Primary Reason For Discontinuation Research Articles

Long-term drug survival of risankizumab in psoriasis: insights from a real-life multicenter study on hard-to-treat areas.

Psoriasis, a chronic inflammatory condition, often presents challenges in treatment, particularly in areas such as nails, palms/soles, scalp/face, and genitalia. Monoclonal antibodies (mAb) like risankizumab targeting interleukin-23 (IL-23) have emerged as promising treatments, yet data on long-term efficacy remain limited. This multicenter retrospective study aimed to evaluate the drug survival at 12 and 36 months of 191 psoriasis patients treated with risankizumab, focusing on critical areas. Patients, previously unresponsive to first-line therapies, were treated according to Italian Guidelines. Survival analysis revealed a 97.6% one-year and 95% three-year drug survival rate. Secondary ineffectiveness was the primary reason for discontinuation, particularly in palmoplantar involvement cases. Factors such as BMI, gender, age, disease duration, baseline severity, and previous biologic exposure did not significantly impact drug survival, except for palmoplantar psoriasis (HR 4.72). Risankizumab demonstrated prolonged response with low treatment switch requirements, especially notable in challenging areas. Understanding such factors can aid in optimizing therapeutic approaches for improved patient care and long-term outcomes in managing psoriasis. Further research is warranted to refine treatment strategies in difficult-to-treat areas.

Abstract PS07-04: Improved uptake and adherence to prevention medication with use of baby tamoxifen in patients at high risk for breast cancer

Abstract Background: Women at increased risk for breast cancer (BC) may benefit from taking prevention medication (PM) with tamoxifen (tam). Historical uptake to PMs for women who qualify has been low. Recent studies have shown baby tam (5mg/day) to have similar efficacy to standard dosing (20mg/day) with lower risk for adverse events (AEs) in women with DCIS or high risk intraepithelial lesions. Herein, we aimed to evaluate uptake, adherence, and tolerability of baby tam in women at increased risk for BC and those with DCIS. Methods: Women seen at the Mayo Clinic Breast Center in Minnesota or Florida who qualified for PM due to DCIS, high risk intraepithelial lesions (IELs) including LCIS and/or AH, or with increased risk based on validated BRCAT or IBIS model calculation (BCRAT 5 year risk ≥ 3% or IBIS 10 year risk ≥ 8%) were offered participation. All women received consultation with a breast specialist for discussion of PM rationale, benefits, side effects, and risks. Patients received baseline survey to assess understanding of their risk and role for PM and then 1 year follow-up survey to assess adherence and tolerability. Results: 41 patients consented for participation and 31 of those completed follow-up at 1 year.Median age of enrollment was 49 years. After initial consultation, 90% (n=37) reported good or complete understanding of BC risk. Of the 31 patients included in 1 year follow-up, 5 patients had DCIS, 13 had high-risk IELs, and 13 qualified based on BCRAT/IBIS calculation. Seventy-four percent (n= 23) of patients reported they took baby tam after consultation. No differences in age (p=0.89), education (p=0.13), or menopause status (p=0.11) between those who did and did not take medication were seen. Those who initiated baby tam were more likely to have DCIS or high risk IEL compared to those who did not (p < 0.001). Seventy-eight percent (n=18) of those who initiated baby tam were still taking medication at 1 year follow-up. Of patients who discontinued baby tam, all cited side effects as primary reason for discontinuation, with hot flashes (n=2), night sweats (n=2), and fatigue (n=2) being most common. Patients who continued medication had higher estimated BC risk compared to those who discontinued baby tam (IBIS 10 yr risk 12.7% vs 7.6%, p = 0.027). Patients with DCIS or high risk IEL were more likely to continue medication at 1 year compared to those patients who qualified for PM based on calculated BCRAT/IBIS score (p=0.05). Only 1 patient with DCIS and 1 patient with high-risk IEL discontinued baby tam at 1 year. Conclusions: Uptake to baby tam after informed discussion in patients who qualify is high, especially in those patients with high risk IELs or DCIS. Adherence and tolerability at 1 year follow-up is improved compared with traditional dosing of tam. Qualifying criteria for patients who did and did not take baby tamoxifen after informed consultation with breast specialist Citation Format: Lauren Cornell, Sandhya Pruthi, Karthik Ghosh, Klassen Christine, Pooja Advani. Improved uptake and adherence to prevention medication with use of baby tamoxifen in patients at high risk for breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS07-04.

A retrospective analysis of ibrutinib outcomes in relapsed or refractory mantle cell lymphoma.

