Cause Of Treatment Discontinuation Research Articles

Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials

BackgroundRett syndrome (RTT) is a rare, life-threatening, genetic neurodevelopmental disorder. Treatment in RTT encounters many challenges. Trofinetide, a modified amino-terminal tripeptide of insulin-like growth factor 1, has demonstrated clinically promising results in RTT. In this study, trofinetide efficacy and safety in RTT are systematically reviewed and meta-analyzed.MethodsA systematic search of five electronic databases was conducted until January 2024. Review Manager 5.4 software was used for the analysis. The analysis was based on a weighted mean difference and standard error with a confidence interval (CI) of 95%, and a statistically significant P-value was considered if it was < 0.05. The study was registered on PROSPERO with registration number CRD42024499849. Quality of evidence was assessed using GRADE.ResultsThree randomized controlled trials (RCTs) with 276 patients were included in the analysis. Trofinetide improved both caregiver outcomes and clinical scales by improving the Rett Syndrome Behavior Questionnaire (RSBQ) (mean difference (MD): − 3.46 points, 95% CI: − 5.63 to − 1.27, P = 0.0002) and Clinical Global Impression Scale–Improvement (CGI-I) (MD: − 0.35, 95% CI: − 0.51 to − 0.18, P < 0.0001), respectively. However, trofinetide neither improved the Caregiver Top 3 Concerns Visual Analog Scale nor the Rett Motor Behavioral Assessment. Regarding safety, trofinetide was significantly associated with vomiting compared to placebo (odds ratio (OR): 3.17, 95% CI: 1.57 to 6.43, P = 0.001). After solving heterogeneity, results showed a statistically significant incidence of diarrhea in the trofinetide (200 mg) group compared to placebo (OR: 18.51, 95% CI: 9.30 to 36.84, P ≤ 0.00001).ConclusionsTrofinetide demonstrated statistically significant improvements in CGI-I and RSBQ in pediatrics and adult patients with Rett. Side effects are limited to vomiting and diarrhea. Although diarrhea yielded an insignificant result in our analysis, it emerged as a cause for treatment discontinuation in the participating trials, and a statistically significant risk for diarrhea emerged when excluding the study using a lower dose of the drug, hence causing heterogeneity, in the meta-analysis. Given the diverse genetic landscape of RTT, future RCTs investigating correlations between RTT genotype and phenotypic improvements by trofinetide will be beneficial. RCTs encompassing male patients with larger and longer cohorts are recommended.Graphical

Pirfenidone in Idiopathic Pulmonary Fibrosis: Real-World Observation on Efficacy and Safety, Focus on Patients Undergoing Antithrombotic and Anticoagulant.

Idiopathic pulmonary fibrosis (IPF) is a rare and progressive interstitial lung disease characterized by irreversible distortion of lung architecture and subsequent loss of pulmonary function. Pirfenidone is an antifibrotic agent associated with increased progression-free survival and overall survival rates, but it carries multiple side effects. The aim of the study was to examine the efficacy and safety profile of pirfenidone in a real-life context, with a focus on the concomitant use of antithrombotic and/or anticoagulant treatments. The clinical and functional data (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], diffusing lung capacity for carbon monoxide [DLCO], and 6 min walking test distance [6MWD]) of all IPF patients treated with pirfenidone and referred to our two centers between 2019 and 2022 were retrospectively analyzed at baseline, 6 and 12 months after the start of treatment. A total of 55 IPF subjects undergoing pirfenidone treatment were included in the analysis (45.5% females, median [IQR] age at disease onset 68.0 [10.0] years, median [IQR] age at baseline 69.0 [10.8] years). Compared to baseline, at 12 months, FVC (86.0% vs. 80.0%; p = 0.023) and DLCO (44.0% vs. 40.0%; p = 0.002) were significantly reduced, while FEV1 (p = 0.304) and 6MWD (p = 0.276) remained stable; no significant change was recorded at 6 months. Most of the reported adverse events were mild or moderate. Gastrointestinal intolerance (9.1%) was the main cause of treatment discontinuation. A total of 5% of patients reported at least one minor bleeding event, although all episodes occurred in those receiving concomitant antithrombotic or anticoagulant. Overall, this real-life experience confirms the efficacy and safety profile of pirfenidone in the case of the concomitant use of antithrombotic and/or anticoagulant drugs.

Long-term effectiveness, safety, and tolerability of doravirine in antiretroviral-experienced people with HIV in real life.

Real-life data on doravirine (DOR) in different drug combinations are limited. We evaluated the effectiveness of DOR plus two nucleos(t)ide reverse transcriptase inhibitors (NRTI), mainly abacavir/lamivudine, and dual therapies in people with HIV (PWH), mostly virologically suppressed. Ambispective observational study that enrolled adults PWH who initiated a DOR-based regimen from September 2020 to February 2022 at a referral center in Spain. Participants were grouped as follows: A, received DOR plus two NRTI; B, dual therapy (DT) with DOR plus dolutegravir (DTG) or darunavir/cobicistat (DRVc); C, DOR plus ≥two antiretroviral drugs. The primary endpoints were treatment effectiveness at week 48 by intention-to-treat (ITT) and per-protocol analysis (OT). A cohort of 187 participants, 91% virologically suppressed, were analyzed after a median follow-up of 112 weeks (80-136). Group A received DOR plus abacavir/lamivudine (ABV/3TC) (n = 109) or tenofovir/emtricitabine (TFV/3TC) (n = 45). At week 48, the effectiveness of DOR plus ABV/3TC by ITT was 90.8% (CI95, 88.0-93.6), better than with TFV/FTC [73.3% (66.7-79.9); P = 0.003]. Only one virologic failure was observed. Mild adverse effects were the cause of treatment discontinuation in 7.8%, followed by switching to a single-tablet regimen. In group B, the effectiveness by ITT was 92.9% (CI95, 88.0-97.8) at week 48. No adverse effects or virologic failure were registered in this group. DOR plus two NRTI or DT have long-term effectiveness and safety as a switching option for PWH, mostly virologically suppressed. The DOR plus ABV/3TC combination has shown even better effectiveness than TFV/FTC.IMPORTANCEDOR-based regimens have shown long-term effectiveness and safety in PWH, mostly virologically suppressed. The combination of DOR plus ABV/3TC has shown even better safety and effectiveness than TFV/FTC. DOR plus two NRTI offers cost benefits compared to other regimens.

