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BACKGROUND: This study evaluated tislelizumab combined with low-dose bevacizumab in recurrent glioblastoma (rGBM), assessing efficacy, safety, and mechanisms of immune escape. METHODS: This randomized phase 2 trial divided patients into treatment arms with distinct strategies. Longitudinal tumor in situ fluid (TISF) samples were collected for molecular analysis to monitor genome evolution. Immunohistochemical markers in paired primary and recurrent tumor specimens were analyzed to assess therapy-induced immune resistance. RESULTS: A total of 109 patients were included, with 59 in the control group and 50 in the experimental group. No grade 4 adverse events or treatment discontinuations occurred in the experimental group. The experimental group demonstrated a median overall survival of 13.3 months, compared to 6.6 months in the control group. The objective response rate and disease control rate were 32.6% and 79.1%, respectively. Post-treatment TISF analysis revealed a 68.4% reduction in detectable genomic alterations. Immunophenotypic analysis of paired tumor samples showed increased infiltration of CD163+ macrophages and elevated GDF-15 expression in recurrent tumors. CONCLUSION: This study shows that combining tislelizumab and low-dose bevacizumab improves survival in rGBM patients with good safety and tolerability. Dynamic changes in TISF-based molecular markers reflect genomic evolution and predict prognosis. Increased CD163+ cell infiltration in recurrent tumors may activate M2 macrophages, promoting tumor growth and immune evasion. Elevated GDF-15 levels may further suppress antitumor immunity, facilitating immune escape.

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BACKGROUND/AIM: Bevacizumab (Bev) often induces hypertension and proteinuria. Optimal antihypertensive management in this setting remains unclear, and studies comparing angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) are limited. The objective of this study was to compare the effects of the ARB azilsartan and the CCB amlodipine on hypertension and proteinuria. PATIENTS AND METHODS: Patients with demonstrated systolic/diastolic blood pressure (SBP/DBP) ≥140/90 mmHg during Bev therapy for colorectal cancer were randomly assigned 1:1 to either the azilsartan group or the amlodipine group and were followed up for 18 weeks. The primary outcome was urinary protein-to-creatinine ratio (UPCR). Secondary outcomes included BP changes and achievement of target BP (<140/90 mmHg). After week six, the attending physician adjusted the antihypertensive medication as needed. RESULTS: Thirty patients were enrolled, and 26 (13 per group) completed 18 weeks of treatment. Mean baseline SBP was 156.8±9.2 mmHg in the azilsartan group and 158.0±9.4 mmHg in the amlodipine group. At week six, SBP decreased to 151.4±21.9 mmHg and 144.5±15.2 mmHg, respectively, with a significant reduction in the amlodipine group. At week 18, SBP was 136.5±12.9 mmHg vs. 138.7±14.9 mmHg. Target BP was achieved in 23% of patients at week six and in 40-50% at week 18, with no difference between groups. No significant difference in UPCR was observed at any time point. Subgroup analysis revealed that patients with proteinuria consistently had higher BP. CONCLUSION: These findings emphasize that adequate BP control, rather than antihypertensive class, may be critical in managing Bev-induced proteinuria.

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BACKGROUND: Autoimmune encephalitis (AE) is increasingly recognized in clinical practice, yet drug-related encephalitic syndromes remain a diagnostic challenge. Immune checkpoint inhibitors (ICIs) are well-established triggers, whereas vascular endothelial growth factor (VEGF) inhibitors such as Bevacizumab are only rarely implicated, with evidence confined to case reports. Awareness of this association is essential as targeted therapies gain prominence in metastatic cancer care. CASE PRESENTATION: We describe a 58-year-old woman with hypothyroidism and advanced ovarian carcinoma, who had previously undergone surgery and adjuvant chemotherapy in 2022 and metastasectomy for bowel involvement in 2024. She was in remission under Bevacizumab-chemotherapy combination therapy when, following reoperation for peritoneal adhesions in February 2025, she developed two episodes of transient loss of consciousness. During the attacks, fluctuating blood pressure, visual phenomena, and transient foreign-language speech were observed. MRI initially revealed left occipital leptomeningeal enhancement, and EEG showed lateralized epileptiform discharges and non-convulsive status epilepticus was considered. Although initial events were interpreted as seizure-related changes, follow-up imaging on day 15 revealed persistent abnormalities with new cortical and thalamic FLAIR hyperintensities. Neurological examination demonstrated drowsy consciousness, right homonymous hemianopia, motor aphasia, dystonic posturing of the right hand, and sensory integration deficits. Cerebrospinal fluid cytology, paraneoplastic, and autoimmune antibody panels were negative. Pulse intravenous methylprednisolone was initiated, leading to significant clinical improvement and partial radiologic regression, although word-finding difficulties persisted at last follow-up. CONCLUSION: This case illustrates an atypical, steroid-responsive encephalitic syndrome temporally associated with Bevacizumab. Unlike the well-characterized bilateral parieto-occipital patterns of PRES, our patient demonstrated unilateral leptomeningeal and cortical-thalamic involvement. The case underscores the importance of repeated neuroimaging, systematic exclusion of alternative etiologies, and timely immunotherapy in suspected drug-related encephalitis. Accumulation of further cases will be essential to clarify incidence, mechanisms, and optimal management of Bevacizumab-associated encephalitis.

