Median Duration Of Response Research Articles

Potential of zoledronate for treating diffuse sclerosing osteomyelitis of the mandible in adult patients.

Diffuse sclerosing osteomyelitis (DSO) is a rare nonbacterial bone disease associated with recurrent pain and swelling, and its pathogenesis remains unknown. Despite the absence of an established treatment for DSO, bisphosphonates have recently been considered effective in managing this condition. However, the use of zoledronate is off-label, with limited reported cases. Therefore, this study aimed to investigate the effects of zoledronate on pain suppression in DSO. This single-arm retrospective study evaluated adult patients diagnosed with mandibular DSO and treated with zoledronate. Patient demographics, pain suppression effect, recurrence, number of zoledronate administration, adverse reactions to zoledronate, and imaging findings were investigated. The study included 18 patients (median age of 59.5years). Zoledronate effectively suppressed pain in all patients, with a median duration of effect onset of 1day. Symptom recurrence was observed in 66.7% of patients, with a median time of 29months from the first zoledronate administration to recurrence. Zoledronate was administered multiple times to 44.7% of patients. The median duration of response was 80months for patients who experienced relief after a single administration of zoledronate compared to 32months for those who received multiple administrations (p < 0.001). Adverse reactions, including flu-like symptoms, were observed in 72.2% of the patients, and no medication-related osteonecrosis of the jaw was observed during the follow-up period. Zoledronate is a relatively safe and effective treatment option for DSO of the mandible. Key Points • Zoledronate effectively suppresses pain in mandibular diffuse sclerosing osteomyelitis. • All condylar lesions recurred after zoledronate administration. • Patients with mandibular canal enlargement required multiple doses of zoledronate. • Adverse reactions to zoledronate administration were minor.

Gamma-hydroxybutyrate to promote slow-wave sleep in major depressive disorder: a randomized crossover trial.

In major depressive disorder (MDD), main clinical features include insomnia and increased daytime sleepiness. However, specific treatment options to promote sleep in MDD are limited. Gamma-hydroxybutyrate (GHB, administered as sodium oxybate) is a GHB/GABAB receptor agonist used clinically in narcolepsy, where it promotes restorative slow-wave sleep (SWS) while reducing next-day sleepiness. Hence, we performed a randomized, placebo- and active comparator-controlled, double-blind, crossover trial to investigate the sleep-promoting properties of GHB in individuals with MDD. Outpatients aged 20-65 years fulfilling the DSM-5 criteria for MDD were enrolled. A single nocturnal dose of GHB (50 mg/kg) was compared with a single evening dose of the clinical competitor trazodone (1.5 mg/kg) and placebo. Of 29 randomized patients, 23 received at least one intervention and were included in the analysis. Primary outcomes were nocturnal slow wave sleep ([SWS] assessed by polysomnography), next-day vigilance (median response time and number of lapses on the psychomotor vigilance test [PVT]), next-day working memory (median speed and accuracy on an N-back task), and next-day plasma brain-derived neurotrophic factor (BDNF) levels. GHB robustly prolonged SWS compared to both trazodone and placebo. GHB also prolonged total sleep time and enhanced sleep efficiency, while reducing sleep stages N1, N2, and wake-after-sleep-onset. While the median response time on the next-day PVT was unaffected, GHB reduced the number of lapses compared to trazodone and placebo. No effects on next-day working memory performance and BDNF levels were observed. No serious adverse events occurred. Overall, a single nocturnal dose of GHB effectively promotes SWS and shows more favorable effects on next-day vigilance than trazodone and placebo. Future studies should investigate GHB in clinical settings, including repeated administration.

Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial.