One Year of Long-Acting Cabotegravir and Rilpivirine in People With Human Immunodeficiency Virus and Long Exposure to Antiretroviral Therapy: Data From the SCohoLART Study.

The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40-56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8-20.5) and 11.4 (7.9-17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2-4). During a median study follow-up (IQR) of 13.1 (9.1-15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%-14%). The main cause of TD was injection site reaction (15 participants [28.8%]). The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.

Scalp Nerve Block Alleviates Headaches Associated With Sonication During Transcranial Magnetic Resonance-Guided Focused Ultrasound.

In magnetic resonance-guided focused ultrasound (MRgFUS) procedures, headache is a frequent symptom and cause of treatment discontinuation. Herein, we assessed the efficacy of scalp nerve block (SNB) for alleviating headache during MRgFUS procedures. The effect of SNB on intraprocedural headache was examined by retrospectively comparing 2 patient cohorts at a single institution. During the study period from April 2020 to February 2022, an SNB protocol for all patients with a skull density ratio ≤0.55 was instituted on October 6, 2021. The number of patients with a skull density ratio ≤0.55 was 34 before the protocol and 36 afterward. Headache intensity was evaluated using a numerical rating scale (NRS) after each sonication. To evaluate the effect of SNB on headache intensity, multiple regression analysis was performed per patient and per sonication. In the per-patient analysis, the effect of SNB was evaluated using the maximum NRS, mean NRS, and NRS at the first ultrasound exposure that reached 52.5°C. In the per-sonication analysis, the effect of SNB was evaluated not only for the entire sonication but also for sonications classified into ≤9999 J, 10 000 to 29 999 J, and ≥30 000 J energy doses. With SNB, headache alleviation was observed in the NRS after the first sonication that reached 52.5°C in each patient (β = -2.40, 95% CI -4.05 to -0.758, P = .00499), in the NRS when all sonications were evaluated (β = -0.647, 95% CI -1.19 to -0.106, P = .0201), and in the NRS when all sonications were classified into 10 000 to 29 999 J (β = -1.83, 95% CI -3.17 to -0.485, P = .00889). SNB significantly reduced headache intensity during MRgFUS, especially that caused by sonication with a moderate-energy dose. These findings suggest that scalp nerves play a role in headache mechanisms during MRgFUS.

P682 A Retrospective Comparison of Different Treatment Modalities in Patients with Chronic Pouchitis

Abstract Background Chronic pouchitis affects ~30% of patients post total colectomy with ileal pouch anal anastomosis (IPAA) surgery. Treatment with anti-TNF, anti-integrin α4β7, anti-IL-12/23, or Crohn's disease exclusion diet (CDED), have shown promise in different studies. We aimed to compare the efficacy of these treatments in a real-world context and to detect factors that can aid in treatment choices. Methods A retrospective cohort study encompassing demographic, clinic, endoscopic, histologic and lab values of adult ulcerative colitis (UC) patients post-IPAA surgery with chronic pouchitis, treated with biologics or CDED at the Tel Aviv Medical Center. Data were collected at baseline, 12, 26, and 52 weeks of treatment. Primary outcomes were assessed using the modified Pouchitis Disease Activity Index (mPDAI). mPDAI response was defined as a reduction from baseline of ≥2 points, while mPDAI remission was defined as mPDAI response in addition to mPDAI score ≤4. Results Therapeutic interventions among 51 patients included CDED (n=10), vedolizumab (n=21), ustekinumab (n=7) and adalimumab (n=13) [Table 1]. At 12 and 26 weeks, overall mPDAI response rates were 52% and 48%, respectively, with no significant difference between groups. At 52 weeks, mPDAI response rates were significantly higher for ustekinumab and vedolizumab (60% and 55%, respectively) compared with adalimumab and CDED (27.3% and 0%, respectively), p=0.043. Fecal calprotectin reduction at week-26 was greatest for ustekinumab (93%), followed by vedolizumab (73%), adalimumab (55%), and CDED (-13%), p=0.003. Treatment persistence over 150 weeks was significantly higher for ustekinumab (100%) compared with adalimumab (46%), vedolizumab (33%), and CDED (20%), p&amp;lt;0.001 [Figure 1]. The predominant cause for treatment discontinuation was secondary loss of response (50%), followed by primary non-response and surgical complications (14.7% each), poor compliance (11.8%), side-effects (5.9%), and development of antibodies (2.9%). Patients without prior biologic or immunomodulator treatment for pouchitis had significantly higher mPDAI response rates at 12 weeks (90%, p=0.016 and 73.3%, p=0.03, respectively). Patients with surgical pouch complications showed a trend towards lower mPDAI-defined response rates at 12 weeks (25% vs. 64.7%; p = 0.064). Conclusion Ustekinumab and vedolizumab demonstrate higher likelihood of maintaining long-term clinical and endoscopic response, along with greater reduction in fecal calprotectin compared with adalimumab and CDED. Biologic and immunomodulator therapy-naïve patients achieved higher induction response rates.

