scholarly journals Subcutaneous daratumumab in Asian patients with heavily pretreated multiple myeloma: subgroup analyses of the noninferiority, phase 3 COLUMBA study

2021 ◽  
Vol 100 (4) ◽  
pp. 1065-1077
Author(s):  
Shinsuke Iida ◽  
Takayuki Ishikawa ◽  
Chang Ki Min ◽  
Kihyun Kim ◽  
Su Peng Yeh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Geometric Mean ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Phase 3 ◽  
Asian Patients ◽  
Patient Reported ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Asian Cohort

AbstractThe phase 3 COLUMBA study demonstrated noninferiority of subcutaneous daratumumab (DARA SC) to intravenous daratumumab (DARA IV) in relapsed or refractory multiple myeloma. We present a subgroup analysis of Asian patients from COLUMBA. Eligible patients had ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were double refractory. Co-primary endpoints were overall response rate (ORR) and maximum trough concentration (Ctrough). Secondary endpoints included rates of infusion-related reactions, progression-free survival, and patient-reported satisfaction with therapy. Sixty-seven Asian patients (DARA SC, n = 30; DARA IV, n = 37) were randomized, including 42 Japanese patients (DARA SC, n = 18; DARA IV, n = 24). Comparable ORRs for DARA SC versus DARA IV were seen in the Asian cohort (66.7% vs 43.2%) and Japanese-only cohort (61.1% vs 54.2%), including patients weighing ≤ 65 kg. Similarity of Ctrough was seen in both Asian and Japanese-only cohorts; the ratio of the geometric mean of the Ctrough concentrations for DARA SC/DARA IV was 143.96% (90% confidence interval (CI), 112.03–185.00%) and 148.02% (90% CI, 113.32–193.34%), respectively. The Asian cohort (both treatment groups) and Japanese-only cohort (DARA SC group) experienced higher rates of grade 3/4 cytopenias compared with the global COLUMBA population, occurring predominantly in patients of low bodyweight; no patients discontinued treatment due to cytopenias. The Cancer Therapy Satisfaction Questionnaire results generally favored DARA SC. In the Asian and Japanese-only cohorts, DARA SC was comparable to DARA IV. The efficacy, pharmacokinetic, safety, and satisfaction results were generally consistent with the global COLUMBA population regardless of patient bodyweight. ClinicalTrials.gov Identifier: NCT03277105

scholarly journals Daratumumab plus bortezomib, melphalan, and prednisone in East Asian patients with non-transplant multiple myeloma: subanalysis of the randomized phase 3 ALCYONE trial

2019 ◽  
Vol 98 (12) ◽  
pp. 2805-2814 ◽  
Author(s):  
Tomoaki Fujisaki ◽  
Takayuki Ishikawa ◽  
Hiroyuki Takamatsu ◽  
Kenshi Suzuki ◽  
Chang-Ki Min ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
East Asian ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Similar Efficacy ◽  
Korean Patients ◽  
Asian Patients ◽  
Grade 3 ◽  
East Asian Patients

Abstract In the ALCYONE trial, daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) reduced the risk of disease progression or death by 50% versus bortezomib, melphalan, and prednisone (VMP) in patients with transplant-ineligible newly diagnosed multiple myeloma. Here, we report a subanalysis of East Asian patients from ALCYONE. After a median follow-up of 17.1 and 15.9 months for Japanese (n = 50) and Korean (n = 41) patients, respectively, median progression-free survival for D-VMP versus VMP was not reached (NR) versus 20.7 months in Japanese patients and NR versus 14.0 months in Korean patients. The overall response rate for D-VMP versus VMP was 96% versus 92% in Japanese patients and 91% versus 61% in Korean patients. Using next-generation sequencing, minimal residual disease negativity at 10−5 sensitivity for D-VMP versus VMP was 33% versus 8% among Japanese patients and 17% versus 0% among Korean patients. Rates of any grade and grade 3/4 pneumonia were consistent with the rates observed for the global safety population. Similar efficacy and safety findings were observed in the combined Japanese and Korean subgroup and ≥ 75 years of age subgroup. In conclusion, D-VMP was safe and efficacious in East Asian patients, consistent with the global ALCYONE population.

scholarly journals Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

2020 ◽  
pp. JCO.20.02259
Author(s):  
Paul G. Richardson ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Bladé ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

