scholarly journals Interim Results of the Observational Study Caro: Twice Weekly Carfilzomib Is a Convenient Treatment Option for Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5662-5662
Author(s):  
Wolfgang Knauf ◽  
Andreas Ammon ◽  
Jens Uhlig ◽  
Marie Merling ◽  
Hans-Juergen Hurtz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Treatment Option ◽  
Real World ◽  
Interim Analysis ◽  
Dose Intensity ◽  
Recommended Dose ◽  
Treatment Recommendation ◽  
Dosing Regimen ◽  
Dosing Schedule ◽  
Prior Therapy

Abstract Introduction: Poor adherence and persistence to anticancer treatment are serious issues in the management of cancer patients since nonadherence has been shown to lead to higher treatment failure rates, worse outcome and higher total costs of care. The combination of the proteasome inhibitor carfilzomib (Kyprolis®) with lenalidomide (Revlimid®) and dexamethasone (CAR/LEN/DEX) or with dexamethasone alone (CAR/DEX) is approved for the treatment of patients with multiple myeloma who have received at least one prior therapy. According to the current approved schedule, carfilzomib has to be given twice weekly in both regimens. Real-world data on the implementation of this treatment recommendation are still limited. Methods: The prospective, multicenter, non-interventional, observational CARO study was designed to collect data on 300 patients with multiple myeloma (CAR/LEN/DEX: 200, CAR/DEX: 100) from 90 sites across Germany. Primary objective is patients' adherence and persistence to carfilzomib therapy as prescribed by the treating physician according to current Summary of Product Characteristics (SmPC). Secondary objectives are patients' adherence and persistence to lenalidomide and dexamethasone as well as the real-world implementation of the recommended CAR/LEN/DEX or CAR/DEX dosing regimen in clinical routine (i.e., the comparison of actually administered medication versus recommended medication according to current SmPC). Exploratory objectives are effectiveness, safety and health-related quality of life. The first interim analysis of the CARO study was scheduled to assess the primary and secondary endpoints 12 months after the recruitment of the first patient. Results: Between October 2016 and October 2017, 102 patients had been enrolled, thereof 68 patients into the CAR/LEN/DEX cohort and 32 patients into the CAR/DEX cohort at the time of the pre-specified interim analysis (database cut: 25 October 2017). Here, the focus is on the adherence of the twice weekly carfilzomib schedule in evaluable patients who received CAR/LEN/DEX (N=64) and on the implementation of the SmPC in terms of timing, dosing and frequency. Median age of patients was 72.3 years (range 43.4-84.3), 45.3% were female and 70.3% of the patients had a good performance status (PS) with a Karnofsky PS score of 80 to 100. The relative mean dose intensity of carfilzomib was 88.1%. 1368 of the scheduled 1591 carfilzomib administrations (86.0%) were given in time. 7.9% (n=125) of administrations were omitted, 5.0% (n=80) of administrations were delayed and 1.1% (n=18) of doses were administered earlier. Carfilzomib was omitted at least once in 43.8% of patients (n=28). 62.5% (n=40) and 18.8% (n=12) of patients, respectively, had a delayed or earlier carfilzomib administration documented at least once during their course of treatment. Reasons for deviations from the recommended carfilzomib dosing schedule concerning timing are depicted in Table 1. 1328 of 1466 carfilzomib administrations (90.6%) were given at the recommended dose. 6.2% (n=91) of doses were reduced. The main reason for dose reduction was the occurrence of adverse events (4.0%, n=58). Other reasons were: nonadherence (1.2%, n=18), organizational reasons (0.1%, n=2) and others (0.9%, n=13). 23.4% (n=15) of patients received at least one reduced carfilzomib dose during their course of treatment. The mean adherence to the carfilzomib dosing regimen (i.e., the percentage of doses administered as scheduled by the treating physician and not modified for adherence reasons) was 94.8%. Conclusion: According to our interim results, 86% of carfilzomib administrations were given in time and more than 90% of administrations were given at the recommended dose. Deviations from the recommended carfilzomib regimen were mainly due to safety issues or organizational reasons, but not due to nonadherence. Carfilzomib treatment adherence was almost 95%. Though, despite the required twice weekly dosing schedule, the carfilzomib regimen seems to be a convenient treatment option for multiple myeloma patients. Results have to be confirmed at final analysis. Disclosures Knauf: Celgene: Consultancy, Honoraria; Roche: Consultancy; Amgen: Consultancy, Honoraria; Mundipharma: Consultancy; Gilead Sciences: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Marschner:Amgen: Consultancy, Honoraria; IOMEDICO: Employment, Equity Ownership; Sandoz: Honoraria.

