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Simple Summary: Hepatocellular carcinoma is the most common type of liver cancer and is often seen in people with chronic liver diseases. For patients with hepatocellular carcinoma who cannot receive surgery, other treatments include atezolizumab plus bevacizumab, sorafenib, or lenvatinib. We compared the length of life among 1874 United States veterans who received these therapies, both in the overall population of patients and in groups by race/ethnicity. The results showed that the risk of death was 30% lower with atezolizumab plus bevacizumab compared with sorafenib, and 26% lower compared with lenvatinib. These trends were consistent across White, Black, and Hispanic patients. Thus, patients who received atezolizumab plus bevacizumab had improved survival outcomes compared with those treated with sorafenib or lenvatinib, regardless of race or ethnicity. Background/Objectives: This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. Methods: In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017–31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan–Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. Results: Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank p < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both p < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. Conclusions: Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the real-world efficacy and safety of combining pembrolizumab, a novel immunotherapy agent, with chemotherapy in early-stage triple-negative breast cancer treatment. We specifically aimed to validate clinical trial results in routine practice. A total of 108 Turkish patients receiving neoadjuvant therapy were examined. The combined regimen demonstrated high efficacy, with 64% of patients achieving pathological complete response, and exhibited generally favorable safety profiles with predominantly mild adverse events. These findings support the use of this combination as a standard treatment for this aggressive breast cancer subtype. However, the results underscore the need for further research to identify optimal patient selection criteria, which can inform oncologists' decision-making and potentially enhance outcomes for patients with triple-negative breast cancer. Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in Türkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1–2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab–chemotherapy in early-stage TNBC, complementing evidence from randomized trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Abemaciclib in combination with endocrine therapy is a standard first- or later-line of treatment for HR+/HER2− metastatic breast cancer (MBC). Real-world studies provide valuable addition to pivotal trials by including a heterogeneous patient population, particularly subgroups that are often underrepresented (e.g., elderly patients). This study retrospectively collected data on the efficacy and safety of abemaciclib in a real-world patient population. The safety and efficacy of the treatment were consistent with the pivotal studies, including in elderly patients. Comparable survival outcomes were observed between the first two lines of treatment. Additionally, metastatic disease survival was greatly prolonged, exceeding 5 years compared to historical data. The study provides further reassurance that dose reductions do not affect survival. The safety profile of abemaciclib was consistent with previous findings, and no new adverse events (AEs) were identified. Although abemaciclib was well tolerated in elderly patients, the careful monitoring and management of AEs is still warranted. (1) Background: Abemaciclib combined with endocrine therapy is a standard first- or later-line of treatment for HR+/HER2− metastatic breast cancer (MBC). The aim of this retrospective cohort study was to describe the outcomes of patients treated in a real-world setting, with particular focus on elderly patients. (2) Patients and methods: Patients treated with abemaciclib between November 2019 and February 2022 were included in the study. Data were collected from electronic medical records. The primary objective was to determine real-world progression-free survival (rwPFS), and secondary objectives included median overall survival (mOS) and safety. (3) Results: Analysis included 134 patients, with a median follow-up of 42 months. Median age was 62 years, with 29.9% aged 70+ years. A total of 51.5% of patients received abemaciclib in first-line, predominantly with aromatase inhibitor (68.1%). Median rwPFS was 21 in first-line and 20 months in the second-line, with no significant difference between treatment lines (HR 0.96; p = 0.88). Patients treated in the third- or later-line had a significantly shorter rwPFS, at 7 months (HR 1.48, p = 0.003). mOS was not reached in the first-line setting. For second- and third- or later-lines, mOS was 29 and 19 months, respectively. There was no significant difference in mOS between first- or second-line (HR 1.37, p = 0.36). In the 70+ group, median rwPFS was 15 months and mOS was 25 months with no significant difference compared to younger patients (rwPFS HR 1.1; p = 0.65; OS HR 1.4; p = 0.21). Most common adverse events (AEs) were diarrhoea (68.7%), anaemia (64.9%), and increased serum creatinine (63.4%). Grade 