Impact of a Best Practices Program in Patients with Relapsed/Refractory Multiple Myeloma Receiving Selinexor.

Best practice (BP) in cancer care consists of a multifaceted approach comprising individualized treatment plans, evidence-based medicine, the optimal use of supportive care and patient education. We investigated the impact of a BP program in patients with relapsed/refractory multiple myeloma (RRMM) receiving selinexor. Features of the BP program that were specific to selinexor were initiating selinexor at doses ≤80 mg once weekly and the upfront use of standardized antiemetics. Study endpoints included time to treatment failure (TTF), duration of therapy, dose limiting toxicities and overall survival. Comparative analysis on TTF and duration of therapy was conducted using a log-rank test and multivariate Cox proportional hazard regression. Over the ensuing 12-month post-BP period, 41 patients received selinexor-based therapy compared to 68 patients who received selinexor-based therapy pre-BP implementation. Patients treated in the post-BP period had reductions in TTF (hazard ratio [HR] = 0.50; 95% CI: 0.27 to 0.92). Patients in the pre-BP period were four times more likely to stop therapy than those in the post-period (odds ratio [OR] = 4.0, 95% CI: 1.75 to 9.3). The findings suggest a BP program tailored to selinexor could increase the time to treatment failure, increase treatment duration and lower the incidence of drug limiting toxicities.

Compromised Outcomes in Stage IV Non-Small-Cell Lung Cancer With Actionable Mutations Initially Treated Without Tyrosine Kinase Inhibitors: A Retrospective Analysis of Real-World Data.

PURPOSE: Identification and targeting of actionable oncogenic drivers (AODs) in advanced non-small-cell lung cancer (NSCLC) has dramatically improved outcomes. However, genomic testing uptake is variable and hampered by factors including slow turnaround time, frequently resulting in initial non-tyrosine kinase inhibitor (TKI) treatment. We investigate how this behavior affects outcomes. METHODS: This retrospective analysis of real-world, deidentified data from the Integra Connect Database included adults with stage IV NSCLC newly diagnosed from January 1, 2018, to December 31, 2020, with mutations of EGFR, ALK, ROS1, BRAF, MET, RET, ERBB2, or NTRK. Outcomes were reported as time to next treatment or death (TTNT) and overall survival (OS). RESULTS: Five hundred ten patients harboring AODs were identified and grouped as follows: group A (n = 379) were treated after the AOD was reported and served as the comparator. One hundred thirty-one patients treated before their AOD report were divided into group B (n = 47) who were initially started on chemotherapy and/or checkpoint inhibitor but switched to appropriate TKI within 35 days and group C (n = 84) who were also started empirically on non-TKI and did not switch within 35 days. Survival (OS) was significantly superior in group A compared with group C; TTNT was significantly superior in group A compared with groups B and C. CONCLUSION: For patients harboring AODs in advanced NSCLC, initial treatment before receipt of genomic test results yields significantly inferior outcomes and should be avoided. Molecular profiling panels with rapid turnaround times are essential to optimize patient outcomes and should be standard of care.

Safety and efficacy of first-line nivolumab plus ipilimumab alternating with nivolumab monotherapy in patients with advanced renal cell carcinoma: the non-randomised, open-label, phase IIIb/IV CheckMate 920 trial.