scholarly journals An Ongoing, Observational Cohort Study in Multiple Myeloma (PREAMBLE): Preliminary Efficacy Analyses in Patients with 1 Line of Prior Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2403-2403
Author(s):  
Brian Durie ◽  
David J Kuter ◽  
Catherine Davis ◽  
Teresa Zyczynski ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Treatment Outcomes ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Hematologic Malignancy ◽  
Research Assessment ◽  
Advisory Committees ◽  
Prior Therapy

Abstract Introduction: Multiple myeloma (MM) is an incurable hematologic malignancy associated with high disease burden and relapse rates. In recent years, several treatment options for MM have become available that have improved patient outcomes. However, robust data on real-world treatment outcomes associated with these MM treatments are sparse. PREAMBLE (Prospective REsearch Assessment in Multiple myeloma: an oBservationaL Evaluation; NCT01838512) is an ongoing multinational observational study that aims to increase understanding of real-world clinical effectiveness of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and combination therapy for relapsed/refractory MM (RRMM). Here, we present preliminary efficacy analyses on data from patients with 1 line of prior MM therapy both with and without prior transplantation experience. Methods: Eligible patients had a confirmed diagnosis of RRMM with 1 prior treatment and started treatment with an IMiD, PI, or IMiD+PI 90 days prior/30 days following study enrollment. Patient data were collected at each healthcare provider visit for a follow-up period of 3 years. Vital status was recorded every 6 months for all patients. Response rates (defined as minimal response or better) were assessed using cumulative incidence function, with progression as competing risk. Time in response, progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method. Results: Of 855 treated patients, 367 (43%) had 1 prior line of therapy (median age 70 years, 56% male). In this group, 71 (19%) had refractory disease, with even distribution among International Staging System stages I, II, and III. Index therapy was IMiD (n=193, 53%), PI (n=148, 40%), or IMiD+PI (n=26, 7%). At data cut-off (April 2016), median (Q1-Q3) follow-up was 16.7 (9-27) months, and 225 (61%) patients were still on study; the most common reasons for discontinuation were death or entering into a randomized clinical trial. Discontinuation was attributed to death for 92 (25%) patients; 69 (75%) of these deaths were due to disease progression. Approximately one-third of patients (128/367; 35%) had prior transplantation experience: 5% of patients had 2 prior transplantations, 99% of transplantations were autologous, and 83% were received after frontline (first) therapy. In patients without transplantation experience (n=238), the response rate (95% CI) was 46% (39-53) at 6 months, 58% (50-65) at 12 months, and 60% (53-67) at 18 months, versus 43% (34-53), 60% (50-70), and 60% (50-70), respectively, in those with prior transplantation. Median time in response was 14.6 months in patients without prior transplantation versus 20.3 months in those with prior transplantation. In patients with and without prior transplantation, time in response was longer in patients who had received an IMiD as index therapy (Table). Median PFS was 11.5 months in patients without transplantation and 14.1 months in those with transplantation; PFS rates (with/without prior transplantation) was: 6 months, 71%/67%; 12 months, 56%/49%; 18 months, 41%/32%. OS rate at 12 months was 81% in patients without prior transplantation and 82% in those with prior transplantation. In patients (≥6 months on study) who responded within 6 months, OS rate (IMiD/PI cohorts) was: 6 months, 100%/100%; 12 months, 93%/91%; 18 months, 85%/78%. In patients (≥6 months on study) who progressed within 6 months, OS rate (IMiD/PI cohorts) was: 6 months, 100%/100%; 12 months, 84%/69%; 18 months, 56%/64%. Conclusions: In patients with MM and 1 line of prior therapy either with or without prior transplantation experience, approximately 45% achieved a response, with approximately 40% of these patients maintaining their response at 18 months. Regardless of index therapy type or prior transplantation experience, loss of response was observed over time, highlighting the continuing unmet medical need in RRMM. Collectively, these data exemplify the importance of novel therapies that have potential to provide durable responses and improve treatment outcomes for patients with RRMM. Further analyses exploring any impact of prior transplantation and type of frontline therapy on treatment outcomes with subsequent lines of therapy are ongoing, and will be included in the final presentation. Study support: Bristol-Myers Squibb (BMS). Medical writing assistance was provided by K Rees, of Caudex, funded by BMS. Disclosures Durie: Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Kuter:Amgen: Consultancy; Eisai: Consultancy; Genzyme: Consultancy; GlaxoSmithKline: Consultancy; ONO: Consultancy; Pfizer: Consultancy; Shionogi: Consultancy; Shire: Consultancy; 3SBios: Consultancy; Bristol-Myers Squibb: Research Funding; Protalix: Research Funding; Rigel: Research Funding. Davis:Bristol-Myers Squibb: Employment. Zyczynski:Bristol-Myers Squibb: Employment. Goldschmidt:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Honoraria, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Vij:Amgen: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Consultancy; Takeda: Honoraria, Research Funding; Novartis: Honoraria; Karyopharm: Honoraria. Popov:Bristol-Myers Squibb: Consultancy. Cella:Abbvie, Inc.: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Bayer Pharmaceuticals, Inc.: Consultancy, Research Funding; Alexion, Inc., Astellas, Biogen Idec, Celgene, Clovis Oncology, Inc., Daiichi Sankyo, Eli Lilly, Evidera, Inc., Exelixis, Fiborgen, Genetech, Helsinn Therapeutics, Inc., Immunogen, Ipsen Pharma, Janssen, Lexicon Pharmaceuticals, Inc., Merck, Novartis, Onc: Consultancy, Research Funding; Facit.org: Other: President; Bristol-Meyers Squibb: Consultancy, Research Funding. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