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BACKGROUND & AIMS: Despite the advances in systemic therapy for unresectable hepatocellular carcinoma (HCC), patients with Child-Pugh class B (CP-B) liver function face a significant unmet need. This study evaluated the efficacy and safety of atezolizumab plus bevacizumab (Atez/Bev) in patients with unresectable HCC and CP-B. METHODS: This retrospective study included 796 patients who received Atez/Bev between October 2020 and July 2024 from 10 institutions in Japan. The median observation period was 14.6 months. The liver function was assessed using the CP classification and modified ALBI (mALBI) grade. The progression-free survival (PFS), overall survival (OS) and median survival time (MST) were evaluated. RESULTS: Patients with CP-B had significantly shorter PFS and OS than those with CP-A (median PFS, 4.6 months vs. 7.0 months; MST, 10.3 months vs. 23.2 months) (PFS, p = 0.009; OS, p < 0.001). Although CP-B was associated with a higher incidence of bleeding-related events, the discontinuation rate due to adverse events did not differ from that of CP-A. As a factor for stratifying CP-B outcomes, significant differences in the PFS, OS and response rate were observed between mALBI grades ≤ 2b and 3 (PFS, p = 0.004; OS, p = 0.024; response rate, p = 0.001). In multivariate analysis, the mALBI grade (hazard ratio [95% CI]: 2.388 [1.186-4.810]; p = 0.014) was extracted as a factor contributing to OS in patients with CP-B. CONCLUSION: Atez/Bev therapy demonstrated efficacy and safety in patients with CP-B, especially when hepatic reserve is maintained within mALBI grade 2b.

This study shows that atezolizumab plus bevacizumab can be a safe and effective treatment option for patients with unresectable liver cancer and moderate liver impairment (Child­Pugh class B), particularly those with preserved liver function up to mALBI grade 2b. These findings may help expand treatment options for a population with limited existing choices.

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BACKGROUND: Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) rescues retinal vasculatures and prevents disease progression in patients with neovascular Age-Related Macular Degeneration (nAMD). However, systemic anti-VEGF may increase the risk of thromboembolic related complications including stroke and TIA. This study aims to explore the association between stroke and intravitreal anti-VEGF agents; ranibizumab, aflibercept and bevacizumab. METHODS: This nationwide, population- registry-based case-control study used registered data 2007-2019. Data from the Swedish Stroke Registry (Riksstroke) and the Swedish Macula Register (SMR) were cross-linked to identify nAMD patients who developed stroke/TIA within 90 days after intravitreal anti-VEGF injection. Each stroke case was matched with three controls from Riksstroke with stroke/TIA but no anti-VEGF treatment. RESULTS: A total of 33 585 patients with nAMD underwent intravitreal anti-VEGF agent injections. A stroke occurred in 1693 patients of this group, and 936 of them within 90 days of treatment. Compared with nonuse, intravitreal anti-VEGF agent use was associated with an increased risk of stroke within 90 days of anti-VEGF treatment in 2.9% of the nAMD-patients [Risk Ratio (RR) 1.27, 95% confidence interval (CI) 1.22; 1.33] compared to non-users. The RR within 30, 31-60 and 61-90 days were 1.36 (1.15; 1.66), 1.40 (1.09; 1.79) and 0.58 (0.52; 0.65), respectively. CONCLUSIONS: Even though the risk is small, intravitreal injections with anti-VEGF agents for the treatment of nAMD are associated with an increased risk of stroke/TIA. The risk seems to be higher within 60 days of last injection. An assessment of high-risk populations and risk-benefit weighting is necessary before intravitreal anti-VEGF injections are considered.