Phase 1 Study of the Investigational Proteasome Inhibitor Ixazomib Alone or in Combination with Lenalidomide–Dexamethasone (Rd) in Japanese Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5752-5752 ◽  
Author(s):  
Hiroshi Handa ◽  
Kenshi Suzuki ◽  
Takaaki Chou ◽  
Takafumi Matsushima
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Research Funding ◽  
Phase 1 ◽  
Single Agent ◽  
Japanese Patients ◽  
M Protein ◽  
Phase 3 ◽  
Grade 3 ◽  
Ongoing Phase

Background Ixazomib is the first oral proteasome inhibitor to be investigated clinically for the treatment of MM. Phase 1 studies have shown single-agent activity and manageable toxicities in RRMM (Kumar et al. Blood 2014) and phase 1/2 studies have suggested the feasibility and activity of weekly oral ixazomib plus Rd in previously untreated MM (Kumar et al. ASH 2012; Richardson et al. ASH 2013). These findings have led to ongoing phase 3 trials of weekly ixazomib 4 mg + Rd in RRMM and previously untreated MM. However, the early-phase studies were conducted in Western pts. This phase 1, open-label multicenter study aimed to determine the safety, tolerability, and pharmacokinetics (PK) of weekly ixazomib alone or with Rd in Japanese pts with RRMM (Japic Clinical Trials Information no. 121822). Methods Primary objectives were to evaluate the safety and tolerability, including dose-limiting toxicities (DLTs) and adverse events (AEs), and the PK of ixazomib alone or with Rd. A secondary objective was evaluation of antitumor activity. Japanese pts aged ≥20 years with RRMM who had received at least 2 prior regimens, which must have included bortezomib, thalidomide or lenalidomide, and corticosteroids, were eligible. All had measurable disease and ECOG performance status of 0–2. Pts with grade ≥2 peripheral neuropathy or grade ≥2 diarrhea at study entry were excluded. Pts received ixazomib 4 mg on days 1, 8, and 15 of 28-day cycles, alone or with Rd (lenalidomide 25 mg on days 1–21, dexamethasone 40 mg on days 1, 8, 15, and 22), per the regimen used in the ongoing phase 3 trials. AEs were graded per NCI-CTCAE v4.03. Blood samples for PK analysis were taken at multiple time points prior to and after dosing on days 1 and 15 of cycle 1. Responses were assessed per IMWG uniform response criteria. Results Fourteen pts were enrolled; 8 (57%) were male, median age was 62.5 yrs (range 53–71), 4 pts were aged ≥65 yrs, median number of prior therapies was 7. Seven pts received single-agent ixazomib and 7 received ixazomib + Rd. One pt in each cohort was excluded from the DLT-evaluable population. Two patients experienced DLTs in cycle 1: 1 pt receiving single-agent ixazomib had grade 4 thrombocytopenia and grade 3 diarrhea, hypertension, hypokalemia, hyponatremia, and nausea; 1 pt in the ixazomib + Rd cohort had grade 4 thrombocytopenia and neutropenia. All events were considered treatment-related. At data cut-off (Jan 6 2014), 6 pts remained on treatment and 8 had discontinued due to: progressive disease (PD; n=3), AEs (n=3), symptomatic deterioration, and protocol violation (each n=1). At data cut-off, pts (n=14) had received a median of 6 cycles of ixazomib (range 1–21); the 7 pts in the ixazomib + Rd cohort had received a median of 4 cycles (range 1–12) of ixazomib + Rd. Thirteen (93%) pts experienced treatment-related AEs; the most common were neutropenia (71%), thrombocytopenia (71%), leukopenia (64%), lymphopenia (57%), and diarrhea (50%). There were no cases of peripheral neuropathy. Nine (64%) pts had grade ≥3 AEs; the most common were lymphopenia (50%), neutropenia (43%), and thrombocytopenia (36%). Two (14%) pts (single-agent cohort) had serious AEs (grade 2 bronchitis in 1 pt, and grade 4 thrombocytopenia and grade 3 hypokalemia in 1 pt). Three pts discontinued due to AEs; 1 due to diarrhea in the single-agent cohort, and 1 due to neutropenia and 1 due to thrombocytopenia in the ixazomib + Rd cohort. There were no deaths. PK data showed ixazomib was rapidly absorbed with a Tmax at 1.08–1.83 hrs. Terminal half-life (geometric mean) was 5.7 days for single-agent ixazomib and 5.2 days for ixazomib + Rd. There were no substantial differences in the ixazomib PK profile between the two cohorts. Thirteen pts were response-evaluable. One pt (ixazomib + Rd cohort) had a partial response; at data cut-off, this pt remained in response with a 100% M-protein reduction (unconfirmed VGPR) and duration of response of ~10.8 months. Seven pts had stable disease (including 3 with M-protein reductions of 25–50%), 2 had PD, and 3 were not assessable. Conclusions These data suggest that ixazomib 4 mg alone or with Rd is feasible and tolerable in Japanese pts with RRMM. The AEs were manageable, reflecting the AE profile seen in Western populations, supporting the use of this dose and schedule in Japanese pts. Disclosures Handa: Celgene: Research Funding; Yakult: Research Funding; Kirin: Research Funding; Chugai: Research Funding. Off Label Use: Investigational agent ixazomib for the treatment of Japanese patients with relapsed and/or refractory multiple myeloma.. Matsushima:Takeda Pharmaceutical Company Limited : Employment.