A multicenter prospective randomized study testing non-inferiority of thalidomide 100 mg/day as compared with 400 mg/day in patients with refractory/relapsed multiple myeloma: Results of the final analysis of the IFM 01–02 study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7520-7520 ◽  
Author(s):  
I. Yakoub-Agha ◽  
C. Doyen ◽  
C. Hulin ◽  
G. Marit ◽  
L. Voillat ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Day Treatment ◽  
Randomized Study ◽  
Dose Intensity ◽  
Final Analysis ◽  
Patient Characteristics ◽  
University Hospital ◽  
Prospective Randomized Study ◽  
Prior Therapy ◽  
Vein Thrombosis

7520 Background: Thalidomide (THAL) is effective in pts with relapsed or refractory multiple myeloma (RRMM). A study by Yakoub-Agha et al of 83 patients (Hematol J, 2002) supported this effectiveness but showed a high incidence of THAL toxicity ≥ grade II, related to either THAL cumulative dose or dose-intensity. Themean daily dose of THAL in the first 90-day treatment period, however, did not influence response, overall survival (OS), or event-free survival. Given the dose-related toxicities and an unknown minimally effective THAL dose, the IFM conducted a prospective randomized study to compare the efficacy of THAL 100 mg/d with 400 mg/d in pts with RRMM after ≥2 lines of prior therapy. Methods: The study design was approved by the ethics committee at Lille University Hospital, and all pts gave written informed consent. Given the improved response seen with THAL plus dexamethasone (DEX), this combination was specified per protocol in both study arms for treatment failure (TF) defined as progression at any time or stable disease after 3 months of THAL treatment. THAL dose reduction for toxicity was permitted, but no increase over the initial dose was allowed. All pts received pamidronate routinely. The primary end point was 1-year OS. Secondary endpoints were response rate, EFS, and safety. Results: All results are based on intent-to-treat analyses. In all, 400 pts were enrolled (400 mg, n = 195; 100 mg, n = 205). The 2 groups were comparable in terms of patient characteristics, disease features including Ch13 deletion and prior therapy. Pts in the THAL 100 mg arm received DEX more frequently for TF than those in the 400 mg group, but this difference did not influence 1-year OS: 73 ± 3% vs 69 ± 3% in the 400 mg and 100 mg groups, respectively. The hypothesis of inferiority of 100 mg was rejected. Also, THAL 100 mg was better tolerated than 400 mg with less high-grade somnolence, constipation, and peripheral neuropathy (p < .001, p = .01 et p = .05, respectively). There was no difference regarding deep vein thrombosis. Conclusion: THAL 100 mg/d is comparable in terms of survival with 400 mg/d (with DEX as salvage therapy in case of TF in both arms) in pts with RRMM and better tolerated. [Table: see text]