OBJECTIVES: The non-randomised, open-label, phase IIIb/IV multicohort CheckMate 920 trial explored the safety and efficacy with a less frequent, but continual nivolumab plus ipilimumab (NIVO+IPI) dosing regimen (cohort 1) to determine whether this modification could potentially retain efficacy benefits while improving on the manageable safety profile previously observed with this combination in patients with advanced renal cell carcinoma (aRCC). SETTING: Patients were enrolled from 48 largely community-based sites in the USA. PARTICIPANTS: 106 patients with previously untreated, predominantly clear cell aRCC received treatment. INTERVENTIONS: Patients received NIVO 6 mg/kg plus IPI 1 mg/kg on day 1 of the first week of each 8-week cycle; the combination alternated with NIVO 480 mg monotherapy on day 1 of the fifth week of each 8-week cycle. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or study end. The maximum treatment duration was 2 years. The primary endpoint was the incidence of high-grade (grade 3/4 and grade 5) immune-mediated adverse events (IMAEs) within 100 days of the last dose. Select secondary endpoints included time to onset and resolution of high-grade IMAEs, progression-free survival (PFS) and objective response rate (ORR). The incidence of treatment-related adverse events and the overall survival (OS) were the exploratory endpoints. RESULTS: The most common grade 3/4 IMAEs were diarrhoea/colitis (7.5%) and rash (6.6%) and no grade 5 IMAEs occurred, with a minimum follow-up of 28.5 months. The median PFS was 4.8 (95% CI 3.0 to 8.3) months, the ORR in evaluable patients (n=96) was 34.4% (95% CI 25.0 to 44.8), and the median OS was not reached (95% CI 24.8 months to not estimable). CONCLUSIONS: While no new safety signals were reported with less frequent, but continual NIVO+IPI dosing in CheckMate 920, the modified regimen was not associated with clinical benefits relative to the approved NIVO+IPI dose. These results support the continued use of the currently approved NIVO+IPI combination dosing schedule for patients with aRCC. TRIAL REGISTRATION NUMBER: NCT02982954.

Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase 3b/4 CheckMate 920 trial.

BACKGROUND: CheckMate 920 (NCT02982954) is a multicohort, phase 3b/4 clinical trial of nivolumab plus ipilimumab treatment in predominantly US community-based patients with previously untreated advanced renal cell carcinoma (RCC) and clinical features mostly excluded from phase 3 trials. We report safety and efficacy results from the advanced non-clear cell RCC (nccRCC) cohort of CheckMate 920. METHODS: Patients with previously untreated advanced/metastatic nccRCC, Karnofsky performance status ≥70%, and any International Metastatic Renal Cell Carcinoma Database Consortium risk received up to four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks followed by nivolumab 480 mg every 4 weeks for ≤2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥3 immune-mediated adverse events (AEs) within 100 days of last dose of study drug. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS; both investigator-assessed), time to response (TTR), and duration of response (DOR), all using RECIST V.1.1. Overall survival (OS) was exploratory. RESULTS: Fifty-two patients with nccRCC (unclassified histology, 42.3%; papillary, 34.6%; chromophobe, 13.5%; translocation-associated, 3.8%; collecting duct, 3.8%; renal medullary, 1.9%) received treatment. With 24.1 months minimum study follow-up, median duration of therapy (range) was 3.5 (0.0-25.8) months for nivolumab and 2.1 (0.0-3.9) months for ipilimumab. Median (range) number of doses received was 4.5 (1-28) for nivolumab and 4.0 (1-4) for ipilimumab. Grade 3-4 immune-mediated AEs were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). No grade 5 immune-mediated AEs occurred. ORR (n=46) was 19.6% (95% CI 9.4 to 33.9). Two patients achieved complete response (papillary, n=1; unclassified, n=1), seven achieved partial response (papillary, n=4; unclassified, n=3), and 17 had stable disease. Median TTR was 2.8 (range 2.1-14.8) months. Median DOR was not reached (range 0.0+-27.8+); eight of nine responders remain without reported progression. Median PFS (n=52) was 3.7 (95% CI 2.7 to 4.6) months. Median OS (n=52) was 21.2 (95% CI 16.6 to not estimable) months. CONCLUSIONS: Nivolumab plus ipilimumab for previously untreated advanced nccRCC showed no new safety signals and encouraging antitumor activity. TRIAL REGISTRATION NUMBER: NCT02982954.

Daratumumab utilization and cost analysis among patients with multiple myeloma in a US community oncology setting.