Efficacy of Daratumumab-Based Regimens in Anti-CD38 Treatment-Naïve Relapsed/Refractory Multiple Myeloma with High-Risk Cytogenetics

Background: Daratumumab-based combination with proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs) have revolutionized the treatment outcomes of relapsed/refractory multiple myeloma (RRMM). Several daratumumab-based triplet combinations have been approved for the management of RRMM, but outcomes of daratumumab-based triplets in patients with high-risk cytogenetics RRMM (HC-RRMM) are not well described in the literature. This study aimed to evaluate the clinical outcome of daratumumab-based regimens in patients with HC-RRMM who are daratumumab-naïve. Methods: A retrospective review of 110 patients with HC-RRMM who received daratumumab-containing regimens from 6/2016 through 2/2023 at the University of Kansas Medical Center, in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC) was conducted. Daratumumab was combined with bortezomib/dexamethasone (DVd), carfilzomib/dexamethasone (DKd), and pomalidomide/dexamethasone (DPd) for treatment of RRMM. HC-RRMM was defined as patients with one or more cytogenetic abnormalities (on FISH panel) including -17/del(17p), t(4;14), t(14;16), t(14;20), or amplification of 1q. Responses to therapy including overall response rate (ORR), complete response or better (≥CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. Descriptive statistics were used to summarize patient and disease characteristics, along with efficacy outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier methods. Results: Of the 110 patients with HC-RRMM, the median age was 66 years (range 43-84), 83 (75%) were Caucasian, 60 (54%) had IgG isotype, 41 (37%) had revised international staging system (R-ISS) stage III disease, 35 (32%) had extramedullary disease (EMD), 57 (52%) patients had one high-risk cytogenetic (HC) abnormality, 49 (44%) had 2 HC abnormalities, while four (4%) had 3 HC abnormalities. The median number of previous lines of therapy was 2 (1-4). Eighty-eight patients (80%) were lenalidomide refractory, while 53 patients (48%) had double refractory disease to both a PI and IMiD treatment. A total of 19 (17%), 27 (25%), and 64 (58%) patients received DVd, DKd, and DPd, respectively. The overall response rate (ORR) for the entire patient population was 73%, 45% had VGPR or better, and 35% achieved ≥CR. Median follow-up was 28 months (12.07-53.57), the median OS was 28 months (95% CI 23.2 - 43.9) and PFS was 8.03 months (95% CI 5.8 - 12.2) for all treatment groups. The median PFS for 1 HC vs ³ 2 HC was 14.8 vs 4.57 months (HR 1.72, 95%CI 1.17-2.72 p = 0.006), respectively. Similarly, median OS for 1 HC vs ³ 2 HC was 43.93 vs 22.47 months (HR 1.87, 95%CI 1.15-3.05, p = 0.011), respectively. (Figure 1). On multivariate analysis, R-ISS stage III, -17/del(17p), and the presence of more than one HC abnormality were associated with poor OS. The most common cause for treatment discontinuation was progressive disease, accounting for 73% of patients in the whole cohort. As for each daratumumab-based triplet, discontinuation due progression occurred in 78%, 48%, and 83% in DVd, DKd, and DPd, respectively. Other causes of discontinuation included &amp;gt; grade 3 neuropathy, which occurred in 16% of patients receiving DVd, and cardiac events, which occurred in 11% of patients receiving DKd. Treatment-related mortality occurred in 2% of patients in the whole cohort. At the time of evaluation, 14 patients remain on treatment. Conclusion: Advanced stage R-ISS disease at diagnosis, presence of -17/del(17p), and 2 or more HC abnormalities were associated with poor prognosis reflected by worse PFS and OS in HC-RRMM treated with daratumumab-based therapies. A larger cohort or a prospective study in patients with HC-RRMM is needed to compare long-term outcomes between daratumumab-based therapies (DKd, DVd, and DPd).

The Efficacy and Safety of Zanubrutinib, Dexamethasone and or Not Cyclophosphamide Regimen in Symptomatic Waldenstrom Macroglobulinnemia