While treatment strategies for mantle cell lymphoma (MCL) have evolved, patients often experience disease progression and require additional treatment therapies. Ibrutinib presents a promising option for relapsed or refractory MCL (RR-MCL). This study investigated real-world treatment outcomes of ibrutinib in patients with RR-MCL. A single-center retrospective analysis investigated clinical characteristics and survival outcomes of patients with RR-MCL, treated with ibrutinib. Forty-two patients were included, with 16 received rituximab and bendamustine, and 26 receiving anthracycline-based regimens as front-line treatment. During a median follow-up of 46.0 months, the response rate to ibrutinib was 69%, with 12 CRs and 8 partial responses. Disease progression (54.8%) and adverse events (11.9%) were the primary reasons for discontinuation. Median progression-free survival (PFS) and overall survival (OS) were approximately 16.4 and 50.1 months, respectively. Patients older than 70 years (P=0.044 and P=0.006), those with splenomegaly (P=0.022 and P=0.006), and those with a high-risk simplified Mantle Cell Lymphoma International Prognostic Index (sMIPI) (P＜0.001 and P＜0.001) exhibited siginificantly inferior PFS and OS. Notably, patients with a high-risk sMIPI relapsed earlier. Post-ibrutinib treatment yilded an OS of 12.2 months, while clinical trial participants demonstrated superior survival compared to those receiving chemotherapy alone. This study underscores the importance of considering patient characteristics before administering ibrutinib as salvage therapy. Early relapse was associated with poor outcomes, highlighting the need for novel therapeutic strategies.

Baseline characteristics may impact treatment duration of cabazitaxel in patients with mCRPC: a subanalysis of data from a post-marketing surveillance.

Cabazitaxel has demonstrated improvements in overall survival among patients with metastatic castration-resistant prostate cancer (mCRPC) in the pivotal comparison clinical trials TROPIC, PROSELICA and CARD. However, these trials include mCRPC patients with similar characteristics, and there are limited data on how baseline characteristics affect treatment discontinuation in the patient population. To assess individual factors that may impact the discontinuation rate of cabazitaxel treatment, we conducted a post hoc analysis of data from a nationwide all-case, post-marketing surveillance of cabazitaxel in Japan. Patients were grouped according to the number of cabazitaxel treatment cycles received (1-2 and≥3cycles). Predictive factors were identified through multivariate logistic regression analysis. Across 660 patients with metastatic castration-resistant prostate cancer, 70.2% received ≥3cycles of cabazitaxel treatment. Those receiving 1-2cycles of cabazitaxel had a greater proportion of patients with poorer Eastern Cooperative Oncology Group Performance Status, presence of lung and liver metastases, higher prostate-specific antigen level and prior radiation therapy at baseline. Regardless of the number of cabazitaxel cycles received, the primary reason for discontinuation was progression of disease rather than adverse events. Compared with those receiving 1-2cycles, a lower proportion of patients receiving 3-10 and≥11cycles of cabazitaxel treatment experienced adverse events. Multivariate analysis showed a significant association between early discontinuation and presence of liver lesions, poorer Eastern Cooperative Oncology Group Performance Status and higher prostate-specific antigen level at baseline. Post-marketing surveillance data suggest physicians should individualize cabazitaxel treatment based on certain patient characteristics at baseline.

Long-Term Safety and Effectiveness of Delayed-release Dimethyl Fumarate in Multiple Sclerosis Patients Treated in Routine Medical Practice, an updated analysis of the ESTEEM Study (P7-3.009)

Long-Term Safety and Effectiveness of Delayed-release Dimethyl Fumarate in Multiple Sclerosis Patients Treated in Routine Medical Practice, an updated analysis of the ESTEEM Study (P7-3.009)

Compliance and Persistence With Ofatumumab Treatment in Patients With Relapsing Multiple Sclerosis in Clinical Trials for Up to 4 Years (P8-3.002)

Compliance and Persistence With Ofatumumab Treatment in Patients With Relapsing Multiple Sclerosis in Clinical Trials for Up to 4 Years (P8-3.002)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Improving the Acceptance Rate of Centchroman As a Postpartum Contraceptive Through a Quality Improvement Initiative.

BackgroundThe unmet need for contraception is two-pronged: a spacing method and a permanent method. Centchroman, a non-hormonal, non-steroidal oral contraceptive, is suitable for both of these purposes. The Government of India provides it free of cost under the name "Chhaya", but its current acceptance rates are lower than expected. We aimed to increase the acceptance rates of centchroman as a postpartum contraceptive through a quality improvement (QI) approach conducted over eight months at a tertiary care hospital in North India.Materials and MethodsThis QI study was done in three phases: a pre-intervention phase of over eight weeks to assess the baseline acceptance and prevalence rates of centchroman use; an intervention phase of over 12 weeks involving three Plan-Do-Study-Act (PDSA) cycles to increase the awareness and acceptance of centchroman among the target population using visual aids and counselling by the nursing staff and resident doctors, respectively; and a post-intervention phase of over 12 weeks to assess the acceptance and continuation rates of Chhaya.ResultsThe acceptance rates for centchroman increased from a baseline of 2.9% to 15.3%, 56.3%, and 78.2% after the first, second, and third PDSA cycles, respectively. On follow-up, continuation rates were 96.7%, 89.5%, and 78.6% at one, three, and six months, respectively. The majority of women reported only minor side effects, with the primary reason for discontinuation being a preference for intrauterine devices or medroxyprogesterone acetate injections over Chhaya. ConclusionThe postpartum period provides an important window of opportunity to counsel women for contraception. Despite an enviable safety profile and dosing schedule, centchroman remains largely under-utilized. Increasing awareness among women as well as health care workers may improve the acceptance of centchroman and help reduce the burden of untimely and unwanted conceptions.