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BACKGROUND: Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespectively of sex. However, differences relating to safety and efficacy in the treatment of mCRC between male and female patients are of growing interest. METHODS: The randomized FIRE-3 study compared first-line treatment with folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) plus cetuximab to FOLFIRI plus bevacizumab in patients with RAS wildtype (RAS WT) mCRC. The present analysis focusses on the impact of sex and primary tumor (PT) sidedness on outcome parameters. RESULTS: Of 352 patients with RAS WT tumors, 249 (71 %) were male and 103 (29 %) female. In male patients with left-sided RAS/BRAF WT tumors, a significant benefit from cetuximab was noted with regard to ORR (OR 1.15; P = 0.035) and OS (0.66; P = 0.010), while in right-sided patients cetuximab improved ORR (OR 2.92) and had no significant effect on PFS or OS. In female patients with left-sided, RAS/BRAF WT PT, a comparable effect of cetuximab versus bevacizumab was observed with regard to ORR (OR 1.05; P > 0.999), while a numerical OS benefit was noted in the cetuximab-arm (HR 0.78; P = 0.385). By contrast, in female patients with right-sided PT, a clearly detrimental effect of cetuximab-based therapy was observed for ORR (OR 0.44; P = 0.617), PFS (HR 4.95; P = 0.005), and OS (HR 2.58; P = 0.080). In the bevacizumab arm, neutropenia grade ≥ 3 was more frequent in female versus male patients (30.6 % versus 18.3 %; P = 0.063). Otherwise, there was no significant difference of grade ≥ 3 adverse events between male and female patients. CONCLUSIONS: The exploratory analysis of FIRE-3 suggests that the efficacy of cetuximab combined with FOLFIRI in RAS wild-type mCRC is related to sex and primary tumor sidedness. The results support the inclusion of patient sex into the design of future trials.

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PURPOSE: To evaluate atezolizumab combined with bevacizumab and non-platinum-based chemotherapy for recurrent ovarian cancer. METHODS: The double-blind randomized phase III AGO-OVAR 2.29/ENGOT-ov34 trial (ClinicalTrials.gov identifier: NCT03353831) enrolled patients with first or second relapse of ovarian cancer ≤6 months after completing platinum-based chemotherapy (or third relapse regardless of treatment-free interval). PD-L1 status was tested centrally (VENTANA SP142 assay) in recent (<3 months) biopsies before random assignment. All patients received bevacizumab and investigator-selected chemotherapy (once weekly paclitaxel or pegylated liposomal doxorubicin) until disease progression or toxicity, plus either atezolizumab 840 mg or placebo once every 2 weeks until progression (maximum 2 years), randomly assigned 1:1, and stratified by number of previous lines, planned chemotherapy, previous bevacizumab, and PD-L1 status. Primary end points were overall survival (OS) and progression-free survival (PFS) in the intention-to-treat population. RESULTS: Among 574 patients randomly assigned between September 2018 and July 2022, 72% were bevacizumab-pretreated, 36% had received three previous treatment lines, 26% had PD-L1-positive tumors, and 54% received paclitaxel with study therapy. After 418 patients had died, the hazard ratio for OS was 0.83 (95% CI, 0.68 to 1.01; P = .06; median 14.2 months with atezolizumab and 13.0 months with placebo) and the hazard ratio for PFS was 0.87 (95% CI, 0.73 to 1.04; P = .12; median 6.4 v 6.7 months, respectively). OS hazard ratios were similar regardless of PD-L1 status. Grade ≥3 adverse events occurred in 72% of atezolizumab-treated and 69% of placebo patients. CONCLUSION: Combining atezolizumab with bevacizumab and chemotherapy did not significantly improve OS or PFS in patients with recurrent ovarian cancer ineligible for platinum. The safety profile was as expected from previous experience with these drugs.