Background：Treatment of patients improved by Bruton tyrosine kinase (BTK) inhibitor in Waldenström macroglobulinemia (WM) ， but the efficacy of BTK-based regimen is not clear. A im: This single arm study evaluated the efficacy and safety of the com -bination of zanubrutinib, a novel, highly selective BTK inhibitor dexamethasone and or not cyclophosphamide in patients with WM. Methods：Symptomatic patients with WM were enrolled to the regimen of zanubrutinib, dexamethasone (ZD); patients' whose willingness were limit-cycle treatment received zanubrutinib, dexamethasone and cyclophosphamide (ZCD) *. The primary endpoint was objective response rate (ORR), progression-free survival (PFS). Key secondary endpoints included the proportion of patients achieving a complete or very good partial response (CR or VGPR), duration of response (DOR), Time to response (TOR), disease burden, and safety. The control group** were 30 matched patients treated by chemotherapy or immune-chemotherapy previously in Beijing Chaoyang Hospital. Results: A total of 30 Patients with WM were enrolled in this study median age 67(36-89); 76.7% males, 15 patients were untreated, others were treated patients. IPSS assessment grade1 26.7%; grade2 16.7%; grade3 56.6%. 80.0% (24/30) patients with MYD88L265P mutation 17.6% (3/17) patients with CXCR4 mutation. 29 patients received ≥1 dose of study treatment. Median follow-up of 9.2 months, median DOR and PFS were not reached; 95%of patients were progression-free at 6 months in 25 evaluable patients. ORR was 95% in those (24/25) received ZD/ZCD regimen more than 2 months. No patient achieved a CR. 33.3% of patients in ZD/ZCD group achieved a VGPR, time to VGPR within 3 months who received treatment after 6 months，a statistically significant difference with control group (0%, P = 0.001). Time to PR in ZD/ZCD group was 2 months, much faster than control group (11 months) (P = 0.021) by K-M analysis. 2 patients stopped the treatment after VGPR in ZCD group, 8 patients change to zanubrutinib single drug as maintenance in ZD/ZCD group, 3 patients discontinued treatment by disease progression or patients' willingness, others were still in this study. The study-safety profile was consistent with previous BTK inhibitor clinical trial data. 43.3% of patients had any grade AEs. In which, the most frequent grade &amp;lt;=2 AEs were hemorrhage(13.7% all grade 1), rash(6.7%), hyperglycemia (20%), infection(6.7%), nausea and vomiting (6.7%), hypogammaglobulinemia(3.3%), neutropenia(26.7%), thrombocytopenia (20.0%), Grade 3/4 AEs were neutropenia(3.3%), thrombocytopenia(6.7%), atrial fibrillation (3.3%), atrial fibrillation leading to treatment discontinuation. Other cause of treatment discontinuation is hyperglycemia, bowel obstruction by disease. C onclusion: These results demonstrate that zanubrutinib, dexamethasone and or not cyclophosphamide are quickly effective in the treatment of WM, with more deeper response and less toxicity, maybe treatment discontinued by combining with cyclophosphamide after deep remission. Comments *The regimen of ZD : Zanubrutinib 240mg d1-28, dexamethasone 20mg D1-4,15-18. Patients more than 75 years old, Zanubrutinib 160mg d1-28, dexamethasone 10mg D1-4,15-18. After 8 cycle, Zanubrutinib use as maintenance. The regimen of ZCD : Zanubrutinib 320mg d1-28, dexamethasone 20mg D1-4,15-18, cyclophosphamide 300mg, D1-4,15-18. Patients more than 75 years old, Zanubrutinib 160mg d1-28, dexamethasone 10mg D1-4,15-18, cyclophosphamide 200mg, D1-4,15-18. After 8 cycles, patients with VGPR remission receive Chlorambucil 6mg D1-4,15-18, dexamethasone 20mg D1-4,15-18, cyclophosphamide 300mg, D1-4,15-18 for 4cycles, others receive Zanubrutinib as maintenance. ** The control group: 30 treated patients with WM, median age 69.5(39-84); 60.0% males. IPSS Grade1 23.3%; Grade2 20.0%; Grade3 53.3%; Unknown 3.3%. 75% (9/12) patients with MYD88L265P mutation, 33.0% (1/3) patients with CXCR4 mutation. Treatment included chemotherapy (containing nitrogen mustard phenylbutyrate, fludarabine, cyclophosphamide), proteasome inhibitor regimens, rituximab regimens and immunomodulator regimens.

Final Analysis of the Daliah Trial: A Randomized Phase III Trial of Interferon-α Versus Hydroxyurea in Patients with MPN

Background: Hydroxyurea (HU) is the most commonly used first-line cytoreductive treatment option for patients with myeloproliferative neoplasms (MPN) worldwide. However, increasing evidence on the efficacy and safety of pegylated interferon-alpha2 (IFNα) is emerging, and optimal first-line treatment is to be established. Aims: To compare the efficacy and safety of HU vs. low-dose IFNα in patients with MPN over five years. Methods: DALIAH (NCT01387763) was a randomized phase III trial of HU vs. IFNα in newly diagnosed or untreated patients with MPN (essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic myelofibrosis (PreMF), and primary myelofibrosis (PMF)). Patients &amp;gt; age 60 were randomized (1:1:1) to HU, IFNα-2a, or IFNα-2b whereas patients ≤ age 60 were randomized to IFNα-2a or IFNα-2b. The primary outcome was the JAK2V617F molecular response (MR) rate at 18, 36, and 60 months per 2009 European LeukemiaNetwork (ELN) (ET, PV, PreMF) or 2005 European Myelofibrosis Network (EUMNET) (PMF) criteria. Secondary outcomes included the complete clinicohematologic response (CHR) rate at 12 months. The JAK2V617F allele burden was measured using quantitative polymerase chain reaction (qPCR) on peripheral blood (assay sensitivity: 0.1%). Primary and secondary outcomes were compared between groups (HU vs. IFNα or HU vs. IFNα &amp;gt; 60 years) using Fisher's exact test (categorical variables) or Wilcoxon rank-sum test (continuous variables). Paired comparisons (within groups) were made using Wilcoxon signed-rank test. Serial JAK2V617F measurements were compared by unadjusted mixed-effects linear regression analysis. Results: We included 203 patients (ET: 73 (36%), PV: 89 (44%), PreMF: 16 (8%), and PMF: 25 (12%)) in the modified intention-to-treat (ITT) population. Baseline characteristics were well balanced except for median age (HU: 68 years vs. IFNα: 59 years, p&amp;lt;0.0001) ( Table 1). The MR rate by ITT analysis was similar between HU and IFNα (18 months: 19% vs. 21%, p=1.00; 36 months: 19% vs. 26%, p=0.64; 60 months: 23% vs. 24%, p=1.00) (Figure 1A). However, the JAK2V617F allele burden was significantly lower in the IFNα group at month 36 and beyond (Figure 1B) and the absolute median (IQR) change in JAK2V617F allele burden (baseline to 60 months) was greater with IFNα (-20% (-9;-49) vs. -7% (3;-15), p=0.0053) (Figure 1C). Two patients (IFNα: n=2) were in complete molecular remission (undetectable JAK2V617F) at 60 months. The CHR rate by ITT analysis was higher with HU at 18 months (58% vs. 38%, p=0.03) but similar at all other time points (12 months: 50% vs. 36%, p=0.21; 60 months: 24% vs. 22%, p=0.83) ( Figure 1D). A post hoc subgroup analysis comparing HU with IFNα &amp;gt; age 60 showed comparable efficacy results. Among patients remaining on treatment (per-protocol analysis), the MR and CHR rates were superior in the IFNα group compared to the HU group at 36 months and beyond. The MR and CHR rates (HU vs. IFNα) by per-protocol analysis were: MR at 36 months: 23% vs. 56%, p=0.01; MR at 48 months: 27% vs. 59%, p=0.02; MR at 60 months: 35% vs. 67%, p=0.03; CHR at 36 months: 33% vs. 67%, p=0.002; CHR at 60 months: 38% vs. 62%, p=0.05. Overall treatment discontinuation at 60 months was 60% (HU: 37% vs. IFNα: 65%, p=0.0019). The most common cause of treatment discontinuation was adverse events (HU: 6/38 (16%); IFNα: 71/165 (43%)). Adverse events ≥ grade 3 occurred in 46% (HU: 58% vs. IFNα: 45%, p=0.15). Nineteen major thrombotic events were reported in 16 patients (HU: 4 events in 4 patients; IFNα&amp;gt;60: 12 events in 10 patients; IFNα≤60: 3 events in 2 patients), corresponding to an incidence rate of 2.6 per 100 person-years for HU and 3.4 per 100 person-years for IFNα (IFNα&amp;gt;60: 6.2; IFNα≤60: 1.2). None of the patients transformed into secondary acute myeloid leukemia. Five patients died during follow-up (HU: 2; IFNα: 3). Bone marrow histologic remission rates at 36 and 60 months will be presented at the meeting. Conclusion: ITT analysis detected no significant difference in the MR or CHR rates between HU and IFNα with long-term treatment (5 years) among patients with MPN, reflecting a higher treatment discontinuation rate in the IFNα group (65%). Thus, using the per-protocol principle, the MR and CHR rates were superior in the IFNα group at 36 months and beyond.