Background: The introduction of daratumumab into the treatment of multiple myeloma has improved outcomes in patients; however, community oncologists often dose more frequently than the US FDA-approved label. Materials and methods: Integra analyzed its database to elucidate daratumumab treatment patterns and the impact of increased utilization on the cost of care for multiple myeloma. Results: Following week 24, 671 (65%) of 1037 patients remained on daratumumab-containing regimens, with 330 patients continuing more frequent treatments than the expected once-every-4-weeks dosing described in the standard dosing schedule. Patients received an average of 14% more daratumumab doses than the FDA-approved label indicates, increasing the 1-year daratumumab costs by an estimated US$31,353. Conclusion: Daratumumab is utilized more frequently than the FDA-recommended dosing, leading to higher multiple myeloma treatment costs.

Lay abstract Since its first approval in 2015, daratumumab has become the backbone of many multiple myeloma treatment regimens. While its approval has improved outcomes in many patients who undergo treatment, it is expensive and has largely contributed to the increasing costs of care in multiple myeloma. In its most common treatment schedule, patients should transition from weekly and biweekly dosing to treatment once every 4 weeks. However, many providers maintain their patients on a more frequent dosing schedule, which increases Medicare 1-year costs by an estimated US$31,353 and may have unforeseen impacts on adverse events and patient outcomes.

Safety and efficacy of nivolumab plus ipilimumab in patients with advanced renal cell carcinoma with brain metastases: CheckMate 920.

BACKGROUND: Nivolumab plus ipilimumab (NIVO + IPI) has demonstrated long-term efficacy and safety in patients with previously untreated, advanced renal cell carcinoma (aRCC). Although most phase 3 clinical trials exclude patients with brain metastases, the ongoing, multicohort phase 3b/4 CheckMate 920 trial (ClincalTrials.gov identifier NCT02982954) evaluated the safety and efficacy of NIVO + IPI in a cohort that included patients with aRCC and brain metastases, as reported here. METHODS: Patients with previously untreated aRCC and asymptomatic brain metastases received NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks × 4 followed by NIVO 480 mg every 4 weeks. The primary end point was the incidence of grade ≥3 immune-mediated adverse events (imAEs) within 100 days of the last dose of study drug. Key secondary end points were progression-free survival and the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1 (both determined by the investigator). Exploratory end points included overall survival, among others. RESULTS: After a minimum follow-up of 24.5 months (N = 28), no grade 5 imAEs occurred. The most common grade 3 and 4 imAEs were diarrhea/colitis (n = 2; 7%) and hypophysitis, rash, hepatitis, and diabetes mellitus (n = 1 each; 4%). The objective response rate was 32% (95% CI, 14.9%-53.5%) with a median duration of response of 24.0 months; 4 of 8 responders remained without reported progression. Seven patients (25%) had intracranial progression. The median progression-free survival was 9.0 months (95% CI, 2.9-12.0 months), and the median overall survival was not reached (95% CI, 14.1 months to not estimable). CONCLUSIONS: In patients who had previously untreated aRCC and brain metastases-a population with a high unmet medical need that often is underrepresented in clinical trials-the approved regimen of NIVO + IPI followed by NIVO showed encouraging antitumor activity and no new safety signals.

Impact of Late Dosing on Testosterone Suppression with 2 Different Leuprolide Acetate Formulations: In Situ Gel and Microsphere. An Analysis of United States Clinical Data.