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BACKGROUND/AIM: Bevacizumab (BV) is used in combination with paclitaxel to treat human epidermal growth factor receptor 2-negative advanced breast cancer. However, BV frequently causes hypertension. Because patients with advanced breast cancer already have an elevated cardiovascular risk, we investigated clinical factors associated with BV-induced severe hypertension in a real-world setting. PATIENTS AND METHODS: Patients with advanced breast cancer receiving BV with paclitaxel (n=67) were retrospectively evaluated. The primary endpoint was determination of factors for the occurrence of grade ≥3 severe hypertension, considering clinical significance. We also assessed the time to symptom onset and variation in blood pressure after treatment between specific patient groups. RESULTS: Hypertension occurred in 73.1% of the patients, with grades 2 and 3 severity in 20.9% and 52.2%, respectively. Multivariate logistic regression analysis suggested that pre-existing hypertension at baseline was an independent risk factor for grade ≥3 hypertension (adjusted hazard ratio=3.12; 95% confidence interval=1.30-7.87; p=0.01), resulting in similar results in a sensitive analysis. Additionally, median time to symptom onset was 70 days (range=56-119 days) in patients with pre-existing hypertension and 175 days (147 days-not available) in patients without pre-existing hypertension (p=0.004). No significant difference was noted in the range of fluctuations in systolic and diastolic blood pressure during treatment between patients with and without pre-existing hypertension. CONCLUSION: Pre-existing hypertension is a risk factor for BV-induced severe hypertension in patients with breast cancer.

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Antiangiogenic therapy with bevacizumab improves outcomes in ovarian cancer but induces hypertension, leading to major adverse cardiovascular events (MACE). While calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEi) are recommended for managing bevacizumab-associated hypertension, their impacts on cancer progression and cardiovascular outcomes are unclear. This study compared the effects of CCBs and ACEi on progression-free survival (PFS) in ovarian cancer patients treated with adjuvant bevacizumab. The incidence of MACE and overall survival (OS) were also evaluated. We conducted an emulated clinical trial using data from January 1, 2011, to January 1, 2021, from the French National Health Data System (SNDS), covering 98.8% of the French population. Patients with FIGO stage III to IV ovarian cancer who underwent cytoreductive surgery and adjuvant chemotherapy with bevacizumab, treated with CCBs or ACEi monotherapy within 6 months after surgery, were included. Out of 4,165 patients treated with bevacizumab, 454 met inclusion criteria for the main analysis: 273 in the CCBs group and 181 in the ACEi group. CCBs use was associated with a longer median PFS compared to ACEi (21.8 vs. 18.2 months) and a higher 3-year PFS rate (difference of 8.2 percentage points, 95% CI: 2.0%; 14.8%). No significant difference in OS was observed between groups. Cardiovascular complications were more frequent with CCBs compared to ACEi, particularly congestive heart failure (difference in 3-year incidence of MACE: -4.5 percentage points; 95% CI: -8.2%; -1.1%). These findings emphasize the need for a balanced approach to managing hypertension in cancer patients, considering both oncologic and cardiologic outcomes.

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BACKGROUND AND AIM: Data on sequential immune checkpoint inhibitor (ICI) retreatment following initial atezolizumab plus bevacizumab (Atez + Bev) are limited. This study aimed to evaluate the efficacy and safety of sequential ICI retreatment in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Of 835 patients with uHCC treated with Atez + Bev, 75 who underwent ICI retreatment after initial Atez + Bev therapy were included in this multicenter retrospective study that assessed the efficacy and safety of ICIs. RESULTS: The participants received one of three sequential retreatments with ICI regimens: durvalumab plus tremelimumab (n = 58), retreatment with Atez + Bev (n = 15), and durvalumab monotherapy (n = 2). The objective response rates (ORRs)/disease control rates (DCRs) for the initial Atez + Bev and sequential ICI retreatment were 34.7%/89.3% and 18.7%/54.7%, respectively. No significant differences in antitumor response were observed among the three ICI retreatment regimens. Patients who achieved a good antitumor response (≥ stable disease) following retreatment showed a significantly longer overall survival. Multivariate analysis identified prior objective response to Atez + Bev as an independent predictor of disease control after retreatment (odds ratio: 3.79, p = 0.016). Immune-related adverse events (irAEs) requiring corticosteroids occurred in 26.7% of the patients during ICI retreatment, with enterocolitis and rash being the most common. The recurrence rate of irAEs was 15.4% in patients with previous steroid-requiring irAEs. CONCLUSIONS: Sequential ICI retreatment may be a viable therapeutic option for selected patients with uHCC, particularly those with a favorable response to prior Atez + Bev. Although less effective than first-line therapy, careful patient selection and monitoring ensure efficacy with acceptable safety.