High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial

IntroductionPatients with life-threatening advanced non-small cell lung cancer (NSCLC) who harbor an exon 20 deletion and/or insertion mutation (EGFRex20 + ) have limited effective treatment options. The high dose 3rd generation tyrosine kinase inhibitor (TKI) osimertinib shows promising in vitro activity in EGFRex20 + NSCLC tumors. MethodsThe POSITION20 is a single arm phase II, multicenter study investigating 160 mg osimertinib in patients with EGFRex20+, T790M negative NSCLC. We allowed patients to be treatment naïve and to have asymptomatic brain metastases. The primary endpoint was overall response rate (ORR). Secondary outcomes were duration of response (DoR), progression free survival (PFS), overall survival (OS), and treatment related adverse events (trAEs). ResultsFrom June 2018 to October 2021, 25 patients were enrolled across five centers in the Netherlands. The median age was 70 years (range, 47–87), 20 patients (80%) were women, and the median number of previous lines of therapy was 1 (range, 0–3). The exon 20 mutations were clustered between A763 and L777. The most common exon 20 mutations were p.(N771_H773dup) (n = 3) and p.(A767_V769dup) (n = 3). The ORR was 28% (95% CI, 12–49%), including seven partial responses, with a median DoR of 5.3 months (range, 2.7–27.6). The median PFS was 6.8 months (95% CI, 4.6–9.1) and the median OS was 15.2 months (95% CI, 14.3–16.0). The most common trAEs were diarrhea (72%), dry skin (44%), and fatigue (44%). The primary reason for discontinuation was progressive disease in 14 patients (56%). ConclusionThe POSITION20 study showed modest antitumor activity in patients with EGFRex20 + NSCLC treated with 160 mg osimertinib, with a confirmed ORR of 28% and acceptable toxicity.

LITESPARK-004 (MK-6482-004) phase 2 study of belzutifan, an oral hypoxia-inducible factor 2α inhibitor (HIF-2α), for von Hippel-Lindau (VHL) disease: Update with more than two years of follow-up data.

4546 Background: VHL disease is associated with malignant or benign tumors, including renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNETs), and hemangioblastomas. Alterations in the VHL gene cause aberrant stabilization and accumulation of HIF-2α, leading to activation of genes associated with tumor growth. Antitumor activity observed in the ongoing open-label phase 2 study, LITESPARK-004 (NCT03401788), led to the approval of belzutifan for the treatment of patients (pts) with VHL disease who require therapy for associated RCC, CNS hemangioblastomas, or pNETs not requiring immediate surgery. Updated results are presented after > 2 years of follow-up. Methods: Pts (≥18 years) with germline VHL alterations, ≥1 measurable nonmetastatic RCC tumor, no tumor of > 3 cm that necessitated immediate surgery, no prior anticancer systemic treatment, and an ECOG PS score of 0 or 1 received oral belzutifan 120 mg once daily until disease progression, unacceptable toxicity, or pt withdrawal. The primary end point was objective response rate (ORR) in VHL disease–associated RCC per RECIST v1.1 by independent central review (ICR). Secondary end points were safety, ORR in non-RCC neoplasms, and duration of response (DOR) in renal and nonrenal neoplasms, per RECIST v1.1 by ICR. Results: Of 61 pts, 50 were on treatment as of July 15, 2021; the primary reasons for discontinuation were disease progression in RCC neoplasms (n = 4) and pt decision to withdraw (n = 4). Twenty pts (33%) had ≥1 pNET and 50 (82%) had ≥1 CNS hemangioblastoma evaluable by ICR at baseline. At baseline, 97% of pts (n = 59) had prior VHL-related surgery; 38 pts had ≥1 VHL-related surgery within 3 years before starting belzutifan. Median time from first dose to database cutoff date was 29.3 mo (range, 27.6-37.5). ORR in RCC was 59% (n = 36), with 2 CRs (3%) and 34 PRs (56%). Median DOR was not reached (range, 8.3+ to 27.6+ mo). ORR in CNS hemangioblastomas was 38% (n = 19; 3 CRs; 16 PRs); median DOR was not reached (range, 3.7+ to 28.0+ mo). ORR in pNETS was 90% (n = 18; 3 CRs; 15 PRs); median DOR was not reached (range, 11.0+ to 31.0+ mo). Three pts (5%) underwent VHL-related surgeries after starting belzutifan. Grade 3 treatment-related adverse events (TRAEs) were reported in 10 pts (16%); the most common was anemia (n = 6 [10%]). No pt had a grade 4 or 5 TRAE. Two pts (3%) stopped treatment because of TRAEs (grade 1 dizziness and grade 2 intracranial hemorrhage). Conclusions: After a median follow-up of 29.3 mo, belzutifan continued to show antitumor activity in VHL disease–related neoplasms, including RCC, pNETs, and CNS hemangioblastomas, whereas the safety profile remained consistent with that of previous reports. These results support the use of belzutifan as a systemic treatment for VHL disease. Clinical trial information: NCT03401788.

Phase 1 LITESPARK-001 (MK-6482-001) study of belzutifan in advanced solid tumors: Update of the clear cell renal cell carcinoma (ccRCC) cohort with more than 3 years of total follow-up.