Real-world treatment outcomes and safety of natalizumab in Finnish multiple sclerosis patients.

The primary objective was to evaluate long-term treatment persistence and safety of natalizumab in Finnish multiple sclerosis patients. The secondary objectives were to assess patient characteristics, use of natalizumab-related safety protocol, and treatment persistence in patients with different anti-John Cunningham virus antibody statuses (John Cunningham virus status). All adult multiple sclerosis patients in the Finnish multiple sclerosis register who started natalizumab between 1/2006 and 12/2018 were included in this study and followed retrospectively until treatment discontinuation or end of follow-up (12/2019). In total, 850 patients were included. Median duration of natalizumab treatment was 7.8 years in John Cunningham virus negative (n = 229) and 2.1 years in John Cunningham virus positive patients (n = 115; p < 0.001). The most common cause for treatment discontinuation was John Cunningham virus positivity. After natalizumab discontinuation, patients who had a washout duration of less than 6 weeks had fewer relapses during the first 6 months (p = 0.012) and 12 months (p = 0.005) compared with patients who had a washout duration of over 6 weeks. During the median follow-up of 3.6 years, 76% of patients remained stable or improved on their Expanded Disability Status Scale. Treatment persistence was very high among John Cunningham virus negative patients. The study supports long-term effectiveness of natalizumab and a washout duration of less than 6 weeks after discontinuation.

Laparoscopic Inguinal Hernia Repair and Synchronous Peritoneal Dialysis Catheter Placement: A Single-Center Experience.

Background: Peritoneal dialysis (PD) is a common method for treating end-stage renal disease (ESRD). Occurrence of inguinal hernia before and during PD is considered to be the main cause of treatment discontinuation, failure, and conversion to hemodialysis. In this study, we present a single-center experience about laparoscopic inguinal hernia repair and synchronous PD catheter placement and evaluated the feasibility and outcomes. Methods: During May 2018 to May 2022, a total of 216 consecutive patients with ESRD underwent laparoscopic PD catheter placement. Among them, 41 patients (27.7%) with coexistent inguinal hernia were included in this study. Individual information, complications, recurrent and new-onset hernias, and catheter survival were retrospectively analyzed. Results: Forty-one patients underwent laparoscopic inguinal hernia repair and synchronous PD catheter placement, 9 patients had bilateral inguinal hernia, and another 32 patients had unilateral inguinal hernia. The mean age was 46.49 years (range, 28-72 years), including 39 males and 2 females. There was no recurrent hernia and only 1 patient (2.4%) developed incisional hernia (trocar site hernia) which required hernia repair and discontinuation of PD. No postoperative complications were observed, such as bleeding, infection, and dialysate leakage. After a median follow-up of 37 months (20-58 months), there were no deaths and 97.6% (40/41) catheters were still working. Conclusions: Laparoscopic hernia repair and synchronous PD catheter placement is an effective and safe treatment for ESRD patients with coexisting inguinal hernia in virtue of low postoperative complications and high catheter survival.

Effectiveness and safety of ustekinumab for the treatment of psoriasis; six years of clinical experience

BackgroundThis work aimed to investigate the long-term clinical experience with ustekinumab in cases with psoriasis.Materials and methodsThis retrospective cohort research group consisted of cases who presented to the dermatology outpatient clinics between January 2015 and January 2021, diagnosed with psoriasis, and were treated with ustekinumab. Data including gender, age, weight, disease duration, naïve and non-naïve status, psoriasis type, duration of medication, comorbidities, psoriasis area and severity index scores, the causes of treatment discontinuation, and previous treatments were retrospectively reviewed and analyzed.Results160 cases with psoriasis were treated with ustekinumab during the research period. Twenty-four patients were excluded. Among 136 cases, 84 (61.8%) were male and 52 (38.2%) were female. We determined 80.55% of the non-naïve cases responded to ustekinumab.ConclusionUstekinumab can be a suitable treatment option for non-naïve and resistant patients. Our data suggest the positive effect persists in cases with favorable responses to the first or second dose of ustekinumab. Also, we determined male cases gave more rapid and more robust responses than female cases, and patients were more willing about continuing the treatment.