3/4 AEs were reported in 21.6% of patients. Dose reductions occurred in 30.6% of patients and were more frequent in patients 70+ (40%) compared to younger patients (28%); the difference was not significant (p = 0.22). At study cut-off, 64.9% of patients discontinued abemaciclib, primarily due to disease progression (73.5%). (4) Conclusions: Our study provides valuable insights into the effectiveness and safety of abemaciclib for the treatment of MBC. We observed comparable outcomes in terms of rwPFS and OS between the first two lines, suggesting consistent effectiveness across treatment lines. In addition, our findings suggest that older age (70+) does not significantly impact the effectiveness and tolerability of abemaciclib, although the careful monitoring and management of AEs are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Undifferentiated pleomorphic sarcomas (UPSs) represent 10–20% of all soft tissue sarcomas (STSs) and have quickly emerged as one of the more immune-sensitive types. There are few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and those with other high-grade pleomorphic STSs. This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center intended to describe the efficacy and toxicity of ICB in this particular group of patients. We find that our outcomes are comparable to those in the published literature and pose a question regarding the need to further evaluate the optimal sequencing of radiotherapy and prior lines of systemic therapy. Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. Methods: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Results: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Conclusions: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors. [ABSTRACT FROM AUTHOR]

Simple Summary: On rare occasions, a handful of innovative cancer drugs may successfully go through clinical trials and manage to obtain simultaneous regulatory approvals to treat a specific disease, providing hope for improved treatment outcomes. In the past few years, physicians in North America, Europe, and other countries with stronger economies have been able to use several of the recently approved drugs to treat a blood cancer called multiple myeloma, once older therapies have failed. This study looked at the treatment outcomes associated with the wave of newer drugs in patients diagnosed with multiple myeloma in Greece. The results showed that approximately three-quarters of patients who received one of the newer drugs after having progressed on front-line therapies remained in remission a year after initiating treatment. This finding was comparable to the results from previous studies in Greek patients who were diagnosed with relapsed or refractory multiple myeloma and had previously used other therapies. Newer methodologies are needed to assess the real-world comparative effectiveness of a "generation" of pharmaceutical innovation versus the prior standard of care. This chart review study aimed to first evaluate the cumulative clinical benefits of pharmaceutical innovation in everyday relapse/refractory multiple myeloma before analyzing findings in the context of respective real-world outcomes from the bortezomib/lenalidomide era. Study endpoints included the 52-week PFS rate in second and third line of therapy (LOT), mPFS-2 across the first and second LOT, the ORR, reasons for discontinuation, and the treatment duration per therapeutic algorithm. Data from 107 patients were collected. The median follow-up was 2.0 years. Of the subjects who met the selection criteria for the second LOT, 72.2% maintained the PFS at 52 weeks. In the third-line setting, the PFS rate at 52 weeks was 63.5%. The mPFS across the first and second, the second, and the third LOTs were 26, 17, and 15 months, respectively. The ORR was 76.1% in the second and 69.7% in the third LOT. After non-response or progression, the main reason for drug discontinuation was treatment intolerability. The second-line ORR and the 52-week PFS rate were similar to previous real-world findings from the bortezomib/lenalidomide era. The cumulative mPFS across the second and third LOTs was higher than the respective mPFS across the first and second LOTs. Despite its limitations, the methodology and findings from this study may be used in future clinical and economic evaluations across all hematological malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Clinical trials (CTs) may not always reflect real-world medical practice, particularly in non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients due to stringent recruitment criteria. Our objective was to assess exclusion rates, reasons, and survival outcomes for NTE NDMM patients in and out of CTs. Roughly 50% did not meet eligibility criteria, mainly due to comorbidities, poor ECOG-PS, or renal failure. CT participation correlated with higher overall response rates (ORRs), improved progression-free survival (PFS) and overall survival (OS), especially in recent years. A slight PFS extension associated with a substantial improvement in OS in CT patients suggested a selection bias. Excluded patients did not experience improved survival, with the median OS remaining unchanged from 2003 to 2017. These findings emphasize that CT participants may not fully represent the wider NDMM population in real-world clinical practice. It is essential