4509 Background: Hypoxia-inducible factor 2α (HIF-2α) is a key oncogenic driver in RCC. Antitumor activity of the HIF-2α inhibitor belzutifan has been observed in RCC and is approved for treatment in patients (pts) with VHL disease who require therapy for associated RCC, CNS hemangioblastomas, or pNETs not requiring immediate surgery. Previous data from the phase 1 LITESPARK-001 trial (NCT02974738) designed to evaluate belzutifan in heavily pretreated RCC showed durable antitumor activity and an acceptable safety profile. After more than 3 years of follow-up for pts with ccRCC still receiving treatment, updated data are presented. Methods: Pts enrolled in the ccRCC cohort were previously treated with ≥1 therapy, had RECIST-measurable disease, ECOG PS score of 0 or 1, adequate organ function, and life expectancy of ≥6 months. Pts received oral belzutifan 120 mg once daily. The primary end point was safety. Secondary end points were ORR, DCR (CR + PR + SD), PFS, and DOR per RECIST v1.1 by investigator. The data cutoff date was July 15, 2021. Results: Of 55 pts enrolled in the ccRCC cohort, 9 (16%) remain on treatment as of the data cutoff date of July 15, 2021; the primary reason for discontinuation was progressive disease (n = 34; 62%). Pts received a median of 3 prior therapies (range, 1-9); 39 (71%) received prior VEGF and immunotherapy. Pts were followed while on treatment and for 30 days after the last dose for a median of 41.2 months (range, 38.2-47.7). Twenty-two pts (40%) experienced grade 3 TRAEs. The most common (≥10%) grade 3 TRAEs were anemia (n = 13; 24%) and hypoxia (n = 7; 13%). There were no grade 4 or 5 TRAEs. ORR was 25%, with 1 confirmed CR (2%) and 13 PRs (24%); DCR was 80%. Median DOR was not reached (range, 3.1+ to 37.9+ months); 8 of 14 responding pts (57%) remain in response as of the data cutoff date. Per IMDC risk, 4 of 13 pts with favorable risk achieved response (ORR = 31%; all PRs) and 10 of 42 pts with intermediate/poor risk achieved response (ORR = 24%; 1 CR, 9 PRs). DCR was 92% for pts with favorable risk and 76% for pts with intermediate/poor risk. For pts who received prior VEGF and immunotherapy, 8 of 39 pts achieved response (ORR = 21%; 1 CR; 7 PR); DCR was 74%. For the 16 pts who did not receive prior VEGF/immunotherapy, 6 achieved response (ORR = 38%; all PRs); DCR was 94%. Median PFS for the total cohort was 14.5 months (95% CI, 7.3-22.1); PFS rate at 156 weeks (̃36 months) was 34%. Conclusions: As seen after a median follow-up of > 3 years for pts still receiving treatment, belzutifan monotherapy continued to show a high rate of disease control and durable responses in previously treated pts with advanced ccRCC. Belzutifan exhibited a favorable safety profile, and no new safety signals were observed. In several phase 3 studies, belzutifan is being evaluated as monotherapy and combined therapy for ccRCC. Clinical trial information: NCT02974738.

Treatment of alpelisib induced hyperglycemia with sodium-glucose cotransporter-2 inhibitors: A single institution experience.

e13041 Background: PIK3CA mutations occur in about 40% of patients with HR+/HER2- breast cancer. The phase III SOLAR-1 trial demonstrated prolonged progression-free survival with alpelisib and fulvestrant compared to fulvestrant alone among patients with HR+/HER2-/ PIK3CA mutant advanced breast cancer previously treated with endocrine therapy. Hyperglycemia was seen in 64% of patients treated with alpelisib and fulvestrant and was treated with metformin. Inhibition of PI3Kα leads to an on-target effect of hyperglycemia and a secondary hyperinsulinemia. This rebound hyperinsulinemia may lead to escape PI3K pathway activation in breast cancer progression via the insulin and IGF1pathways. Concurrent administration of SGLT2 inhibitors may abrogate the PI3K pathway activation effect and delay disease progression. This study reports time on treatment with alpelisib and PFS among patients who received an SGLT2 inhibitor with alpelisib. Methods: A retrospective review of all metastatic breast cancer patients treated with alpelisib was completed from 8/2019 to 5/2021 at the Saint Luke’s Koontz Center for Advanced Breast Cancer. Results: This review included 22 female patients, 11 received an SGLT2 inhibitor for treatment related hyperglycemia (A+SGLT group) and 11 who received metformin/other diabetic agents (A group). Baseline characteristics were not significantly different between the two groups: median age 63, BMI of 29.1, hemoglobin A1C of 6.3 and fasting blood glucose of 119.1mg/dl. PIK3CA mutations included H1047X (40.9%), E545X (31.8%), E542K (13.6%), other (13.6%). The median number of prior treatments for MBC was 3 (range 1-5). Prior treatments included aromatase inhibitors: 100%, fulvestrant: 77%, CDK 4/6 inhibitors: 82%, everolimus: 32% and chemotherapy: 68%. Hyperglycemia grade 2+ was seen in 72.7% of patients. There were no significant differences between the two groups for emergency room visits, hospitalizations, or endocrinology referrals related to hyperglycemia. Median time to initiation of an SGLT2 inhibitor was 13 days following the first dose of alpelisib. PFS was longer in the A+SGLT compared with the A group with a median time to progression of 6.1 months and 3.9 months respectively (HR 0.51; 95% CI 0.16 to 1.63; p = 0.39). Time on treatment was significantly longer for A+SGLT group compared with the A group, with a median time on treatment of 5.8 months, compared with 3.0 months (HR 0.32; 95% CI 0.11 to 0.92; p = 0.03). The primary reason for discontinuation of alpelisb was disease progression in 73%, with no statistically significant difference in the reason for discontinuation between the groups. Conclusions: This study supports a potential clinical benefit of an SGLT inhibitor along with alpelisib in allowing for a longer time on treatment, without significant adverse events. It also suggests a possible favorable impact on PFS for the combination.