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The purpose of this study was to determine the safety and feasibility of fluorescence molecular imaging using a commercially available system and intravenous injection of fluorescently labeled bevacizumab (bevacizumab-800CW) to visualize bevacizumab distribution in patients with neovascular age-related macular degeneration (nAMD)s. Methods: Twelve patients with active nAMD aged 60 y or older, who were either on anti-vascular endothelial growth factor (VEGF) therapy or were anti-VEGF therapy naïve, received an intravenous injection of 4.5 mg (n = 3) or 15 mg (n = 9) of bevacizumab-800CW. This clinical trial was divided into 2 parts. An interim analysis was performed after the inclusion of 3 patients per dose group (study part 1) to determine the more optimal dose. Then 6 additional patients were included with the optimal dose in study part 2. All patients underwent standard clinical imaging, including fundus photography, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. Fluorescence imaging was performed 1 min, 60 min, and 3-4 d after bevacizumab-800CW injection. Results: Bevacizumab-800CW injections were safe and well tolerated. One minute after injection, only the 15-mg group demonstrated a significantly higher contrast-to-noise ratio (median, 6.32) in vessels compared with baseline (median, -4.44; P = 0.0342). This, combined with the clear visual uptake after 3-4 d, supported 15 mg as the preferred dose. Contrast-to-noise ratio values inside the macula of patients receiving 15 mg of bevacizumab-800CW (n = 8) were significantly higher after 3-4 d (median, 4.45) compared with baseline (median, 0.19; P = 0.0078). Conclusion: Targeted fluorescent tracers such as bevacizumab-800CW can visualize VEGF expression, providing important insights into nAMD, and can pave the way toward personalized treatments and targeted drug development.

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Atezolizumab plus bevacizumab (ATEZO/BEV) and Lenvatinib (LEN) have demonstrated efficacy as first-line systemic therapies for unresectable hepatocellular carcinoma (HCC). This study aimed to compare the efficacy, safety, and outcomes of these two treatments. Data were retrospectively collected from 163 patients with unresectable HCC receiving first-line Lenvatinib (LEN) (n = 85) or ATEZO/BEV (n = 78) between 2020 and 2023 at Chulalongkorn University Hospital in Bangkok, Thailand. The primary outcome was overall survival (OS) following treatment. Propensity score matching (PSM) was used for analysis. The median patient age was 60.6 (SD 11.8) years; 82.2% were male. Most had hepatitis B/C (66.9%), BCLC stage C (73%), and Child-Pugh class A cirrhosis (63.8%). After PSM analysis, overall survival (OS) was significantly longer in the ATEZO/BEV group (12.7 vs. 7.5 months; p = 0.016, HR = 0.618, 95% CI: 0.417-0.916). However, there was no significant difference in progression-free survival (PFS) between ATEZO/BEV and LEN groups (10.8 vs. 7.8 months; p = 0.26, HR = 0.73, 95% CI: 0.431-1.255). Assessed by mRECIST, neither objective response rate (ORR: 23.7% vs. 19.7%, p = 0.555) nor disease control rate (DCR: 36.8% vs. 38.2%, p = 0.867) differed significantly. Multivariate analysis revealed alpha-fetoprotein ≥500 ng/mL (HR = 1.881, 95% CI: 1.028-3.443, p = 0.04), tumor size (HR = 1.833, 95% CI: 1.010-3.327, p = 0.046) and ATEZO/BEV therapy (HR = 0.604, 95%CI: 0.373-0.977, p = 0.04) were independently associated with OS. Adverse event rates were comparable (ATEZO/BEV 43.7% vs. LEN 56.3%; p = 0.08). In conclusion, the study demonstrates that ATEZO/BEV significantly improves OS compared to LEN in patients with unresectable HCC, despite similar PFS, ORR, and DCR. Both treatments have comparable safety profiles.