An Ongoing Multinational Observational Study in Multiple Myeloma (PREAMBLE): Initial Assessment of Treatment Patterns in Patients with ≥6 Months Follow-up

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1297-1297
Author(s):  
Ravi Vij ◽  
Lieven Annemans ◽  
Catherine Davis ◽  
Trong K. Le ◽  
Blake Bartlett ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
North America ◽  
Disease Progression ◽  
Real World ◽  
Response Rate ◽  
Clinical Effectiveness ◽  
Treatment Patterns ◽  
Initial Assessment ◽  
Prior Therapy

Abstract INTRODUCTION Outcomes for patients with multiple myeloma (MM) have improved in the past decade with the use of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). There are, however, limited data on real-world effectiveness of these agents in the setting of relapsed/refractory MM (RRMM). PREAMBLE (Prospective REsearch Assessment in Multiple Myeloma: an OBservationaL Evaluation; NCT01838512) is an ongoing, prospective, multinational, observational cohort study to evaluate the real-world clinical effectiveness, healthcare resource utilization, and patient-reported outcomes associated with IMiD, PI, and IMiD+PI therapy in patients with RRMM. We present initial treatment patterns and clinical effectiveness in patients with ≥6 months of follow-up in the study. METHODS Patients aged ≥18 years with RRMM, ≥1 prior therapy and initiating treatment with an IMiD, PI, or IMiD+PI within 90 days prior to or 30 days after study enrollment (index therapy) were eligible. Treatment was administered according to standard clinical practice. Data were collected at baseline and every 3 (Year 1) and 6 (Years 2–3) months over 3 years or until study discontinuation. Assessment of clinical effectiveness included response rates and progression-free survival (PFS); response was based on defined criteria (e.g. European Group for Blood and Bone Marrow Transplant and International Myeloma Working Group criteria), or clinical judgment. RESULTS At the time of the data cut-off (8 May 2014), 274 patients were enrolled: 209 (76.3%) were still in the study, 65 (24%) had discontinued; 55 (85%) discontinuations were due to death. Results are reported for 189/274 (69%) patients (Europe n=105 [56%]; North America n=84 [44%]) with ≥6 months (median 11.1 months) follow-up; the majority (165/189; 87%) were alive at the data cut-off. Median time from diagnosis to start of index therapy was 41.0 months. Eighty-nine (49%) patients had 1 prior line of therapy (n=181); 58 patients (32%) had 2 lines of prior therapy (median 95 days between regimens). Most patients received prior regimens containing a PI (53%) or IMiD (46%); 19% received regimens containing both. Of patients receiving IMiD index therapy (n=87), 66% were from Europe and 35% were from North America; 52% and 48% of patients receiving PI index therapy (n=87) were from Europe and North America, respectively. Most patients with combination index therapy (IMiD+PI, n=15) were from North America (80%). Approximately half of patients (102/189; 54%) permanently discontinued or switched index treatment regimen, occurring after (median) 3.8 months, most often due to disease progression (20/102; 20%) or toxicity (20/102; 20%). Patients who switched (29/189; 15%) did so in (median) 21 days. The most common switch was bortezomib to lenalidomide (5/29; 17%); patients receiving lenalidomide most commonly switched to bortezomib (4/8; 50%). Around one fifth of patients (6/29; 21%) switched to a triplet regimen (IMiD+PI). Regional treatment patterns are planned for inclusion in the presentation. Median PFS was 9.0 months, 6-month PFS rate was 77%, and overall response rate was 39%. PFS and response rate by class of index regimen are provided in the table; subset analyses by line of therapy are planned for inclusion in the presentation. TableIMiD-based regimens (n=87)PI-based regimens (n=87)IMiD+PI-based regimens (n=15)PFS, median (95% CI) months9 (7, 12)11 (7, 13)7 (5, NE)6-month PFS rate, % (95% CI)79 (65, 88)76 (62, 85)69 (21, 91)Response rate, %, (95% CI)39 (29, 50)44 (33, 55)7 (0.2, 32) NE, not estimable due to insufficient follow-up time, limited number of patients, and limited number of events among these patients. CONCLUSIONS In this initial assessment of patients with ≥6 months of follow up in PREAMBLE, a greater proportion of patients from Europe received an IMiD as index therapy compared with those from North America. Treatment regimens were discontinued or switched for over half of patients, predominantly due to disease progression or toxicity. Additional follow-up is needed to better understand the implications of treatment patterns observed in real-world clinical practice, and specific reasons for disease progression and toxicity in patient subgroups and regions. Study funded by Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by Alyson Bexfield, Caudex Medical, funded by Bristol-Myers Squibb. Disclosures Vij: Sanofi: Honoraria; Novartis: Honoraria; Millennium: Honoraria; Janssen: Honoraria; Array: Honoraria; Onyx: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Annemans:Bristol-Myers Squibb: Consultancy. Davis:Bristol-Myers Squibb: Employment. Le:Bristol-Myers Squibb: Employment. Bartlett:Bristol-Myers Squibb: Employment; Bristol-Myers Squibb: Equity Ownership. Moreau:BMS, Celgene, Novartis, Millenium, Janssen: Honoraria; BMS, Celgene, Novartis, Millenium, Janssen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Daratumumab Dose Analysis Among Patients with Multiple Myeloma in a US Community Oncology Setting: A Retrospective Observational Study in Integra Connect Network