PD35-07 ANALYSIS OF DISCONTINUATION RATES AND CAUSES OF EARLY DISCONTINUATION OF NOVEL ORAL HORMONE THERAPY IN MEN WITH ADVANCED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD35-07 ANALYSIS OF DISCONTINUATION RATES AND CAUSES OF EARLY DISCONTINUATION OF NOVEL ORAL HORMONE THERAPY IN MEN WITH ADVANCED PROSTATE CANCER David Gangwish, Bernadette Zwaans, Paul Miriani, Wesley Dejoie, Andrina Ajo, Connor Ervin, Jeff Sarazin, and Jason Hafron David GangwishDavid Gangwish More articles by this author , Bernadette ZwaansBernadette Zwaans More articles by this author , Paul MirianiPaul Miriani More articles by this author , Wesley DejoieWesley Dejoie More articles by this author , Andrina AjoAndrina Ajo More articles by this author , Connor ErvinConnor Ervin More articles by this author , Jeff SarazinJeff Sarazin More articles by this author , and Jason HafronJason Hafron More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002593.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is the second most common cause of cancer-specific death in US men. Novel oral hormone therapy (NHT) significantly prolongs survival and maintains quality of life in advanced PCa patients. Despite known benefits, these medications are commonly discontinued. The study evaluated the prevalence of early discontinuation of NHT, the determinants of early discontinuation and the effect of changing NHT on duration of treatment. METHODS: A retrospective cohort study of 333 patients with advanced PCa who started a NHT in a single community urology practice in the United States between February 2016 and July 2020 were evaluated. NHT medication, start date of treatment, reason for discontinuation, and discontinuation date were collected. Additional data included demographics, stage of PCa, PSA at time of NHT initiation, Gleason score, and prior PCa treatments. The cohort was divided into 2 subgroups, those did not change medication (Group A) and those that did change to a different NHT (Group B). Student’s t-test, Chi-square test, and Kaplan-Meier survival analysis were carried out to determine significant differences between groups (SPSS). RESULTS: At one year 28.8% of patient’s had early discontinuation of NHT. The most common reasons for discontinuation were side effects and death at 34.4% each. Group A (282 patients) and Group B (51 patients) discontinued treatment at a rate of 31%, 88%, respectively. Primary reasons for discontinuation in group A versus group B was due to side effects (36% vs 47%) or cancer progression (34% vs 49%). More patients in group B were deceased than in group A (58.8% vs 29.4%). Of those that discontinued, patients remained on NHT for an average of 382 days in group A versus 593 days in group B (Figure 1, Kaplan-Meier analysis p = 0.003). In group B, patients on average discontinued first NHT after 330 days and continued secondary NHT for an additional 263 days. CONCLUSIONS: Side effects and cancer progression were the main reasons for discontinuing NHT treatment. Providing patients with alternative NHT significantly increases the duration of treatment. It is important for clinicians to understand the causes of early discontinuation to develop strategies to maximize duration of therapy for management of advanced PCa. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e629 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Gangwish More articles by this author Bernadette Zwaans More articles by this author Paul Miriani More articles by this author Wesley Dejoie More articles by this author Andrina Ajo More articles by this author Connor Ervin More articles by this author Jeff Sarazin More articles by this author Jason Hafron More articles by this author Expand All Advertisement PDF DownloadLoading ...

Efficacy and safety of nivolumab plus ipilimumab (N+I) versus sunitinib (S) for first-line treatment of patients with advanced sarcomatoid renal cell carcinoma (sRCC) in the phase 3 CheckMate 214 trial with extended 5-year minimum follow-up.