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Importance: Although pharmacovigilance signals and a strong pathophysiological rationale have suggested a potential risk of arterial dissections or aneurysms associated with angiogenesis inhibitors, this association deserves to be further investigated through clinical practice evidence studies. Objective: To evaluate the association between exposure to angiogenesis inhibitors and the occurrence of arterial dissections or aneurysms in patients treated for metastatic colorectal cancer (mCRC). Design, Setting, and Participants: A nested case-control study was conducted within a cohort of adults initiating targeted therapy (angiogenesis or epidermal growth factor receptor inhibitors) for mCRC between January 1, 2012, and December 31, 2017. Data were analyzed from April 2021 through August 2023. Data were drawn from the French nationwide Système National des Données de Santé database, which combines health insurance and hospital discharge records. Cases of arterial dissection or aneurysm were identified through 2019 and matched with up to 10 controls by age, sex, and time since cohort entry. Exposures: The angiogenesis inhibitors indicated for mCRC in France (ie, bevacizumab, aflibercept, ramucirumab, and regorafenib) were considered. Exposure was defined using 3 criteria: exposure at any point (exposed vs unexposed), recency (current, past, or unexposed), and cumulative duration of exposure (quartiles). Exposure periods were estimated using recommended administration schedules or drug elimination times. Main Outcomes and Measures: The primary outcome was incident hospitalization for arterial dissection or aneurysm, identified through hospital discharge diagnoses. Conditional logistic regression models were applied to estimate the association between exposure to angiogenesis inhibitors and the occurrence of arterial dissections or aneurysms, expressed as odds ratios (ORs) with 95% CIs. Results: Of the 34 733 patients included in the cohort, 195 incident cases (0.6%) were matched with 1950 controls. The study population (2145 patients) included 1562 male patients (72.8%); the median (IQR) age was 69 (63-73) years for cases and 68 (62-73) years for controls. Considering exposure at any point, 141 cases (72.3%) and 1381 controls (70.8%) were exposed to angiogenesis inhibitors; after adjustment for cardiovascular risk level, no association was observed between exposure and the occurrence of arterial events (OR, 1.07; 95% CI, 0.75-1.52). No associations were found with either recency or cumulative duration of exposure, regardless of the exposure estimation method. Conclusions and Relevance: In this case-control study of arterial dissections or aneurysms in patients receiving targeted therapy for mCRC, the lack of association with angiogenesis inhibitor exposure was reassuring, given the established benefits of these drugs, particularly bevacizumab, for this indication.

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BACKGROUND: Few treatment options are available for patients with epidermal growth factor receptor (EGFR) mutation-positive metastatic non-squamous non-small cell lung cancer (NSCLC) who failed treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). We aimed to assess the efficacy and safety of atezolizumab plus bevacizumab in these patients. METHODS: We conducted a single-arm, Simon's minimax two-stage adapted phase II study. Patients received atezolizumab 1200 mg plus bevacizumab 15 mg/kg once every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Between 14 August 2020 and 18 January 2021, 23 patients from seven sites in China were enrolled; all received study treatment. Twenty-two patients were evaluable for ORR. At data cut-off, median follow-up was 16.4 months. The confirmed ORR was 18.2% (4/22) per RECIST v1.1. The number of responders did not cross the predefined threshold (> 6 patients) for stage II enrollment. For the four responding patients, the median TTR and DOR were 1.4 and 6.4 months, respectively. Median PFS and OS were 2.8 and 14.1 months, respectively. Atezolizumab plus bevacizumab had acceptable tolerability without any new safety signals identified. All patients experienced at least one treatment-emergent adverse event (TEAE); four patients experienced serious TEAEs and one patient died of an unknown cause. CONCLUSIONS: The chemotherapy-free atezolizumab plus bevacizumab regimen had limited efficacy but an acceptable safety profile in this exploratory study. Although current data suggest that chemotherapy may still be important for patients who failed EGFR-TKIs, more treatment regimens with lower toxicity and higher efficacy for these patients, such as antibody-drug conjugates and bispecific antibodies, need to be explored in the future. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04426825.