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Robert E Smith ◽  
Mei Xue ◽  
Stanley M. Marks ◽  
Jeffrey A. Scott ◽  
Simon Blanc ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Research Funding ◽  
Administrative Claims ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Dose Ratio ◽  
Dosing Schedule ◽  
Entire Cohort ◽  
Community Oncology

BACKGROUND Since the FDA's initial indication for the use of daratumumab in relapsed/refractory multiple myeloma (RRMM) in November 2015, usage has been expanded by subsequent approvals in newly diagnosed, transplant-ineligible MM patients, and more recently in newly diagnosed transplant-eligible patients. Real World Data (RWD) has been published demonstrating daratumumab's efficacy in RRMM settings[1]and its utility of split dosing for the initial dose[2]. However, no study has been published to examine the real-world dosing patterns of daratumumab compared to the FDA standard dosing schedule. While there are minimal variations in the approved dosing schedule of daratumumab, generally accepted dosing is weekly in week 1 through week 8, q 2 Wks in week 9 through week 24, and q 4 Wks after week 24, all at the standard 16 mg/kg dosage[3]. In its approved dosing schedule, adjustments are made in the frequency of administration, but not in the standard weight-based dosing. METHODS Utilizing the Integra Connect database which contains 17 community oncology network accounts and over 1,900 providers in US, we collected all MM patients treated with daratumumab between January 1, 2016 and March 31, 2020. We then excluded any patient whose first line of therapy (LOT) was ambiguous, in order to correctly identify the daratumumab-containing LOTs. We also excluded LOT 1 daratumumab transplant induction due to the wide variation in daratumumab dosing schedules in clinical trials in the transplant eligible patient[4]. LOTs were determined based on International Myeloma Working Group guidelines[5]. Data were collected on the date of each individual daratumumab administration, counting initial split dose, if utilized, as 1 dose. The duration of daratumumab and number of doses administered were calculated and corrected for any time on treatment breaks. The study was conducted per individual patient by LOT cohorts, and for the entire cohort of patients. We utilized the standard dose schedule for daratumumab noted above to establish the expected doses of daratumumab and calculated the compliance dose ratio (ratio of actual doses to expected doses per time on therapy) to evaluate how closely real-world treatment adhered to the standard dosing schedule. RESULTS 1037 MM patients were included with at least 6 doses of daratumumab administration and without stem cell transplant or uncertain LOT. Across all LOTs, the mean duration of daratumumab treatment was 5.6 months with a median duration of 9.8 months. After week twenty-four, 671 (65%) patients remained on daratumumab-containing regimens, with 330 patients continuing q 1 Wk or q 2 Wks dosing, whereas the standard would employ a switch to q 4 Wks dosing (Figure 1). Overall compliance dose ratio was consistently above 100%, implying a significant proportion of patients were receiving more frequent dosing than expected under the standard dosing schedule (Figure 2). We carefully evaluated patients in various LOTs and combination therapies. Drug combination was not found to exert a significant impact on the daratumumab dosing pattern. Compliance dose ratio of daratumumab is slightly higher in RRMM compared to the dose ratio in LOT 1 newly diagnosed MM, but even LOT 1 has a ratio greater than 1 (Figure 3). It should be noted that this increased compliance dose ratio is present in all LOT cohorts despite 25% of patients being started on doses less frequent than weekly (Figure 1). CONCLUSIONS In real-world community oncology practices, daratumumab is utilized in a more frequent dosing schedule than the FDA approved standard dosing. With standard dosing there are 23 daratumumab doses in the first 52 weeks. The compliance dose ratio found in our RWD implies 27.3 doses in the first year for the entire cohort and 26.9 and 28.3 doses in LOTs 2 and 3 respectively. Thus, significantly increased drug and administrative costs are incurred over those anticipated in respect to daratumumab dosing utilization. This study is limited to the EMR and administrative claims data of those individuals who are being treated in a community oncology setting. Residual confounding and bias may exist due to entry error and unobserved patient characteristics. References [1] Gergely Varga, et al; Blood 2018; 132:3257 [2] Rifkin R, et al; Clin Ther. 2019;41(5):866-881 [3] DARZALEX® [Prescribing Information] [4] Abdallah N, et al. Ther Adv Hematol. 2019 Dec 23 [5] Rajkumar SV, et al Blood. 2015;126(7):921-922 Disclosures Smith: Integra Connect: Current Employment; Sanofi: Research Funding. Xue:Sanofi: Research Funding; Integra Connect: Current Employment. Marks:Sanofi: Research Funding. Scott:Integra Connect: Current Employment; Sanofi: Research Funding. Blanc:Sanofi: Research Funding. Nagovski:Sanofi: Research Funding. Lambert:Sanofi: Research Funding; Integra Connect: Current Employment. Varughese:Integra Connect: Current Employment; Sanofi: Research Funding.