352 Background: sRCC is an aggressive histologic growth pattern in RCC with a poor prognosis and limited therapeutic options. First-line N+I provided efficacy benefits over S in patients (pts) with sRCC and intermediate/poor (I/P)-risk disease at 42 months follow-up. Here, we report an exploratory post hoc analysis of N+I vs S in pts with I/P-risk and sRCC with long-term follow-up of 5 years. Methods: Pts with clear cell advanced RCC were randomized 1:1 to N 3 mg/kg plus I 1 mg/kg every 3 weeks × 4, then N 3 mg/kg every 2 weeks vs S 50 mg once daily (4 weeks; 6-week cycles). Pts with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology. Outcomes in pts with sRCC were not prespecified. Endpoints in pts with sRCC and IMDC I/P risk included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Outcomes were also assessed per baseline tumor PD-L1 expression level (≥1% vs <1%). Safety outcomes used descriptive statistics. Results: Of 1096 randomized pts in CheckMate 214, 139 I/P-risk pts with sRCC were identified (N+I, n = 74; S, n = 65). Of all treated pts, 9 of 73 (12%) in the N+I arm vs zero of 65 in the S arm remained on treatment. The primary reason for discontinuation was disease progression (N+I, 37%; S, 71%). OS continued to favor N+I vs S (HR 0.46 [95% CI 0.29–0.71]; P = 0.0004; table). PFS benefit with N+I vs S was similarly maintained (HR 0.50 [95% CI 0.32–0.80; P = 0.0036]). Additionally, ORR was higher (61% vs 23%; P < 0.0001), median duration of response was longer (NR vs 25 months), and more pts had complete responses (23% vs 6%) with N+I vs S, respectively. Efficacy was better with N+I vs S regardless of PD-L1 expression, yet the degree of OS, PFS, and ORR benefits with N+I was greater for pts with PD-L1 ≥ 1% (Table). No new safety signals emerged in either arm. Conclusions: N+I showed clinically meaningful benefits in long-term OS, PFS, and the frequency and depth of response vs S in previously untreated pts with sRCC and I/P-risk disease, supporting N+I as a preferred first-line therapy in this population. Clinical trial information: NCT02231749. [Table: see text]

A multicenter real-world study reviewing systemic anticancer treatment choices and drop off rates between treatment lines for metastatic renal cell carcinoma in the United Kingdom: In the immunotherapy era.

358 Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over the last few years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. A previous real world study in the UK had demonstrated a significant attrition rate between each line of therapy suggesting less than half of patients who received first line SACT then received second line therapy and less than a fifth of first line SACT patients reach third line. Methods: We conducted a retrospective analysis of all patients treated between January 2018 and end of June 2021 to see if advancement in treatment options had impacted on the drop-off rates. Data was collected from 5 UK sites. Patients were identified from electronic SACT database. All reimbursed treatment options including the COVID interim treatment guidelines options were included. Patients who received SACT as part of a clinical trial were also included. Patients who remained on the respective lines of treatment were censored. Results: Data for 515 patients (372 male: 143 female) who received first-line SACT for mRCC were included in the analyses. IMDC prognostic groups were 103 favourable, 236 intermediate, 127 poor (49 not available). On progression 69% of patients were able to receive second-line therapy and 34% were able to receive third-line therapy. Of the 515 first-line therapies, 24% of patients received frontline ipilimumab and nivolumab, 10% received TKI and IO combination and 63% received single agent VEGF TKI. Second-line nivolumab or cabozantinib (43% and 40% respectively) were the most commonly prescribed options. Third-line cabozantinib 61% and nivolumab 16% remain the most used options. Across all lines of therapy progressive disease was the primary reason for discontinuation. 5% switched treatment due to toxicity. Conclusions: These results suggest that, with more treatment options available, including combination/ immunotherapy therapies, more patients are able to receive second and third-line therapies. Despite this, nearly one third of patients only receive one line of treatment which highlights the need to deliver the most efficacious treatments first to optimise patient outcomes. Moreover, single agent TKI was the most commonly used first-line SACT despite advances in the management pathway. Data analysing the impact of COVID on treatment selection will be presented.[Table: see text]

CLL-045: Long-Term Follow-up, Up to 7 Years, in the RESONATE-2 Study of First-Line Ibrutinib Treatment for Chronic Lymphocytic Leukemia (CLL)

Objective: Report RESONATE-2 phase 3 study extended long-term follow-up of first-line ibrutinib vs chlorambucil in older patients with CLL/SLL. Methods: Patients (≥65 years [y]) with previously untreated CLL/SLL (without del[17p]) were randomly assigned 1:1 to once-daily ibrutinib 420 mg, until disease progression (PD) or unacceptable toxicity (n=136); or chlorambucil 0.5–0.8 mg/kg, up to 12 cycles (n=133). Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety. Long-term responses were investigator-assessed per 2008 iwCLL criteria. Results: With up to 7y of follow-up (median, 74.9 months; range, 0.1–86.8), significant PFS benefit was sustained for patients treated with ibrutinib vs chlorambucil (HR 0.160 [95% CI: 0.111–0.230]). At 6.5y, PFS was 61% vs 9% for ibrutinib vs chlorambucil. PFS benefit was observed consistently, including ibrutinib-treated patients with high-risk genomic features of unmutated IGHV (HR 0.109 [95% CI: 0.063–0.189]) or del(11q) (HR 0.033 [95% CI: 0.010–0.107]). With ibrutinib, 6.5y OS was 78%; ORR was 92%, and complete response (CR/CRi) rate increased to 34%. Ongoing rates of grade ≥3 AEs of interest remained low for hypertension (5–6y interval: 5%, n=4; 6–7y: 4%, n=3) and atrial fibrillation (5–6y: 1%, n=1; 6–7y: 1%, n=1); no grade ≥3 major hemorrhage in 5–7y. One patient (1%) had dose reduction due to grade ≥3 AEs during years 5–6/6–7. Of 31 patients with dose reductions due to any-grade AEs over full follow-up, 22 (71%) had AE resolution/improvement. Primary reason for discontinuation was PD (5–6y: 5%, n=4; 6–7y: 6%, n=4). Any-grade AEs leading to discontinuations were 3% (n=2) in 5–6y and none in 6–7y. With up to 7y of follow-up, 47% of patients remain on single-agent ibrutinib. Conclusions: Long-term RESONATE-2 data demonstrate sustained PFS and OS benefit with first-line ibrutinib treatment for CLL, including for patients with high-risk genomic features. Responses continued to deepen over time. Rates of grade ≥3 AEs of interest continued to be low with rare further discontinuations and dose reductions due to AEs; most AEs leading to dose reduction resolved/improved. Ibrutinib remains well tolerated with no new safety signals. Funding: Pharmacyclics LLC, an AbbVie Company.