Chemotherapy remains a standard treatment option for metastatic triple-negative breast cancer (TNBC) but is associated with limited survival. Although some targeted antibody-drug conjugates have demonstrated clinical benefits and are considered standard therapy, persistent unmet medical needs remain due to varying accessibility. The OptiTROP-Breast01 phase 3 trial assessed sacituzumab tirumotecan (sac-TMT) versus chemotherapy in patients with locally recurrent or metastatic TNBC who had received two or more prior therapies, including at least one for metastatic disease. Patients were randomized to sac-TMT (n = 130) or chemotherapy (n = 133). The primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) was met based on the protocol-specified interim analysis. At final analysis, the median PFS by BICR was 6.7 (95% confidence interval (CI), 5.5-8.0) months with sac-TMT and 2.5 (95% CI, 1.7-2.7) months with chemotherapy (hazard ratio (HR), 0.32; 95% CI, 0.24-0.44; P < 0.00001). Concurrently, at the protocol-specified interim analysis for overall survival (OS), the median OS was not reached (95% CI, 11.2 months to not estimable (NE)) with sac-TMT and 9.4 (95% CI, 8.5-11.7) months with chemotherapy (HR, 0.53; 95% CI, 0.36-0.78; P = 0.0005). The percentage of patients with an objective response was 45.4% with sac-TMT and 12.0% with chemotherapy. The median duration of response was 7.1 (95% CI, 5.6-NE) months with sac-TMT and 3.0 (95% CI, 2.5-NE) months with chemotherapy. The most common treatment-related adverse event with sac-TMT was hematologic toxicity. Sac-TMT demonstrated statistically significant and clinically meaningful improvements in PFS compared to chemotherapy, with a manageable safety profile. The study findings support sac-TMT as an additional effective treatment option for pretreated metastatic TNBC. ClinicalTrials.gov identifier: NCT05347134 .

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization in patients with unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study.

Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have poor overall survival (OS). Hepatic arterial infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE), including conventional TACE (c-TACE) and drug-eluting bead TACE (DEB-TACE), are widely used to treat ICC, but the efficacy of these therapies has not been fully demonstrated. This study aimed to compare the efficacy of HAIC and TACE in unresectable ICC patients. This retrospective cohort study included unresectable ICC patients who received HAIC, c-TACE or DEB-TACE as initial treatment between June 2016 and October 2023 at three hospitals. The median OS (mOS), tumor response, and incidence of adverse events (AEs) were compared and propensity score matching (PSM) was used to reduce selection bias. A total of 181 patients with unresectable ICC received HAIC (n = 24), c-TACE (n = 73) and DEB-TACE (n = 84). The HAIC group had significantly higher mOS (10.3 vs. 5.1 months, p = 0.0042), objective response rate (ORR) (29.2% vs. 4.1%, p = 0.002) and disease control rate (DCR) (95.8% vs. 43.8%, p < 0.001) than the c-TACE group. There was no significant difference between the HAIC and DEB-TACE groups in improving mOS (10.3 vs. 12.5 months, p = 0.61). Results remained consistent after PSM. The c-TACE and DEB-TACE groups had a higher incidence of AEs compared with the HAIC group. After matching, there was no significant difference in the incidence of AEs between groups. HAIC improves ICC patient prognosis better than c-TACE. Both HAIC and DEB-TACE are superior treatment options for unresectable ICC. Question The evidence of comparative effectiveness between hepatic arterial infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE) is insufficient. Findings HAIC significantly improved median overall survival, tumor response, and prognosis while reducing adverse events compared to convention TACE (c-TACE) in unresectable intrahepatic cholangiocarcinoma (ICC) patients. Clinical relevance HAIC significantly improves OS and tumor response in patients with unresectable ICC compared to c-TACE, but HAIC shows no significant difference from drug-eluting bead-TACE. Notably, HAIC shows no significant difference in adverse events compared to both c-TACE and DEB-TACE.

Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial.

In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02+ patients with PRAME+ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose for extension. Secondary objectives include the evaluation of IMA203 TCR-engineered T cell persistence in peripheral blood, tumor response as well as duration of response. A total of 27 patients were enrolled in the phase 1a dose escalation and 13 patients in the phase 1b dose extension. IMA203 T cells were safe, and the MTD was not reached. Of the 41 patients receiving treatment (that is, who started lymphodepletion), severe cytokine release syndrome was observed in 4.9% (2/41), and severe neurotoxicity did not occur. In the 40 patients treated with IMA203, an overall response rate consisting of patients with unconfirmed or confirmed response (u/cORR) of 52.5% (21/40) and a cORR of 28.9% (11/38) was observed with a median duration of response of 4.4 months (range, 2.4-23.0, 95% confidence interval: 2.6-not reached) across multiple indications. Rapid T cell engraftment and long-term persistence of IMA203 T cells were observed. IMA203 T cells trafficked to all organs, and confirmed responses were more frequent in patients with higher dose. T cell exhaustion was not observed in the periphery; deep responses were enriched at higher PRAME expression; and higher T cell infiltration resulted in longer progression-free survival. Overall, IMA203 showed promising anti-tumor activity in multiple solid tumors, including refractory melanoma. ClinicalTrials.gov identifier: NCT03686124 .