Gemcitabine and nab-paclitaxel in older adults with metastatic pancreatic cancer: Are two doses per cycle enough?

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 655-655 ◽  
Author(s):  
Arthur Winer ◽  
Elizabeth A. Handorf ◽  
Efrat Dotan
Keyword(s):  
Older Adults ◽  
Pancreatic Cancer ◽  
Real World ◽  
Cox Model ◽  
Performance Status ◽  
Dose Intensity ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
Dosing Schedule

655 Background: The dosing of Gemcitabine and Nab-Paclitaxel (GA), a frontline regimen to treat metastatic pancreatic cancer (mPC), is frequently altered from the traditional dosing schedule (TDS) of day 1, 8, and 15 of a 28 day cycle to a modified dosing schedule (MDS) of 2 doses/cycle. Previous work showed that overall survival (OS) was similar between patients (pts) treated with the MDS vs the TDS. We sought to analyze a larger real-world database to assess these trends. Methods: We retrospectively analyzed de-identified pts with mPC ≥ 65 y/o treated with GA in the Flatiron Health nationwide EHR-derived database. Demographics, treatments (tx), and outcomes were collected. Pts were grouped as either starting with the TDS or MDS. Analysis included time on treatment (TOT) as well as OS. A Cox model was used to test non-inferiority of the MDS vs the TDS for both TOT and OS, adjusting performance status, age, race, gender, and line of therapy (LOT). The upper bound for non-inferiority was a Hazard Ratio (HR) = 1.2. Results: 1497 pts were treated between 1/1/14-5/31/19; 883 pts with the TDS and 614 with the MDS. Median TDS age was 72 (65-85) and MDS was 73 (65-84) (p<0.001). 1237 pts received first- line GA; 60% received the TDS, 40% the MDS. The use of the TDS vs MDS did not vary significantly by LOT, gender, or race, but more pts with a PS of ≥2 received the MDS (p=0.03). In the first-line, outcomes were better for the TDS vs the MDS (unadjusted median TOT 5.3 vs 3.2 mo, p<0.001, OS 9.2 vs 5.3 mo; p<0.001), with consistent results in the ≥ second-line. The MDS did not meet its non-inferiority boundary: first-line TOT HR=1.4 [95% CI 1.2-1.6]; second+ line TOT HR=1.3 [95% CI 1.0-1.7]; first-line OS HR=1.6 [95% CI 1.4-1.8]; second+ line OS HR=1.3 [95% CI 1.0-1.8]. Results were consistent when additionally stratified by PS 0-1 vs 2+. Conclusions: In this large real-world cohort, first-line GA tx with a MDS did not meet criteria for non-inferiority for TOT and OS vs a TDS in older adults with mPC. With the caveats of potential confounding that exist in a de-identified retrospective database, these results suggest that dose intensity may be important in pts with mPC. Further prospective studies are necessary to ensure we utilize effective tx strategies in older adults with mPC.

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