K.Vita: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy.

This prospective open-label feasibility study aimed to evaluate acceptability, tolerability and compliance with dietary intervention with K.Vita, a medical food containing a unique ratio of decanoic acid to octanoic acid, in individuals with drug-resistant epilepsy. Adults and children aged 3–18 years with drug-resistant epilepsy took K.Vita daily whilst limiting high-refined sugar food and beverages. K.Vita was introduced incrementally with the aim of achieving ≤35% energy requirements for children or 240 ml for adults. Primary outcome measures were assessed by study completion, participant diary, acceptability questionnaire and K.Vita intake. Reduction in seizures or paroxysmal events was a secondary outcome. 23/35 (66%) children and 18/26 (69%) adults completed the study; completion rates were higher when K.Vita was introduced more gradually. Gastrointestinal disturbances were the primary reason for discontinuation, but symptoms were similar to those reported from ketogenic diets and incidence decreased over time. At least three-quarters of participants/caregivers reported favourably on sensory attributes of K.Vita, such as taste, texture and appearance, and ease of use. Adults achieved a median intake of 240 ml K.Vita, and children 120 ml (19% daily energy). Three children and one adult had ß-hydroxybutyrate >1 mmol/l. There was 50% (95% CI 39–61%) reduction in mean frequency of seizures/events. Reduction in seizures or paroxysmal events correlated significantly with blood concentrations of medium chain fatty acids (C10 and C8) but not ß-hydroxybutyrate. K.Vita was well accepted and tolerated. Side effects were mild and resolved with dietetic support. Individuals who completed the study complied with K.Vita and additional dietary modifications. Dietary intervention had a beneficial effect on frequency of seizures or paroxysmal events, despite absent or very low levels of ketosis. We suggest that K.Vita may be valuable to those with drug-resistant epilepsy, particularly those who cannot tolerate or do not have access to ketogenic diets, and may allow for more liberal dietary intake compared to ketogenic diets, with mechanisms of action perhaps unrelated to ketosis. Further studies of effectiveness of K.Vita are warranted.

Ruxolitinib discontinuation in polycythemia vera: Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database

Ruxolitinib is approved for the treatment of patients with polycythemia vera (PV) who are intolerant or resistant to hydroxyurea. While ruxolitinib discontinuation in myelofibrosis is associated with dismal outcomes, the analogous experience in PV has not been reported. Using a large, multi-institutional database of PV patients, we identified 93 patients with PV who were treated with ruxolitinib, of whom 22 discontinued therapy. Adverse events were the primary reason for discontinuation. After a median follow-up of 18.2 months following ruxolitinib discontinuation, no patients experienced a thrombotic event. One patient died 20.8 months after discontinuation. As compared with the 71 patients who were still receiving treatment with ruxolitinib at last follow up, patients who discontinued ruxolitinib were older at time of treatment initiation (67.5 versus 64.8 years, p = 0.0058), but had similar patient and disease characteristics. After discontinuation, only 4 patients (18 %) received subsequent cytoreductive therapy, including hydroxyurea in one patient and pegylated interferon α-2a in three patients. In stark contrast to the experience in myelofibrosis, discontinuation of ruxolitinib in PV was associated with generally favorable outcomes. However, there is a lack of available salvage therapies, highlighting the need for further therapeutic development in PV.

Oral ixazomib-dexamethasone versus oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma (MM) patients: A global, multicenter, randomized, open-label, phase 2 trial.

