.

BACKGROUND: Survival in cancer patients is associated with a multitude of biological, social, and psychological factors. Although it is well established that all these factors add to overall mortality, it is not well understood how the predictive power of these parameters changes in a comprehensive model and over time. METHODS: Patients who attended the authors' outpatient clinic were invited to participate. The authors followed 5180 mixed cancer patients (51.1% female; mean age, 59.1 years [SD = 13.8]) for up to 16 years and analyzed biological (age, sex, cancer site, anemia), psychological (anxiety, depression), and social variables (marital status, education, employment status) potentially predicting overall survival in a Cox proportional hazards model. RESULTS: The median survival time for the entire sample was 4.3 years (95% confidence interval, 4.0-4.7). The overall survival probabilities for 1 and 10 years were 76.8% and 38.0%, respectively. Following an empirical approach, the authors split the time interval into five periods: acute, subacute, short-term, medium-term, and long-term. A complex pattern of variables predicted overall survival differently in the five periods. Biological parameters were important throughout most of the time, social parameters were either time-independent predictors or tended to be more important in the longer term. Of the psychological parameters, only depression was a significant predictor and lost its predictive power in the long-term. CONCLUSIONS: The findings of this study allow the development of comprehensive patient-specific models of risk and resilience factors addressing biopsychosocial needs of cancer patients, paving the way for a personalized treatment plan that goes beyond biomedical cancer care.

Dexamethasone-sparing regimens with NEPA (netupitant/palonosetron) for the prevention of chemotherapy-induced nausea and vomiting in older patients (>65 years) fit for cisplatin: A sub-analysis from a phase 3 study.

INTRODUCTION: We recently demonstrated the non-inferiority of two dexamethasone (DEX)-sparing regimens with an oral fixed-combination of netupitant and palonosetron (NEPA) versus the guideline-recommended DEX use for cisplatin-induced nausea and vomiting. Since prevention of chemotherapy-induced nausea and vomiting is critical in older patients, we retrospectively evaluated the efficacy of the DEX-sparing regimens in this subset. MATERIALS AND METHODS: Chemo-naive patients aged >65 years treated with high-dose cisplatin (≥70 mg/m2) were eligible. Patients received NEPA and DEX on day 1 and were randomized to receive either (1) no further DEX (DEX1), (2) oral low-dose DEX (4 mg) on days 2-3 (DEX3), or (3) the guideline-recommended standard DEX (4 mg twice daily) on days 2-4 (DEX4). The primary efficacy endpoint of the parent study was complete response (CR; no vomiting and no use of rescue medication) during the overall phase (days 1-5). No significant nausea (NSN; none or mild nausea) and the proportion of patients reporting no impact on daily life (NIDL) which was evaluated by the Functional Living Index-Emesis questionnaire on day 6 (overall combined score > 108), were secondary endpoints. RESULTS: Among the 228 patients in the parent study, 107 were > 65 years. Similar CR rates [95% confidence intervals (CI)] were observed in patients over 65 years across treatment groups [DEX1: 75% (59.7-86.8%); DEX3: 80.6% (62.5-92.6%); DEX4: 75% (56.6-88.5%)] as well as versus the total study population. NSN rates were also similar in the older-patients across treatment groups (p = 0.480) but were higher compared with the total population. Similar rates of NIDL (95% CI) were reported in the older-patient subset across treatment groups [DEX1: 61.5% (44.6-76.6%); DEX3: 64.3% (44.1-81.4%); DEX4: 62.1% (42.3-79.3%); p = 1.0] during the overall phase, as well as versus total population. A similar proportion of older patients across treatment groups experienced DEX-related side effects. DISCUSSION: This analysis shows that older-patients who are fit for cisplatin benefit from a simplified regimen of NEPA plus single-dose DEX with neither loss in antiemetic efficacy nor the adverse impact on patient daily functioning. The study was registered on ClinicalTrials.gov (identifier NCT04201769) on 17/12/2019 (retrospectively registered).

Frequent Overexpression of HER3 in Brain Metastases from Breast and Lung Cancer.