PD-1 Inhibition for Relapse after Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Relapse of AML and MDS remains the primary source of mortality after allogeneic transplantation (HCT). Targeting PD-1 is an approach for reversing T cell exhaustion and restoring the graft-versus-leukemia (GVL) effect that has logistical advantages versus donor lymphocyte infusion. In a prospective phase 1B clinical trial, pembrolizumab monotherapy was administered every three weeks to sixteen AML (n=12) and MDS (n=4) patients in relapse after HCT to assess Graft-versus-Host Disease (GVHD), clinical response and survival. The median time to relapse after HCT was 5.5 months and the median pre-treatment bone marrow blast percentage was 21.5%. The overall response rate (ORR) was 31.3% for patients receiving pembrolizumab monotherapy, consisting of three complete remissions (18.8%) and two partial remissions (13.5%). The median duration of response was 610 days. A significantly greater proportion of patients with mixed CD3 chimerism had clinical response compared to those with full donor chimerism (50% vs. 0%; p=0.03). Immune toxicities were frequent with 37.5% patients developing severe (grade III-IV) GVHD after pembrolizumab, of which the majority had resistance to corticosteroids and contributed to death in four patients (25%). The one-year overall survival was 37.5% and event-free survival was 31.3%. For AML, one-year overall survival was 50.0%. In this trial, PD-1 inhibition led to durable remissions in a third of patients experiencing early relapse after HCT suggesting this approach may augment the GVL response. Responses were exclusively observed in the setting of mixed CD3 donor chimerism. Immune toxicities (GVHD) were a barrier to successful treatment outcome. NCT03286114.

Donor-derived CARCIK-CD19 cells engineered with Sleeping Beauty transposon in acute lymphoblastic leukemia relapsed after allogeneic transplantation

Non-viral engineering can ease CAR-T cell production and reduce regulatory and cost requirements. We utilized Sleeping Beauty transposon to engineer donor-derived anti-CD19.CD28.OX40.CD3zeta T cells differentiated in cytokine-induced killer (CARCIK-CD19) for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients relapsed after allogeneic hematopoietic stem cell transplantation (alloHSCT). We report the results of CARCIK-CD19 observed in 36 patients (4 children and 32 adults) treated according to the final recommended dose. Cytokine release syndrome of grade 2 or lower occurred in 15 patients, ICANS grade 2 in 1 patient, and late-onset peripheral neurotoxicity of grade 3 in 2 patients. GVHD never occurred after treatment with allogeneic CARCIK-CD19. Complete remission was achieved by 30 out of 36 patients (83.3%), with MRD negativity in 89% of responders. With a median follow-up of 2.2 years, the 1-year overall survival was 57.0%, and event-free survival was 32.0%. The median duration of response at 1 year was 38.6%. CAR-T cells expanded rapidly after infusion and remained detectable for over 2 years. Integration site analysis after infusion showed a high clonal diversity. These data demonstrated that SB-engineered CAR-T cells are safe and induce durable remission in heavily pretreated patients with BCP-ALL relapsed after alloHSCT. Trial registration: The phase 1/2 and phase II trials are registered at www.clinicaltrials.gov as NCT#03389035 and NCT#05252403.