8020 Background: MM patients (pts) often receive several lines of therapy with multiple drug combinations and, as lenalidomide (R)-containing regimens are commonly used as first-line therapy, R-free options for subsequent lines are necessary. Additionally, as pts age and become less tolerant to treatment, more convenient regimens, such as all-oral options, with less toxicity are needed. Dexamethasone (dex)-based doublets are effective and tolerable in this setting. Methods: Proteasome inhibitor (PI)-exposed and/or intolerant and R-refractory pts who had ≥2 prior therapies (N = 122) were randomized 3:2 to receive: ixazomib (ixa) 4 mg (5.5 mg from cycle 2 if tolerated) on day (d) 1, 8, 15, and dex 20 mg (≥75 years [yrs], 10 mg) on d 1, 2, 8, 9, 15, 16, 22, 23; or pomalidomide (pom) 4 mg on d 1–21, and dex 40 mg (≥75 yrs, 20 mg) on d 1, 8, 15, 22, in 28-d cycles until progressive disease (PD) or unacceptable toxicity. Pts were stratified by age ( < 65 vs ≥65 yrs), International Staging System (ISS) disease stage at study entry (I/II vs III), and prior lines of therapy (2 vs ≥3). The study was powered to test the primary endpoint of progression-free survival (PFS). Results: In the ixa-dex (n = 73) vs pom-dex (n = 49) arms, median age was 72 vs 68 yrs (36% vs 18% ≥75 yrs), 25% vs 22% of pts had ISS stage III MM, and 52% vs 53% had received ≥3 prior therapies (per stratification). At data cutoff (5/31/2020), 19% vs 20% of pts were ongoing on treatment with ixa-dex vs pom-dex; primary reasons for discontinuation were PD (47% vs 57%) and adverse events (AEs; 23% vs 12%). With median follow-up of 15.3 vs 17.3 months (mos), median PFS (mPFS) was 7.1 vs 4.8 mos with ixa-dex vs pom-dex (hazard ratio [HR] 0.847; 95% confidence interval [CI] 0.535–1.341; p = 0.477); the Table shows mPFS by prior lines, and secondary endpoints. Pts received a median of 6 cycles with both ixa-dex (range 1–25) and pom-dex (range 1–27); 64% of ixa-dex pts were able to escalate to a 5.5 mg dose of ixa. 69% vs 81% of ixa-dex vs pom-dex pts had grade (G) ≥3 AEs, 51% vs 53% had serious AEs, 39% vs 36% had an AE leading to drug discontinuation, 44% vs 32% had an AE leading to dose reduction, and 13% vs 13% died on study. Health-related quality of life (HRQoL; EORTC QLQ-C30/MY20, and EQ-5D-5L) was maintained, and similar between arms. Conclusions: Ixa-dex prolonged PFS vs pom-dex in these heavily pretreated, PI-exposed and/or intolerant, R-refractory pts, but the difference was not statistically significant. Ixa-dex was well tolerated, with lower G≥3 AE rates vs pom-dex, and comparable HRQoL. Clinical trial information: NCT03170882.

First long-term results on efficacy and safety of long-acting pasireotide in combination with everolimus in patients with advanced carcinoids (NET) of the lung/thymus: Phase II LUNA trial.

8574 Background: Everolimus (EVE) improves progression-free survival (PFS) in patients (pts) with progressive non-functioning thoracic and digestive advanced neuroendocrine tumors (NET). The LUNA trial aimed to assess the efficacy and safety of long-acting pasireotide (PAS) and EVE alone or in combination in pts with progressive bronchial or thymic carcinoids. Core phase results for primary endpoint (PFS) and secondary endpoints at 9 and 12 months (mo) were previously published. Cumulative data results at the end of the extension phase are presented here. Methods: LUNA was a prospective, multicenter, randomized, open-label, 3-arm, phase II trial. Adult pts with carcinoids of lung/thymus were randomized (1:1:1) to receive either PAS (60 mg/mo i.m.) or EVE (10 mg/day orally) or PAS + EVE. The key secondary endpoints assessed in this extension phase, including all the patients who were still not progressing at 12 months, were PFS, duration of biochemical response (DBR), and biochemical PFS (BPFS). Results: Of the total 124 pts included in the core phase, 41 pts with a median age of 61 years entered the extension phase including PAS (12), EVE (14) and PAS + EVE (15). Lung was the primary site of cancer in 95.1% and 82.9% had non-functioning tumors. Surgery/local or regional therapy was the preferred prior treatment in 63.4% pts. Disease progression was the primary reason for discontinuation among 3 arms with 65.9% in overall extension phase; no pts in PAS arm discontinued due to adverse events (AEs). Mean relative dose intensity (RDI) was higher for PAS (95.6% alone and 90.4% in combination) when compared to EVE (76.6% alone and 72.4% in combination); 38.1% pts in the EVE arm and 43.9% pts in the combination arm with EVE had RDI <70%. PAS +EVE combination showed clinical benefit in terms of PFS and BPFS compared to PAS and EVE alone as shown in Table. At least one dose reduction of PAS or EVE was reported in >50% pts. Most common AEs of any grade regardless of the study drug in PAS +EVE arm were hyperglycemia (87.8%), diarrhea (80.5%), and weight loss (58.5%), while stomatitis was reported in 34.1%. Twelve deaths were reported during the study and up to 56 days from last study treatment dose. Duration of exposure and efficacy. Conclusions: Mature median PFS and BPFS data suggest a benefit of PAS+EVE combination. The safety and tolerability profile of PAS and EVE alone or in combination were consistent with prior experience of these treatments in the oncology setting, with no new safety signals being reported during the study. Post-hoc prognostic studies are ongoing. Clinical trial information: NCT01563354. [Table: see text]