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OBJECTIVE: To present a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) following atezolizumab and bevacizumab therapy and systematically review the literature on immune checkpoint inhibitor (ICI)-associated antibody-mediated central nervous system (CNS) inflammatory demyelinating diseases. BACKGROUND: While ICIs have transformed cancer treatment, they can trigger diverse neurological immune-related adverse events. Autoimmune demyelinating disorders remain uncommon, with sparse published cases linking ICIs to MOGAD. We report a novel case of MOGAD developing after administration of atezolizumab plus bevacizumab. METHOD: We conducted a retrospective chart review of the index case and performed a systematic literature review (January 1, 2001, to April 30, 2025) of reported antibody-mediated CNS demyelinating disorders associated with ICIs. RESULT: This represents the first documented MOGAD case during atezolizumab and bevacizumab treatment for hepatocellular carcinoma. The patient achieved a favorable response to intravenous methylprednisolone and immunoglobulin therapy. Further research is warranted to elucidate the pathogenesis underlying ICI-associated MOGAD.

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The effect of proteinuria, a side effect of bevacizumab (BV) treatment, on the subsequent rate of renal function decline in patients with colorectal cancer remains inconclusive. In this study, we conducted a retrospective cohort study of 204 patients with colorectal cancer aged 18 years or older who received BV at Kanazawa Medical University Hospital from January 2014 to October 2024. The patients were classified into 2 groups based on the highest urine protein test values after the start of BV administration: a proteinuria-positive group (urinary protein test 2+ or higher) and a proteinuria-negative group (urinary protein test <1+). The rate of decline in renal function (i.e., estimated glomerular filtration rate [eGFR] slope) from the start of BV to 2 months after completion of BV was compared between the 2 groups using generalized estimating equations. In a model adjusted for confounding factors such as baseline renal function, age, sex, use of drugs or diabetes medications affecting renal function, and total dose of BV, the rate of decline in renal function was significantly greater in the proteinuria-positive group compared with the proteinuria-negative group (eGFR slope in mL/min/1.73 m2/year: proteinuria-positive group: -2.80 [95% confidence interval, CI: -5.38 to -0.23]; proteinuria-negative group: -0.13 [95% CI: -2.55 to 2.28], p = 0.03). These results suggest that proteinuria, a side effect of BV treatment, is associated with a subsequent worsening rate of renal function decline in patients with colorectal cancer.

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BACKGROUND: The use of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC) remains limited to tumors harboring microsatellite instability (MSI); however, a subset of microsatellite stable (MSS) tumors features an MSI-like phenotype that could predict responses to ICIs combined with anti-angiogenesis agents. PATIENTS AND METHODS: In this single-arm phase II trial, 45 mCRC patients with a positive tumoral MSI-like gene expression signature (GES) progressing to at least one chemotherapy regimen were recruited from seven European sites within the MoTriColor framework. Of these, 24 and 21 were MSI and MSS, respectively, by standard assays. Patients received intravenous atezolizumab (1200 mg) plus bevacizumab (7.5 mg/kg) infusions in 21-day cycles until progression, unacceptable toxicity, or consent withdrawal. The main outcome measure was the objective response rate (ORR, RECIST 1.1). RESULTS: The median (interquartile range) age of participants was 63 (58-73) years, 51.1% were male, 60.0% had right-sided tumors, and 31.1% had liver metastases. The ORR in the whole (MSI-like) sample was 38.6% [95% confidence interval (CI) 24.4% to 54.5%]. Among patients with MSI and MSS tumors, the ORR was 65.2% (95% CI 42.7% to 83.6%) and 9.5% (95% CI 1.2% to 30.4%), respectively. In the MSS subgroup without liver metastasis, the ORR was 15.4% (95% CI 1.9% to 45.4%). Overall median progression-free survival was 6.4 (95% CI 4.1-21.2) months (23.2 and 4.0 months in patients with MSI and MSS tumors, respectively). Grade ≥3 adverse events related to atezolizumab and bevacizumab occurred in 5 (11.1%) and 10 patients (22.2%), respectively. There were two grade 5 adverse events, of which one (colonic hemorrhage) was related to bevacizumab. CONCLUSIONS: MSI-like GES does not identify a population with higher sensitivity to immune checkpoint plus angiogenesis inhibition. However, responses are promising in patients with MSI tumors and, to a lesser extent, in patients without liver metastasis regardless of MSI status.