to exercise caution when applying CT results to routine care settings, recognizing the limitations of generalization. The proportion of non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients excluded from clinical trials (CTs) and their prognosis is unknown. CT results may not be generalizable to real-world practice due to strict recruitment criteria. We analyzed causes of NTE-NDMM patient exclusion form CTs and their outcomes. A total of 211 NTE-NDMM patients were included. They were divided into three periods: 2003–2007, 2008–2012, and 2013–2017. Overall, 50% received non-trial treatment (NCT), while 50% participated in a CT (20% control group (CG) and 30% experimental group (EG)). Main causes for exclusion from CTs were comorbidities, ECOG > 2, and renal insufficiency. In the first two periods, the CR rate was similar regardless of treatment type, but in the last period, the EG group showed improved CR. Median PFS was similar in the first two periods, with a benefit seen only in the EG in the last period. The median OS was significantly longer in CT-included patients compared to NCT group in the last two periods. Conclusions: The presence of comorbidities and worsened ECOG were the main reasons for CT exclusion. Patients included in CTs had a longer OS than NCT. This OS benefit may be influenced by a selection bias, making it challenging to generalize CT results to real clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Enfortumab vedotin, a targeted therapy for advanced urothelial carcinoma, has shown efficacy, especially in those treated with platinum-based chemotherapy and immune-checkpoint inhibitors. The EV-301 phase III trial reported enhanced overall survival and response rates than conventional chemotherapy. However, its effectiveness in Japanese patients needs further real-world validation. Analyzing 6007 urothelial cancer patients treated with pembrolizumab, 563 subsequently received enfortumab vedotin, while 443 switched to docetaxel or paclitaxel. Results indicated the enfortumab vedotin group had an extended overall survival compared to the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). Conclusively, enfortumab vedotin offers Japanese patients better overall survival prospects after pembrolizumab treatment than docetaxel or paclitaxel. Background: Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. However, more data, especially from larger real-world studies, are needed to further assess its effectiveness in Japanese patients. Methods: A total of 6007 urothelial cancer patients inducted with pembrolizumab as a second-line treatment were analyzed. Among them, 563 patients received enfortumab vedotin after pembrolizumab, while 443 patients received docetaxel or paclitaxel after pembrolizumab, and all were included in the study for efficacy as a life prolonging agent. Results: The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). In multivariate analysis, enfortumab vedotin induction was the independent risk factor for overall survival (p = 0.013, HR: 0.70). There were no significant differences in cancer-specific survival. Conclusions: Enfortumab vedotin prolonged the overall survival for Japanese advanced or metastatic urothelial carcinoma patients compared to paclitaxel or docetaxel after pembrolizumab treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple treatment regimens are approved for relapsed/refractory multiple myeloma (RRMM), but evidence of their real-world use is limited. This study included 701 patients across 11 countries in Europe and Israel between March 2017 and March 2020, and examined the real-world use of carfilzomib in adults with RRMM who received at least one prior line of therapy. Here, we describe the results for 271 patients who received carfilzomib and dexamethasone (Kd). The overall response rates (ORR) with Kd treatment were high, both overall (68.8%) and by treatment line. In patients who are refractory to lenalidomide, the ORR of 59.9% is an encouraging outcome. In patients refractory to anti-CD38 treatment, the ORR was higher for those receiving Kd in earlier (66.7%) than later lines (fourth line or later, 49.1%). Our study demonstrates that Kd is used effectively, with an acceptable safety profile in routine clinical practice. This prospective, observational study examined the real-world use of carfilzomib across 11 European countries in adults with relapsed/refractory multiple myeloma (RRMM) who received at least one prior line of therapy. Carfilzomib and dexamethasone (Kd) use, effectiveness and safety were analyzed. In total, 271 patients received Kd among 701 adults enrolled. The median relative dose intensity of carfilzomib was 82.7% (20/56 mg/m2, twice weekly). The overall response rate (ORR) to Kd was 68.8% (95% confidence interval [CI], 62.7–74.5): 79.2% in second line (2L), 71.6% in third line (3L) and 63.1% in fourth line or later (4L+). The ORR was 59.9% (95% CI, 51.1–68.1) in the lenalidomide-refractory subgroup and 67.7% (95% CI, 48.6–83.3) in the not lenalidomide-refractory subgroup. In the anti-CD38 refractory subgroup, the ORR was 51.6% (95% CI, 38.6–64.5); ORRs were higher when Kd was received at 2L/3L (66.7%) than at 4L+ (49.1%). Overall, patients were treated for a median time of 7.7 months. One-fifth of patients reported treatment-related treatment-emergent adverse events (≥grade 