Total Skin Irradiation in the Treatment of Primary Cutaneous Lymphomas: a Literature Review and Clinical Cases

Introduction: Primary cutaneous lymphomas represent a heterogeneous group of diseases, the treatment of advanced stages of which requires a comprehensive approach, including systemic therapy and skin-directed methods. Total skin electron irradiation (TSEB) demonstrates high efficacy due to the radiosensitivity of lymphoid cells. Despite the high overall response rate, the recommended dose ranges and fractionation schemes for TSEB vary, necessitating detailed investigation. Stratification of patients by clinical stage, type of lesions, and the extent of skin involvement is crucial for optimizing TSEB, improving outcomes, and reducing side effects.Total skin electron beam radiotherapy: A Trend Toward Low Doses: TSEB with cumulative doses of 30ʹ36 Gy has established itself as an effective treatment method; however, there is growing interest in lower doses (10ʹ29 Gy) due to the high radiosensitivity of lymphomas and the need to reduce radiation-related side effects. Studies have confirmed a high overall response to low doses, especially in early stages, with less pronounced radiation reactions and a comparable median duration of response. To optimize the approach, further research is needed, including the development of patient selection criteria and dose individualization with a potential boost to large lesions.Conclusions: The question of the optimal cumulative dose for TSEB in patients with primary cutaneous lymphomas remains insufficiently studied. Clinical cases confirm the efficacy of both standard doses (30ʹ36 Gy) and low doses (10ʹ20 Gy), demonstrating good clinical responses, symptom reduction, and lower toxicity. Low dose TSEB provides a comparable overall response to standard doses, reduces the number of treatment visits, and enables retreatment in case of disease relapse. The main tasks remain to study the factors influencing dose selection (disease stage, type of lesions, individual patient characteristics) and to develop patient management strategies. TSEB effectively controls disease manifestations even in complex cases. Data analysis highlights the need for unified patient selection criteria and optimization of irradiation techniques to improve outcomes and reduce treatment toxicity.

Safety and Activity of Fibroblast Growth Factor Receptor Inhibitors in Advanced Malignancies: A Pooled Analysis of Early-Phase Clinical Trials.

Aberrant signaling through the fibroblast growth factor receptor (FGFR) due to activating somatic alterations has been associated with multiple malignancies. FGFR inhibitors (FGFRi) with distinct profiles recently entered standard of care. This work summarizes the experience of a dedicated clinical trial unit with FGFRi developed in the last decade within the context of clinical trials. Demographic and clinical data were collected for patients enrolled in FGFR-targeting phase I to II trials conducted at Sarah Cannon Research Institute, United Kingdom between January 2012 and August 2023. Fifty-four patients across seven trials were identified: 50% male; median age 55 years. An FGFR alteration was present in 81% of cases; rearrangements, amplifications, and mutations were present in 59%, 43%, and 9.1% of the cases, respectively, with coexisting alterations in 27%. The most frequent primary tumors were cholangiocarcinomas (31%), urothelial (15%), and colorectal (15%); 85% of the patients were FGFRi-naïve. The most common adverse events (AEs) were hyperphosphatemia (42%), dry mouth (35%), fatigue (24%), mucositis (24%), nail changes (22%), and palmar-plantar erythrodysesthesia (20%), with significant differences between pan-FGFRi and FGFR-2i. The rate of G3 AEs was 22%; no G4-5 events were observed. The median time on treatment was 3.5 months (0.2-72.8). Higher disease control rate was observed in the presence of any FGFR alteration, compared with all-comers (odds ratio [OR], 7; P = .0226). The objective response rate was 38%, 25%, and 25% in patients with gene rearrangements, amplification, and mutations, respectively. The median duration of response was 2.3 months (1.6-7.7). After a median follow-up time of 20 months (95% CI, 12.9 to 71.8), median progression-free survival (mPFS) was 3.2 months (95% CI, 1.9 to 4.6) and median overall survival was 13 months (95% CI, 6.4 to 19.6). PFS was significantly different by response, FGFR status, and tumor type. Patients who experienced a G2-3 AE were more likely to achieve a response (OR, 5.24; P = .0256). FGFRi are effective treatment strategies for patients with advanced solid tumors harboring FGFR alterations, with manageable toxicities in most patients.

Clinical significance of the dose modification of enfortumab vedotin monotherapy for advanced urothelial carcinoma.