PURPOSE: HER3 belongs to a family of receptor tyrosine kinases with oncogenic properties and is targeted by a variety of novel anticancer agents. There is a huge unmet medical need for systemic treatment options in patients with brain metastases (BM). Therefore, we aimed to investigate HER3 expression in BM of breast (BCa) and non-small cell lung cancer (NSCLC) as the basis for future clinical trial design. EXPERIMENTAL DESIGN: We analyzed 180 BM samples of breast cancer or NSCLC and 47 corresponding NSCLC extracranial tissue. IHC was performed to evaluate protein expression of HER3, and immune cells based on CD3, CD8, and CD68. To identify dysregulated pathways based on differential DNA methylation patterns, we used Infinium MethylationEPIC microarrays. RESULTS: A total of 99/132 (75.0%) of BCa-BM and 35/48 (72.9%) of NSCLC-BM presented with HER3 expression. Among breast cancer, HER2-positive and HER2-low BM showed significantly higher rates of HER3 coexpression than HER2-negative BM (87.1%/85.7% vs. 61.0%, P = 0.004). Among NSCLC, HER3 was more abundantly expressed in BM than in matched extracranial samples (72.9% vs. 41.3%, P = 0.003). No correlation of HER3 expression and intratumoral immune cell density was observed. HER3 expression did not correlate with overall survival from BM diagnosis. Methylation signatures differed according to HER3 status in BCa-BM samples. Pathway analysis revealed subtype-specific differences, such as TrkB and Wnt signaling pathways dysregulated in HER2-positive and triple-negative breast cancer BM, respectively. CONCLUSIONS: HER3 is highly abundant in BM of breast cancer and NSCLC. Given the promising results of antibody-drug conjugates in extracranial disease, BM-specific trials that target HER3 are warranted. See related commentary by Kabraji and Lin, p. 2961.

Understanding the activity of antibody-drug conjugates in primary and secondary brain tumours.

Antibody-drug conjugates (ADCs), a class of targeted cancer therapeutics combining monoclonal antibodies with a cytotoxic payload via a chemical linker, have already been approved for the treatment of several cancer types, with extensive clinical development of novel constructs ongoing. Primary and secondary brain tumours are associated with high mortality and morbidity, necessitating novel treatment approaches. Pharmacotherapy of brain tumours can be limited by restricted drug delivery across the blood-brain or blood-tumour barrier, although data from phase II studies of the HER2-targeted ADC trastuzumab deruxtecan indicate clinically relevant intracranial activity in patients with brain metastases from HER2+ breast cancer. However, depatuxizumab mafodotin, an ADC targeting wild-type EGFR and EGFR variant III, did not provide a definitive overall survival benefit in patients with newly diagnosed or recurrent EGFR-amplified glioblastoma in phase II and III trials, despite objective radiological responses in some patients. In this Review, we summarize the available data on the central nervous system activity of ADCs from trials involving patients with primary and secondary brain tumours and discuss their clinical implications. Furthermore, we explore pharmacological determinants of intracranial activity and discuss the optimal design of clinical trials to facilitate development of ADCs for the treatment of gliomas and brain metastases.

Epidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases: A systematic literature review.

BACKGROUND: There is an increasing need for developing effective therapies for managing intracranial disease in patients with human epidermal growth factor receptor 2-positive (HER2 +) metastatic breast cancer and brain metastases (BM), as this population is growing and has historically been excluded from large clinical trials. In this systematic literature review, we aimed to provide a comprehensive overview of the epidemiology, unmet needs, and global treatment landscape for patients with HER2 + metastatic breast cancer and BM, with a particular focus on heterogeneity across clinical trial designs in this setting. METHODS: We conducted literature searches of PubMed and select congress websites up to March 2022 and filtered for publications with a significant focus on epidemiology, unmet needs, or treatment outcomes in patients with HER2 + metastatic breast cancer and BM. RESULTS: Key clinical trials of HER2-targeting treatments for HER2 + metastatic breast cancer had varying eligibility criteria relating to BM, with only two trials-HER2CLIMB and DEBBRAH-including patients with both active and stable BM. We also observed variance across assessed central nervous system (CNS)-focused endpoints (CNS objective response rate vs CNS progression-free survival vs time to CNS progression) and robustness of statistical analysis (prespecified vs exploratory). CONCLUSIONS: There is an unmet need for standardization of clinical trial design for patients with HER2 + metastatic breast cancer and BM, to aid the interpretation of the global treatment landscape and ensure patients with all types of BM can access effective treatments.