RDPLF 2022 annual report: Profile of home hemodialysis patients in Belgium and Francel (synthetic raw results)

We present primary descriptive data in the form of tables and graphs for patients treated with home hemodialysis in France and French-speaking Belgium in 2022. These data were recorded in the database of the French-speaking Register of Peritoneal Dialysis and Home Hemodialysis (RDPLF).&#x0D; The average age of the patients is similar in both countries: 52.7 years in France and 54.7 years in Belgium. The percentage of patients with diabetes is 25.6% in Belgium and 18.5% in France.&#x0D; The majority of patients undergo daily hemodialysis 5 to 7 times per week.&#x0D; Of the patients, 11% have received peritoneal dialysis in the past. Of these, 23.5% transitioned to home hemodialysis less than 3 months after stopping peritoneal dialysis, while 23.6% transitioned after 2 years of center-based or self-administered hemodialysis.&#x0D; Practices differ between Belgium and France. In Belgium, a central catheter is used in 57.5% of cases, compared to 8.5% in France. For arteriovenous fistula puncture, the buttonhole technique is used in 91% of cases in Belgium and 47.8% of cases in France.&#x0D; In Belgium, 70% of patients dialyze independently, while in France, 71% of patients dialyze in the presence of a family member.&#x0D; The main cause of treatment discontinuation is transplantation (44% of technical dropout).

First-time adverse drug reactions, survival analysis, and the share of adverse drug reactions in treatment discontinuation in real-world rheumatoid arthritis patients: a comparison of first-time treatment with adalimumab and etanercept

ABSTRACT Background This study aims to compare nature and frequency of adverse drug reactions (ADRs), time to first ADR, drug survival, and the share of ADRs in treatment discontinuation of first-time treatment with adalimumab (ADA) and etanercept (ETN) in real-world RA patients. Research design and methods Retrospective, single-center cohort study including naïve patients treated between January 2003-April 2020. Time to first ADR and drug survival of first-time treatment were studied using Kaplan–Meier and Cox-regression models up to 10 years, with 2- and 5-year post-hoc sensitivity analysis. Nature and frequencies of first-time ADRs and causes of treatment discontinuation were assessed. Results In total, 416 patients (ADA: 255, ETN: 161, 4865 patient years) were included, of which 92 (22.1%) experienced ADR(s) (ADA: 59, 23.1%; ETN: 33, 20.4%). Adjusted for age, gender and concomitant conventional DMARD use, ADA was more likely to be discontinued than ETN up to 2-, 5- and 10-year follow-up (adjusted HRs 1.63; 1.62; 1.59 (all p<0.001)). ADRs were the second reason of treatment discontinuation (ADA 20.7%, ETN 21.4%). Conclusions Despite seemingly different nature and frequencies, ADRs are the second reason of treatment discontinuation for both bDMARDs. Furthermore, 2-, 5-, and 10-year drug survival is longer for ETN compared to ADA.

Imbalance in treatment discontinuation without progression between experimental and control arms among randomized trials in advanced breast cancer.

1110 Background: In Randomized Controlled Trials (RCT), treatment discontinuation (TD) can result in censoring. Imbalanced frequency of TD between arms could impact interpretation of results. Here, we quantify TD between the experimental and control arms among RCT supporting registration of drugs for advanced breast cancer. Methods: We identified RCT supporting US Food and Drug Administration's approval of drugs for advanced breast cancer between 2013 and 2023. We extracted data for the number of participants with TD for reasons other than disease progression (PD), death, or completion of treatment. Odds ratio (OR) for TD comparing experimental to control arms were determined for each trial. To assess progression-free survival (PFS) translation into an overall survival (OS) benefit, we calculated hazard ratio (HR) for PFS/OS. Then we assessed whether there was quantitative association between the OR for TD and the ratio of HR for PFS/OS. Quantitative significance was defined according to the criteria of Burnand. Results: Analysis included 22 RCT comprising 13853 participants and supporting approval for 18 distinct drugs. TD was reported in 2212 (16.0%) participants. Among these participants, the leading causes of TD were withdrawal of consent (27.8%), site termination (20.7%), adverse events (17.2%), and loss of follow-up (10.9%). There was a statistically significant imbalance in the experimental arm in 4 RCT (18%) (Table), which was observed for everolimus, ribociclib (with fulvestrant), alpelisib, and neratinib. The OR for TD showed quantitative, but not statistically significant negative association with the ratio of the HR for PFS/OS (Beta -0.393; p=0.18). Conclusions: TD without PD, death, or completion of treatment occurs in a substantial proportion of participants of several RCT supporting approval of drugs for advanced breast cancer. all the statistically significant imbalanced TD in the RCT were in experimental arms. Quantitative association between imbalanced TD and the ratio of HR for PFS/OS suggests imbalanced TD may impact ability to translate improvements in PFS to OS. Results of RCT with imbalance in TD should be interpreted cautiously. [Table: see text]

Outcomes among Hispanic metastatic breast cancer patients treated with alpelisib and fulvestrant: Single institution retrospective study.