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Sintilimab with a bevacizumab biosimilar has been proved to have promising antitumor activity in patients with unresectable hepatocellular carcinoma (HCC). Patients with advanced HCC also showed promising survival outcomes and substantial response rates with transarterial chemoembolization (TACE). The objective of this study was to investigate the initial clinical effectiveness and safety of combining sintilimab and a bevacizumab biosimilar (Sin + Bev) with TACE in treatment-naive patients with advanced HCC. This retrospective study included patients with advanced HCC who were treated with first-line Sin + Bev and TACE between June 2020 and January 2024. According to modified response evaluation criteria in solid tumors (mRECIST) criteria, we analyzed progression-free survival (PFS), overall survival (OS), and tumor response. Adverse events (AEs) were gathered as well. Cox proportional hazard regression models were used to determine prognostic factors affecting OS and PFS. Twenty-six patients were included. According to mRECIST, the objective response rate was 53.8% (14/26) and the disease control rate was 80.8% (21/26), including 1 patient with complete response (CR). The median follow-up was 28.9 months (IQR, 25.8-32.0). The median PFS and OS were 12.0 months (95% CI: 10.5-13.5) and 23.8 months (95% CI: 19.4-28.2), respectively. Child-Pugh and up-to-seven were both independently correlated with OS. The most frequent AEs included Pyrexia (7 cases) and Decreased neutrophil count (7 cases). Grade 4 AEs occurred in one patient as increased aspartate aminotransferase and alanine aminotransferase, but no 5 AEs were observed. The combination of sintilimab plus a bevacizumab biosimilar with TACE showed a significant therapeutic effect in patients with advanced HCC. Additionally, the AEs associated with this treatment were manageable.

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Purpose: To highlight serious adverse effects regarding intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, which is widely used for the treatment of retinal diseases, including two cases of post-injection endophthalmitis, one of which was complicated by rhegmatogenous retinal detachment, and one case of secondary cataract following a potentially unnecessary injection. Methods: A retrospective analysis of three cases that developed complications after intravitreal anti-VEGF therapy. Results: All cases resulted in a decline in best corrected visual acuity (BCVA) that required additional surgical procedures. Discussion: While intravitreal anti-VEGF therapy has become the standard in the treatment of various retinal pathologies, it is not without risks. This case series presents significant adverse outcomes, emphasizing the potential for severe anatomical and functional consequences. As the global volume of anti-VEGF intravitreal injections increases, so must our commitment to patient safety, precision in diagnosis, and ethical decision making. Conclusion: Although generally safe and commonly used in clinical practice, physicians must be aware of the risks of anti-VEGF therapy and must remain vigilant regarding patient selection and risk-benefit considerations.

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INTRODUCTION: Bevacizumab, an angiogenesis inhibitor, is commonly used alongside chemotherapy for metastatic colorectal cancer (mCCR). While inducing necrosis in tumours, bevacizumab may also lead to atrophy in tumour-free organs. Artificial intelligence (AI) models offer user-friendly methods for measuring organ volumes. This study explores the relationship between bevacizumab-induced atrophy using AI-assisted volume measurement in tumour-free organs and treatment efficacy. METHODS: This multicenter retrospective study includes patients from the PRODIGE 9 and PRODIGE 20 trials. Organ atrophy was assessed by evaluating volume changes from diagnosis to two months after treatment initiation in patients receiving bevacizumab compared to those who did not. Statistical analyses were performed using the Wilcoxon test, with correlations between volumetric changes. Overall and progression-free survival were assessed using log-rank tests and Cox regression models. RESULTS: Among the 214 patients included, 192 received bevacizumab. Both liver and spleen volumes were measured using a deep learning-based AI model and manual measurements. AI-generated volume measurements showed a strong correlation with manual measurements (Pearson coefficient > 0.8). Bevacizumab-treated patients exhibited significant atrophy of non-tumoural liver volume (p = 0.0378), while no significant changes were observed in tumour or spleen volumes in either group. Survival analyses revealed that patients with a smaller decrease in non-tumoural liver volume had improved overall survival (p = 0.016), although this association became non-significant after adjusting for age, sex, and tumour volume at diagnosis (p = 0.25). CONCLUSION: Our findings support the feasibility and reliability of AI in organ volume measurement. While bevacizumab exposure was linked to non-tumoural liver atrophy, its impact on survival remains inconclusive after adjustment. These results pave the way for further research into bevacizumab-induced organ atrophy and the potential of AI in personalizing oncology treatments.