This study aimed to assess the influence of modifying the dose of enfortumab vedotin (EV) monotherapy in patients with advanced urothelial carcinoma (UC). We retrospectively evaluated consecutive patients with metastatic UC who had received EV following platinum-based chemotherapy and immune checkpoint inhibitor therapy at our institution between December 2021 and June 2024. The relative dose intensity (RDI), the reason for dose adjustments, and the overall survival (OS) were analyzed. Overall, 49 patients were enrolled, of which 16 (32.7%), 21 (42.9%), and 12 (24.4%) had RDI of >80%, 60%-80%, and<60%, respectively. EV was discontinued in 3 (6.1%), interrupted in 22 (44.9%), and reduced in dose in 26 (53.1%) patients. In particular, EV was interrupted because of adverse events (AEs) in 77% of patients, and patient preference or attending physician's discretion in 23%. EV dose reduction occurred in 77% of patients because of AEs and in 23% because of the attending physician's discretion. The median duration of EV exposure in patients with RDI of >80%, 60%-80%, and<60% was 3.8, 4.8, and 7.8months, respectively. These three groups showed no significant difference in OS from EV introduction (median, 8.8months vs. 12.9months vs. 15.1months; P=.104). The median duration of EV response was 9.9months in patients with RDI<60%. In cases of effective management, decreasing the RDI during EV monotherapy does not negatively impact the survival outcomes.

Trends in Program Satisfaction and Confidence Levels Among United States Radiation Oncology Residents: A Five-Year Aggregate Analysis of the 2020-2024 ARRO Graduating Resident Survey.

Trends in Program Satisfaction and Confidence Levels Among United States Radiation Oncology Residents: A Five-Year Aggregate Analysis of the 2020-2024 ARRO Graduating Resident Survey.

Cemiplimab plus peltopepimut-S vaccine in recurrent cervical cancer: A phase 2 clinical trial.

Cemiplimab plus peltopepimut-S vaccine in recurrent cervical cancer: A phase 2 clinical trial.

Phase I, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients With Metastatic Castration-Resistant Prostate Cancer

PURPOSE FOR46, a fully human antibody conjugated to monomethyl auristatin E, targets a tumor-selective epitope of CD46, which is overexpressed in metastatic castration-resistant prostate cancer (mCRPC). FOR46 demonstrates potent nonclinical activity in enzalutamide-resistant CRPC models. PATIENTS AND METHODS This was a phase I, first-in-human, dose escalation/expansion study in patients with progressive mCRPC after treatment with ≥one androgen signaling inhibitors (ClinicalTrials.gov identifier: NCT03575819 ). The starting dose of FOR46 was 0.1 mg/kg given intravenously every 3 weeks. The primary objective was to determine the maximally tolerated dose (MTD). Whole-blood mass cytometry (cytometry by time of flight) was used to characterize peripheral immune response and CD46 expression in CRPC tissue that underwent central pathology review. RESULTS Fifty-six patients were enrolled. Dose-limiting toxicities included neutropenia (n = 4), febrile neutropenia (n = 1), and fatigue (n = 1). The MTD was 2.7 mg/kg using adjusted body weight. The most common grade ≥3 adverse events across all dose levels were neutropenia (59%), leukopenia (27%), lymphopenia (7%), anemia (7%), and fatigue (5%). One grade 3 febrile neutropenia event was observed. There were no treatment-related deaths. In the efficacy evaluable subset (patients with adenocarcinoma treated with a starting dose ≥1.2 mg/kg, n = 40), the median radiographic progression-free survival was 8.7 months (range, 0.1-33.9). Fourteen of 39 evaluable patients (36%) achieved a PSA50 response. The confirmed objective response rate was 20% (5 of 25 RECIST-evaluable patients). The median duration of response was 7.5 months. Responders had a significantly higher on-treatment frequency of circulating effector CD8 + T cells. CONCLUSION FOR46 demonstrated encouraging preliminary clinical activity with a manageable safety profile. Targeting CD46 elicited an immune priming effect that was associated with clinical outcomes.

INO-CD22: A multicenter, real-world study of inotuzumab ozogamicin safety and effectiveness in adult patients with relapsed/refractory acute lymphoblastic leukemia.