PURPOSE: Nonadherence to dosing schedules for androgen deprivation therapy increases the risk of testosterone escape for patients with prostate cancer. Two approved formulations of leuprolide acetate, the most commonly prescribed androgen deprivation therapy in the United States, use different extended release delivery technologies: an in situ gel and microspheres. We evaluated the prevalence and impact of late dosing on testosterone suppression for gel and microsphere formulations of leuprolide acetate. MATERIALS AND METHODS: We retrospectively analyzed records of patients with prostate cancer treated with gel or microsphere delivery of leuprolide acetate. Analyses used 2 definitions of "month," "28-day" (late dosing after day 28, 84, 112 or 168) and "extended" (late dosing after day 32, 97, 128 and 194). Frequencies of late dosing and associated testosterone values were calculated. RESULTS: A total of 2,038 patients received gel and 8,360 received microsphere formulations of leuprolide acetate. More than 80% and 27% of injections were late for 28-day and extended month, respectively. For 28-day month late injections 10% (gel delivery) and 14% (microsphere delivery) of testosterone values were above 50 ng/dl, and 25% (gel) vs 33% (microsphere) were above 20 ng/dl. For extended month 18% (gel) vs 25% (microsphere) were above 50 ng/dl, and 34% (gel) vs 44% (microsphere) were above 20 ng/dl. Microsphere leuprolide acetate was 1.5 times more likely to have testosterone above 50/20 ng/dl vs gel. Least square mean testosterone was 34 ng/dl (gel) vs 46 ng/dl (microsphere) for 28-day month, and 48 ng/dl (gel) vs 76 ng/dl (microsphere) for extended month. CONCLUSIONS: Leuprolide acetate therapies were frequently administered late. Gel formulation demonstrated higher rates of testosterone 50 ng/dl or less and 20 ng/dl or less than microsphere formulation. Optimal testosterone suppression can impact prostate cancer progression and patient survival, and differences in extended release technology for androgen deprivation therapy appear relevant.

Impact of the COVID-19 pandemic on specialty community practices: an oncology perspective.

OBJECTIVES: Typically, a community-based specialty practice is prepared for a limited public health crisis that is driven by a natural disaster or a localized environment event. This article describes the unexpected impact that the coronavirus disease 2019 (COVID-19) pandemic has had on community-based specialty practices across the United States, especially oncology practices. STUDY DESIGN AND METHODS: We conducted an electronic national survey of community-based specialty practice administrators to determine the impact of COVID-19 on their practices and their ability to manage through a global pandemic. The 22-question survey focused on an initial observation period of March 15, 2020, to May 15, 2020, compared with a second period of May 16, 2020, to August 15, 2020. RESULTS: Oncology practices accounted for 46% of the 155 specialty practices that participated in the survey. Overall, 57% of respondents saw at least a 30% decline in total patient volume and/or financial impact during the initial observation period, compared with a 38% decline for the oncology practices. More than 70% of all practices experienced improvement after May 15, 2020, with at least 60% improving regardless of specialty. The initial decline was primarily driven by declines in new patient volume and procedures. Approximately 62% of practices anticipate a moderate-to-significant impact on patient outcomes over the next 12 months. The impact expected was slightly higher in retina and ophthalmology practices than oncology. CONCLUSIONS: Although unexpectedly impacted in delivering care for their patients, specialty practices generally and oncology practices especially have been resilient by leveraging federal funds and adopting operational enhancements.

The Impact of Late Luteinizing Hormone-Releasing Hormone Agonist Dosing on Testosterone Suppression in Patients with Prostate Cancer: An Analysis of United States Clinical Data.

PURPOSE: We evaluated the timeliness of androgen deprivation therapy dosing, the impact of dosing nonadherence on testosterone, and the frequency of testosterone and prostate specific antigen testing in patients with prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed the records of 22,860 patients with prostate cancer treated with luteinizing hormone-releasing hormone agonists. Analyses were done using 2 definitions of month, including a 28-day month (late dosing after day 28, 84, 112 or 168) and an extended month (late after day 32, 97, 128 or 194) for 1, 3, 4 and 6-month formulations, respectively. The prevalence of late dosing, associated testosterone values, and the frequency of testosterone and prostate specific antigen testing were assessed. Statistical significance was assessed with the unpaired t-test. RESULTS: Of the injections 84% and 27% were late for the 28-day and extended month analyses, respectively. For the 28-day month 60% and 29% of injections were late by more than 1 and more than 2 weeks, respectively. Of testosterone values 4% were greater than 50 ng/dl for early/on time injections using both definitions, and 15% and 27% were greater than 50 ng/dl when late, and for the 28-day month and the extended month, respectively. For early/on time vs late injections 22% vs 31% of testosterone values were greater than 20 ng/dl for the 28-day month and 21% vs 43% for the extended month. Mean testosterone was higher when late (49 ng/dl for 28-day month, 79 ng/dl for extended month) vs early/on time (both 21 ng/dl). Of the injections prostate specific antigen measurements were performed in 83% and testosterone assessment was done in only 13%. CONCLUSIONS: Luteinizing hormone-releasing hormone agonists were frequently (84%) administered later than the schedules used in pivotal trials. Nearly half of the late testosterone values for the extended month were greater than 20 ng/dl and mean testosterone was almost double the castration level. Elevated testosterone remained unidentified with infrequent testing.