3), with a safety profile consistent with previous clinical trials. This study demonstrated the real-world use, effectiveness and safety of Kd in patients with RRMM. Despite the increasing number of new therapeutic strategies to treat RRMM, Kd remains a safe and effective option, even for older, frail and lenalidomide- or anti-CD38 mAb-refractory patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma is one of the most common cancers in the world with increasing incidence. In advanced stages, according to the Barcelona Clinic Liver Cancer (BCLC) staging defined by number, size, vessel infiltration status, and patient's performance status, the therapy of choice is systemic therapy. For several years, the tyrosine kinase inhibitor sorafenib was the only therapeutic option. Atezolizumab and bevacizumab are administered as a combination therapy promoting PD-L1 inhibition and anti-VEGF activity, which yields synergistic effects against cancer. The IMBRAVE150 trial investigated the use of this combination therapy versus that of sorafenib and showed an increase in overall patient survival to nearly 20 months. In this work, we investigated the real-world efficacy and safety of this combination in different centers. The combination of atezolizumab and bevacizumab (A + B) is the new standard of care for the systemic first-line treatment of hepatocellular carcinoma (HCC). However, up to now there are only few data on the safety and efficacy of A + B in real life. We included patients with advanced HCC treated with A + B as first-line therapy at four cancer centers in Germany and Austria between December 2018 and August 2021. Demographics, overall survival (OS), and adverse events were assessed until 15 September 2021. We included 66 patients. Most patients had compensated cirrhosis (n = 34; 52%), while Child–Pugh class B cirrhosis was observed in 23 patients (35%), and class C cirrhosis in 5 patients (8%). The best responses included a complete response (CR) in 7 patients (11%), a partial response (PR) in 12 patients (18%), stable disease (SD) in 22 patients (33%), and progressive disease in 11 patients (17%). The median progression-free (PFS) survival was 6.5 months, while the median overall survival (OS) was not reached in this cohort (6-month OS: 69%, 12-month OS: 60%, 18-month OS: 58%). Patients with viral hepatitis seemed to have a better prognosis than patients with HCC of non-viral etiology. The real-world PFS and OS were comparable to those of the pivotal IMBRAVE trial, despite including patients with worse liver function in this study. We conclude that A + B is also highly effective in a real-life setting, with manageable toxicity, especially in patients with compensated liver disease. In patients with compromised liver function (Child B and C), the treatment showed low efficacy and, therefore, it should be well considered before administration to these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers of the biliary tract are rare but severe with high mortality rates. Randomised controlled trials suggest that chemotherapies such as gemcitabine and oxaliplatin (GemOx) may relieve symptoms and prolong life, but less is known on the efficacy and safety of such regimens in real life. The current paper assessed the real-world outcome of GemOx in all patients with advanced biliary tract cancer treated at any cancer centre in the South East Region of Sweden over a period of nine years. The median overall survival was nine months and time to disease progression five months. Prognostic factors such as performance status and gall bladder (rather than bile duct) localisation of the primary tumour were identified. Most patients received a lower dose of oxaliplatin than proposed by previous studies, which seemed feasible as few patients had severe adverse events. This study supports further use of GemOx as standard of care. Background: Gemcitabine and oxaliplatin (GemOx) is a standard combination regimen in advanced biliary tract cancer (BTC). There is limited evidence on its efficacy and safety in real life. Methods: A retrospective multicentre cohort study in the South East Region of Sweden, covering nine years (2011–2020) and three hospitals where GemOx was treatment of choice, was designed. Clinicopathological prognostic parameters were explored. Results: One hundred and twenty-one patients with advanced BTC were identified. Median overall and progression-free survival (OS and PFS) were 8.9 (95% CI = 7.2–10.6) and 5.3 (95% CI = 3.8–6.7) months. Performance status according to Eastern Cooperative Oncology Group (PS according to ECOG) 1–2 and primary gallbladder carcinoma were independent predictors for poor OS. PS and derived neutrophil/lymphocyte ratio were predictive for PFS. The most common severe type of myelosuppresion was grade 3 neutropenia that was recorded in 8%. Fifty-three (43.8%) experienced at least one episode of unplanned hospitalisation. One hundred and seventeen (97%) received oxaliplatin with lower dosage than was utilized in previous phase III trials (80–85 vs. 100 mg/m2) and a majority received further dose reductions of oxaliplatin and/or gemcitabine. Conclusion: The outcome of GemOx in advanced BTC appears comparable in controlled trials and real-world contexts. A lower dose of oxaliplatin seems more tolerable without compromising the outcome. [ABSTRACT FROM AUTHOR]