Inotuzumab ozogamicin (IO) has helped to change the treatment paradigm in B-cell acute lymphoblastic leukemia (B-ALL) but real-world data are limited. The INO-CD22 study is a multicenter retrospective cohort study of adult patients with relapsed/refractory B-ALL treated with IO in 24 Italian centers from 2014 to 2019, with the aim of assessing the response, survival, and toxicity of IO. Data for 73 eligible patients were obtained: the median age at the start of IO treatment was 52.7 years (I-III quartiles, 51.9-53.5 years), the median number of previous lines was three (I-III quartiles, two to four), and prior exposure to induction standard chemotherapy and blinatumomab occurred in 85% and 57.5% of cases, respectively. IO was administered following the label schedule. A 74.0% overall response rate was achieved, with a 69.8% complete remission rate and a 4.1% complete remission with incomplete hematologic reconstitution rate. The median duration of response was 4.4 months (I-III quartiles, 2.3-11.2 months). With a median follow-up of 37.2 months, the median overall survival (OS) was 7.9 months (95% CI, 6.08-12.42 months) with a 3- and 5-year OS of 21.2% (95% CI, 11.9%-32.3%) and 5.3% (95% CI, 9.6%-29.8%), respectively. Overall, 37% of patients were able to proceed to allogeneic hematopoietic stem cell transplantation. Eight patients (11.0%) experienced veno-occlusive disease/sinusoidal obstruction syndrome; the most frequent grade ≥3 nonhematologic adverse events were liver toxicities and pneumonia (two grade 4 and one grade 5, respectively). Despite the limitations of retrospective studies, the INO-CD22 study highlights the favorable safety profile and clinical activity of IO within a real-world context.

Pembrolizumab in Patients of Chinese Descent with Microsatellite Instability-high/Mismatch Repair Deficient Advanced Solid Tumors: KEYNOTE-158 Final Analysis.

KEYNOTE-158 (NCT02628067) supported the US Food and Drug Administration approval of pembrolizumab for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors. Incidence of MSI-H/dMMR tumors in patients of Chinese descent is similar to that of Western populations. CohortL of KEYNOTE-158 evaluated pembrolizumab in patients of Chinese descent with previously treated MSI-H/dMMR tumors. We previously reported an objective response rate (ORR) of 70% in 20 patients from cohortL which supported the approval in China of pembrolizumab in patients with MSI-H/dMMR solid tumors. Here we present results of the final analysis for 30 patients with median follow-up of 18months. Eligible patients who had confirmed unresectable or metastatic MSI-H/dMMR tumors, and one or more prior lines of therapy, received 200mg pembrolizumab Q3W (up to 35 cycles) until progression, toxicity, or withdrawal. Primary endpoint was ORR per RECIST1.1 by central review. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Thirty patients were enrolled; 7 (23%) were aged ≥ 65years, and 20 (67%) were female. With median follow-up of 18months, ORR was 66.7%. Median DOR was not reached (NR), with 12-month DOR rate of 85.9%. Median PFS was NR, with 18-month PFS rate of 63.0%. Median OS was NR, with 18-month OS rate of 78.8%. Treatment-related adverse events (AE) were reported in 22 (73%) patients. Grade3-4 treatment-related AEs occurred in 7 (23%) patients. Immune-mediated AEs occurred in 11 (37%) patients of which 2 (7%) had grade3 AEs. No grade ≥ 4 immune-mediated AEs occurred. Pembrolizumab continues to provide clinically meaningful antitumor activity and durable responses with a manageable safety profile in patients of Chinese descent with MSI-H/dMMR advanced solid tumors. These results are consistent with those reported for patients in the global population and further support the use of pembrolizumab in patients of Chinese descent with MSI-H/dMMR tumors. TRIALREGISTRATIONNUMBER: NCT02628067.