e18836 Background: PIK3CA mutations are found in up to 40% of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancers (MBC). Alpelisib is an oral PIK3CA inhibitor approved in combination with fulvestrant. However, uptake has been limited due to toxicity concerns, most commonly hyperglycemia. Disparities regarding prevalence of diabetes exist among Hispanics (H). We previously reported the incidence and management of hyperglycemia in H MBC patients (pts) treated with alpelisib and fulvestrant at our institution. We now report outcomes and assess treatment patterns of H MBC pts compared to NH MBC pts. Methods: A retrospective chart review was performed to include pts with HR+ HER2- MBC with a documented PIK3CA mutation (detected by ctDNA or tissue) treated with alpelisib in combination with fulvestrant at Miami Cancer Institute from 2019-2022. Pts were identified using pharmacy records and the COTA real-world database (RWD). Cases were excluded where the start date was unclear, or treatment was given for a diagnosis other than breast cancer. Based on available data in the medical record, pts were categorized as H or NH. Descriptive statistical analysis was done using SAS version 9.4 (SAS Inc., Cary, NC). Results: Of 46 pts identified, 34 were included in the final analysis (17 H and 17 NH). The median age was 67 yrs. Median lines of therapy prior to the use of alpelisib and fulvestrant were 3.0 (3 H and 2 NH; p = 0.26). Almost all pts had prior treatment with a CDK4/6 inhibitor (94.1% H vs 100% NH; p = 0.31). Chemotherapy was the most common therapy used after alpelisib discontinuation (41.2% H vs 47.1% NH; p = 0.63). Disease progression was the main reason for discontinuation (64.7% H vs 70.6% NH; p = 0.32) followed by hyperglycemia (23.5% H vs 5.9% NH; p &gt; 0.05). Even though not statistically significant, the median days on treatment were shorter in H compared to NH (131d H vs 217d NH; p = 0.20). A clinical benefit rate of 35.3% was noted in H compared to 58.8% in NH (p = 0.17). Median survival time post receipt of alpelisib was shorter in H compared with NH (15 mo vs 29 mo; p = 0.06). Conclusions: We observed a trend towards shorter time on treatment and median survival time in H pts with HR+ MBC treated with alpelisib and fulvestrant compared to NH pts. This combination was used as second or third line of therapy, with most pts receiving chemotherapy at the time of progression. There was a trend towards less clinical benefit to alpelisib and fulvestrant in H pts vs NH pts. Given hyperglycemia was the second leading cause of treatment discontinuation among H, we hypothesize efforts to optimize glucose control in H will help maximize benefit to therapy and ultimately impact outcomes. Futher studies are warranted to better understand the different outcomes observed in H patients.

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study.

In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research.

Liver decompensation is a frequent cause of treatment discontinuation and prognostic factor in intermediate-advanced HCC

Introduction and ObjectivesWith the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. Patients and MethodsA multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). ResultsOverall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. ConclusionsThe complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.

Abstract P6-10-03: Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple-Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study

Abstract Background: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 mAb covalently linked to a highly potent topoisomerase I (Topo I) inhibitor payload via a stable, tumor selective, tetrapeptide-based cleavable linker. Dato-DXd has previously shown encouraging activity in heavily pretreated patients (pts) with metastatic TNBC (Krop, SABCS 2021). Here we report updated results from the TROPION-PanTumor01 study in pts with advanced/metastatic TNBC. Methods: TROPION-PanTumor01 (NCT03401385) is a phase 1, multicenter, open-label, 2-part dose-escalation/expansion study evaluating Dato-DXd in previously treated pts with solid tumors. Based on previous clinical and exposure-response results from pts with NSCLC, Dato-DXd 6 mg/kg IV Q3W is being evaluated in pts with advanced TNBC that relapsed/progressed on standard therapies; 2 pts received 8 mg/kg prior to selection of 6 mg/kg. The primary objectives were safety and tolerability. Tumor responses, including objective response rate (ORR; complete response [CR] + partial response [PR]) and disease control rate (DCR; CR + PR + stable disease [SD]), were assessed per RECIST v1.1 by blinded independent central review. Results: As of April 29, 2022, 44 pts received Dato-DXd (median follow-up, 16.6 mo [range, 13-22]) at the time of data cutoff. The primary cause of treatment discontinuation was disease progression (86%; PD or clinical progression), and 4 pts are still receiving therapy. Median age was 53 y (range, 32-82); 32% had de novo metastatic disease. Pts were heavily pretreated with a median of 3 (range, 1-10) prior regimens in the metastatic setting. Prior treatments included taxanes (91%), anthracyclines (75%), capecitabine (61%), platinum (52%), immunotherapy (43%), Topo I inhibitor–based ADC therapy (32%), and PARPi (18%). Treatment-emergent adverse events (TEAEs; all cause) occurred in 100% (any grade) and 50% (grade ≥3) of pts, respectively. Most common TEAEs (any grade, grade ≥3) were stomatitis (73%, 11%), nausea (66%, 2%), vomiting (39%, 5%), fatigue (34%, 7%), and alopecia (36%, 0%). One pt had grade 3 decreased neutrophil count; no cases of interstitial lung disease (ILD) or grade ≥3 diarrhea were observed. Serious TEAEs were reported in 9 pts (20%); no deaths associated with adverse events (AEs) were observed. Dose reductions occurred in 8 pts (18%) due to stomatitis (n=3), fatigue (n=2), dry eye (n=1), retinal exudates (n=1), and dysgeusia (n=1); 12 pts (27%) delayed treatment due to stomatitis (n=5), dry eye (n=1), keratitis (n=1), blurred vision (n=1), fatigue (n=1), bronchitis (n=1), skin infection (n=1), musculoskeletal chest pain (n=1), dysgeusia (n=1), chronic obstructive pulmonary disease (n=1), and dyspnea (n=1; &amp;gt;1 AE per pt). One pt (2%) discontinued treatment due to grade 1 pneumonitis (which was centrally adjudicated as not ILD). ORR in all pts was 32% (1 CR, 13 PRs), DCR was 80% (35/44), and clinical benefit rate (CR + PR + SD ≥6 mo) was 34% (15/44). Median duration of response was not yet reached; median progression-free survival (mPFS) was 4.3 mo (95% CI, 3.0-7.3), and median overall survival (mOS) was 12.9 mo (95% CI, 10.1-14.7). In the subset of pts without prior Topo I inhibitor–based ADC therapy and with measurable disease at baseline, ORR was 44% (12/27). Among all pts without prior Topo I inhibitor–based ADC therapy (n=30), mPFS was 7.3 mo (95% CI, 3.0-NE), and mOS was 14.3 mo (95% CI, 10.5-NE). Conclusions: Dato-DXd continues to demonstrate encouraging and durable antitumor activity, along with a manageable safety profile, in heavily pretreated pts with metastatic TNBC. Based on these findings, the phase 3 randomized TROPION-Breast02 (NCT05374512) trial comparing Dato-DXd vs chemotherapy as 1L therapy for pts with metastatic TNBC is currently underway. Citation Format: Aditya Bardia, Ian Krop, Funda Meric-Bernstam, Anthony W. Tolcher, Toru Mukohara, Aaron Lisberg, Toshio Shimizu, Erika Hamilton, Alexander I. Spira, Kyriakos P. Papadopoulos, Jonathan Greenberg, Wen Gu, Fumiaki Kobayashi, Hong Zebger-Gong, Yui Kawasaki, Rie Wong, Takahiro Kogawa. Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple-Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-03.