Comparison of RNA Marker Panels for Circulating Tumor Cells and Evaluation of Their Prognostic Relevance in Breast Cancer.

Liquid biopsy is a promising tool for therapy monitoring of cancer patients, but a need for further research in this field exists in order to improve sensitivity, specificity, standardization and minimize costs. In our present study, we evaluated two panels of transcripts related with the presence of circulating tumor cells (CTCs) (Panel 1: CK19, EpCAM, SCGB2A2 and Panel 2: EMP2, SLC6A8, HJURP, MAL2, PPIC and CCNE2) in two cohorts of breast cancer patients (metastatic and early). A blood cell fraction possibly containing CTCs was isolated with density gradient centrifugation, followed by RNA isolation and qPCR using TaqMan® or RT-qPCR using hybridization probes. The positivity rates of the investigated panels were similar, albeit higher in metastatic (69.4% Panel 1, 75.0% Panel 2; total 86.1%) compared to early (18.9% Panel 1, 23.3% Panel 2; total 31.1%) breast cancer patients. CK19, SCGB2A2, EMP2, HJURP, MAL2, and CCNE2 individually correlated with shorter overall survival in the metastatic patient cohort. The findings highlight the additional value of Panel 2 markers, which are in contrast to CK19 and EpCAM not solely linked to an epithelial phenotype.

PERFORM: a non-interventional study assessing the patients' treatment starting with 1L palbociclib in HR+/HER2- ABC.

The prospective, non-interventional PERFORM study describes and analyzes the effectiveness of palbociclib in combination with endocrine therapy (aromatase inhibitor or fulvestrant) as first-line treatment for patients with locally advanced or metastatic HR+/HER2- breast cancer in the real-world setting in Germany and Austria. PERFORM will reflect current patient characteristics and routine treatment patterns including treatment sequences and time to subsequent (chemo)therapy. Besides, second-line treatment effectiveness and patient-relevant end points such as longitudinal patient-reported outcome measurements beyond disease progression will be analyzed. Accounting for the heterogenous real-world patient population, data on clinicopathologic subgroups underrepresented in clinical trials such as elderly or male will be analyzed. Taken together, PERFORM will close knowledge gaps from clinical trials in real world.

Palbociclib in combination with endocrine therapy is the standard first-line treatment for patients with advanced HR+/HER2- breast cancer. Data from clinical trials have shown high response rates and good tolerability. To support these data and close potential knowledge gaps, we conduct the multicenter, observational PERFORM study to evaluate the effectiveness and patient-reported outcomes in patients with advanced HR+/HER2- breast cancer treated with endocrine-based palbociclib therapy in routine clinical practice in Germany. Clinical Trial Registration: NCT04767594 (ClinicalTrials.gov) Sponsor: Pfizer Pharma GmbH, Linkstraße 10, D-10785 Berlin, Germany.

Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).

Atezolizumab plus nab-paclitaxel for unresectable, locally advanced or metastatic breast cancer: real-world results from a single academic center in Austria.

PURPOSE: IMpassion130 led to the approval of atezolizumab plus nab-paclitaxel as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative, PD-L1 immune-cell positive breast cancer (BC) by the European Medicines Agency (EMA). The objective of the present study was to investigate the implementation, safety and efficacy of this combination in the initial phase after approval. METHODS: A retrospective data analysis including all BC patients who received atezolizumab and nab-paclitaxel between 1.1.2019 and 31.10.2020 at the Department of Obstetrics and Gynecology and the Department of Medicine 1, respectively, at the Medical University of Vienna, Austria, was performed. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Maier product-limit method. Owing to the retrospective nature of this study, all statistics must be considered exploratory. RESULTS: In total 20 patients were included in the study. Median follow-up was 7.1 months (IQR 5.2-9.1). Median PFS was 3.0 months (SE = .24; 95% CI [2.5; 3.5]). Median OS was 8.94 months (SE = 2.34, 95%CI [4.35; 13.53]). No new safety signals were observed. CONCLUSION: The present study showed a considerably shorter PFS (3.0 vs. 7.5 months) and OS (8.94 vs. 25.0 months) than IMpassion130 putatively owing to the use of atezolizumab in later treatment lines, more aggressive tumors and a study population with higher morbidity compared to the pivotal trial.