Recent study on site of care has severe limitations.

The outpatient community oncology setting is consistently less costly for cancer treatment as opposed to the outpatient hospital setting.

Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study.

PURPOSE: A novel transdermal formulation of granisetron (the granisetron transdermal delivery system (GTDS)) has been developed to deliver granisetron continuously over 7 days. This double-blind, phase III, non-inferiority study compared the efficacy and tolerability of the GTDS to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV). PATIENTS AND METHODS: Six hundred forty-one patients were randomized to oral (2 mg/day, 3-5 days) or transdermal granisetron (one GTDS patch, 7 days), before receiving multi-day chemotherapy. The primary endpoint was complete control of CINV (no vomiting/retching, no more than mild nausea, no rescue medication) from chemotherapy initiation until 24 h after final administration. The prespecified non-inferiority margin was 15%. RESULTS: Five hundred eighty-two patients were included in the per protocol analysis. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation. CONCLUSIONS: The GTDS provides effective, well-tolerated control of CINV associated with moderately or highly emetogenic multi-day chemotherapy. It offers a convenient alternative route for delivering granisetron for up to 7 days that is as effective as oral granisetron.

Randomized, open-label comparison of epoetin alfa extended dosing (80 000 U Q2W) vs weekly dosing (40 000 U QW) in patients with chemotherapy-induced anemia.

OBJECTIVE: This randomized, open-label, multicenter study compared the efficacy and safety of epoetin alfa (EPO) 80 000 U every 2 weeks (Q2W) to the FDA-approved regimen of 40 000 U weekly (QW) in patients with chemotherapy-induced anemia. RESEARCH DESIGN AND METHODS: A total of 310 patients with nonmyeloid malignancy and baseline hemoglobin (Hb)

Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders.

PURPOSE: To determine the feasibility and efficacy of pharmacokinetic (PK) -based maintenance dosing of rituximab and possibly design a more rational maintenance schedule. PATIENTS AND METHODS: Patients with CD20-positive lymphoproliferative disorders were treated with four weekly infusions of rituximab 375 mg/m(2). All patients without progressive disease were then monitored for 1 year and received a single infusion of 375 mg/m(2) when the level decreased below 25 microg/mL. RESULTS: Twenty-nine of 31 patients were assessable with a variety of histologic subtypes. The overall response rate (ORR) for the entire group was 59% with 27% complete responses (CRs) and 32% partial responses. The median PFS for all patients was 19 months, with a median follow-up of 25 months. In 22 patients with low-grade non-Hodgkin's lymphoma (LGNHL), the ORR was 63% with 36% CR and median progression-free survival (PFS) has not been reached. Of 29 assessable patients, 22 were available for PK-based maintenance. The median time to repeat bolus was 5 months (range, 1 to 9 months) for the first, 3.5 months (range, 2 to 5 months) for the second, and 3 months (range, 2 to 4 months) for the third infusion. Ninety-five percent of patients required three or fewer infusions to be maintained in the therapeutic range. CONCLUSION: Individualized PK dosing for rituximab produced efficacy comparable to other published maintenance strategies. PK data from this trial suggest that a rational maintenance strategy in patients with LGNHL would be a single dose of 375 mg/m(2) of rituximab every 3 to 4 months.