Abstract PD13-08: PD13-08 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor–Positive/HER2–Negative Breast Cancer (BC)

Abstract Background: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to a highly potent topoisomerase I (Topo I) inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. Dato-DXd demonstrated compelling single-agent antitumor activity in heavily pretreated patients (pts) with metastatic triple-negative BC (Krop, SABCS 2021). This is the first report of results from the TROPION-PanTumor01 study in pts with unresectable or metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−; including HER2-low and HER2-zero) BC. Methods: TROPION-PanTumor01 (NCT03401385) is a phase 1, multicenter, open-label, 2-part dose-escalation/expansion study evaluating Dato-DXd in previously treated pts with solid tumors. Based on previous clinical findings and exposure-response results from pts with NSCLC, Dato-DXd 6 mg/kg IV Q3W is being evaluated in pts with unresectable or metastatic HR+/HER2− BC that progressed on standard therapies. The primary objectives were safety and tolerability. Tumor responses, including ORR (complete response [CR] + partial response [PR]) and DCR (CR + PR + stable disease [SD]), were assessed per RECIST version 1.1 by blinded independent central review. Results: As of the April 29, 2022, data cutoff, 41 pts had received Dato-DXd (median follow-up, 10.9 mo [range, 7-13]); 9 pts were ongoing. The primary cause of treatment discontinuation was disease progression (63%; progressive disease [PD] or clinical progression). Median age was 57 y (range, 33-75); 54% had de novo metastatic disease. Pts were heavily pretreated (Table) with a median of 5 (range, 3-10) prior regimens in the advanced setting; 95% had prior CDK4/6i (adjuvant/metastatic). Median time from initial treatment for metastatic disease to the first dose of Dato-DXd was 42.7 mo (range, 10.2-131.1). Treatment-emergent adverse events (TEAEs; all cause) were observed in 98% (any grade) and 41% (grade ≥3) of pts. Most common TEAEs (any grade, grade ≥3) were stomatitis (80%, 10%), nausea (56%, 0%), fatigue (46%, 2%), and alopecia (37%, 0%). Serious TEAEs were observed in 6 pts (15%); 1 pt died due to dyspnea, which was not considered to be treatment related. Dose reductions occurred in 5 pts due to stomatitis (n=3), fatigue (n=2), keratitis (n=1), and decreased appetite (n=1) (&amp;gt;1 AE per pt); 14 pts had treatment delayed due to stomatitis (n=8), retinopathy (n=1), dysphagia (n=1), fatigue (n=1), malaise (n=1), COVID-19 (n=1), cellulitis (n=1), urinary tract infection (n=1), decreased lymphocyte count (n=1), and nasal congestion (n=1; &amp;gt;1 AE per pt). Three pts discontinued treatment due to keratitis (n=1) and pneumonitis (n=2); 1 case of pneumonitis was adjudicated as grade 2 drug-related interstitial lung disease. The ORR was 29% (11 confirmed PRs; 1 pending confirmation), the DCR was 85% (35/41), and the clinical benefit rate (CR + PR + SD ≥6 mo) was 41% (17/41). Conclusions: Dato-DXd demonstrated a manageable safety profile and encouraging antitumor activity, with high disease control in heavily pretreated pts, the majority having received prior CDK4/6i. Based on these findings, the TROPION-Breast01 (NCT05104866) randomized phase 3 study comparing 2L+ Dato-DXd vs investigator’s choice chemotherapy is currently enrolling pts with HR+/HER2− BC. Prior Therapies in the Adjuvant or Metastatic Setting Citation Format: Funda Meric-Bernstam, Ian Krop, Dejan Juric, Takahiro Kogawa, Erika Hamilton, Alexander I. Spira, Toru Mukohara, Takuya Tsunoda, Senthil Damodaran, Jonathan Greenberg, Wen Gu, Fumiaki Kobayashi, Hong Zebger-Gong, Yui Kawasaki, Rie Wong, Aditya Bardia. PD13-08 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor–Positive/HER2–Negative Breast Cancer (BC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD13-08.