Riluzole in Combination with mFOLFOX6 and Bevacizumab in Treating Patients with Metastatic Colorectal Cancer: A Phase 1 Clinical Trial.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the US. 5-fluorouracil (5-FU)-based chemotherapies in combination with targeted agents remain the standard of care in patients with metastatic or locally advanced disease. New treatment strategies are needed for metastatic CRC patients with microsatellite stable disease. Preclinical studies showed that riluzole, an oral medicine for amyotrophic lateral sclerosis, inhibits glutamate release and synergizes with 5-FU to reduce cell viability in CRC cell lines. In this single-arm, phase 1 trial of riluzole in combination with mFOLFOX6/bevacizumab for patients with metastatic CRC, the riluzole dose started at 50 mg twice daily, escalating to 100 mg twice daily or de-escalating to 50 mg once daily. Patients received riluzole for 16 weeks in combination with mFOLOFX6/bevacizumab for 8 cycles. Patients then either continued mFOLFOX6/bevacizumab or switched therapy. Twelve of the 14 patients enrolled were evaluable. All patients previously received FOLFOX, and 5 patients (41.7%) showed disease resistance to it. Two patients obtained partial responses, 9 had stable disease, and 1 had progressive disease. The objective response rate was 16.7%, and the disease control rate was 91.7%. The median duration of response was 4.9 months (95% CI 1.6-9.8). Median progression-free survival and overall survival were 4.89 and 12.98 months, respectively. Our study showed that riluzole plus mFOLFOX6/bevacizumab is well tolerated in patients with metastatic CRC and may have clinical activity in patients whose disease is resistant to FOLFOX.

Impact of a pharmacogenomics (PGx) clinic on patient satisfaction and PGx literacy.

Genetic variants can impact medication response. The study of genetic variants on medications is called pharmacogenomics (PGx). Understanding PGx results can be difficult as results are reported differently than other laboratory tests. Patients have reported a lack of understanding and satisfaction with PGx information. Surveys were emailed to patients seen in the PGx clinic and patients who participated in an elective screening (Sanford Chip) at Sanford Health. Surveys were conducted to assess literacy, understanding and satisfaction of PGx testing. Survey responses were summarized using descriptive statistics. There were 121 responses that were initially collected. A total of 100 responses were included in the analysis. The median response amongst all individuals was 9 out of a possible 13 points on the PGx literacy assessment. PGx clinic patients had increased satisfaction compared to Sanford Chip patients for being able to understand results (p < 0.05), that PGx test provided information to improve my care plan (p < 0.05), that they feel confident that my medication will be effective for me based on my genetics (p < 0.05), were satisfied with communication of results (p < 0.001) and overall experience (p < 0.01). Implementation of a PGx clinic improves patient experience, confidence, and satisfaction.

Phase I study of the mutant IDH1 inhibitor ivosidenib: long-term safety and clinical activity in patients with conventional chondrosarcoma.

A phase I study demonstrated that ivosidenib, a mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, showed manageable toxicity and durable disease control in patients with mIDH1 conventional chondrosarcoma (CS). Here we present long-term follow-up data on the safety and clinical activity of ivosidenib in patients with mIDH1 conventional CS from this phase I study. This phase I open-label dose-escalation and expansion study assessed ivosidenib monotherapy in patients with advanced mIDH1 solid tumors, including CS. An ivosidenib dose of 500 mg/day was identified in the dose-escalation phase and used for the expansion phase. The primary outcome was safety and tolerability. Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). The database lock date for this analysis was 18 March 2024. Of 168 patients with advanced mIDH1 solid tumors receiving ivosidenib in this study, 21 patients had CS, of which 13 had conventional histology. Six (46.2%), 4 (30.8%) and 3 (23.1%) patients with conventional CS continued ivosidenib treatment for >1 year, >6 years and >7 years, respectively. Of the 21 patients with CS, 71.4% and 28.6% had treatment-related and serious adverse events (SAEs), respectively, but no SAEs were considered related to ivosidenib. The ORR for patients with conventional CS was 23.1% and median duration of response was 53.5 months. The median PFS of patients with conventional CS treated with ivosidenib was 7.4 months. Ivosidenib demonstrated long-term disease control and manageable toxicity for some patients with mIDH1 conventional CS and is under further investigation (NCT06127407).

Eribulin efficacy in long responder patients with metastatic breast cancer: A multicentric observational study.

Eribulin efficacy in long responder patients with metastatic breast cancer: A multicentric observational study.

Gender Differences in Patient-Physician Communication in Ophthalmic Practice, Pre- and Post-Covid 19.

Gender Differences in Patient-Physician Communication in Ophthalmic Practice, Pre- and Post-Covid 19.