Subgroup analyses of Japanese patients from the PREVAIL trial of enzalutamide (ENZA) in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 265-265 ◽  
Author(s):  
Go Kimura ◽  
Junji Yonese ◽  
Takashi Fukagai ◽  
Tomomi Kamba ◽  
Kazuo Nishimura ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Geometric Mean ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Risk Of Death ◽  
Hazard Ratios ◽  
Grade 3

265 Background: In PREVAIL, an international phase 3 randomized trial, treatment with ENZA decreased the risk of radiographic progression or death by 81% and the risk of death by 29% compared with placebo. We evaluated efficacy, safety and pharmacokinetic exposure with ENZA in the Japanese subgroup of patients participating in PREVAIL. Methods: Asymptomatic or mildly symptomatic chemotherapy-naïve patients with mCRPC progressing on androgen deprivation therapies were randomized 1:1 to ENZA 160 mg or placebo until discontinuation upon radiographic progression or initiation of chemotherapy. Continued androgen-deprivation therapy was required. Coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS). Prostate-specific antigen (PSA) response was defined as a confirmed ≥50% reduction from baseline to nadir. Results: A total of 1,717 patients (ENZA: 872, placebo: 845) were randomized in PREVAIL, of which 61 patients were Japanese (ENZA: 28, placebo: 33). The trial was halted after a planned interim analysis at which hazard ratios calculated for OS (0.71; 95%CI: 0.60-0.84) and rPFS (0.19; 95%CI: 0.15-0.23) showed significant benefit of ENZA vs placebo. Hazard ratios for OS and rPFS in Japanese patients were 0.60 (95%CI: 0.20-1.78) and 0.29 (95%CI: 0.030-2.95), respectively. Time to chemotherapy was delayed from a median 10 months on placebo vs not yet reached on ENZA, with a hazard ratio of 0.46 (95%CI: 0.22-0.96). PSA responses were more common in Japanese patients receiving ENZA (61%) vs placebo (21%) (treatment effect = 39.5%; 95%CI: 16.7%-62.3%). Plasma concentration of ENZA was slightly higher in the Japanese subgroup: geometric mean Cmin= 13.8 µg/mL vs 12.3 µg/mL in the non-Japanese cohort at 13 weeks. In the Japanese subgroup adverse events (AEs) ≥ Grade 3 were reported by 9/28 patients (32%) on ENZA vs 13/33 patients (39%) on placebo. Treatment-related AEs ≥ Grade 3 were rare: in the ENZA arm (1/28; 3.6%) and in the placebo arm (2/33; 6.1%). Conclusions: Theefficacy and safety results in the Japanese subgroup were generally consistent with the overall results from the PREVAIL trial. Clinical trial information: NCT01212991.

Interim analysis results of surufatinib in U.S. patients with neuroendocrine tumors (NETs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4114-4114
Author(s):  
Andrew Scott Paulson ◽  
Daneng Li ◽  
Max W. Sung ◽  
Christopher Tucci ◽  
John S. Kauh ◽  
...  
Keyword(s):  
Safety Profile ◽  
Tyrosine Kinases ◽  
Phase 1 ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Phase 3 ◽  
Heavily Pretreated ◽  
Grade 3

4114 Background: Surufatinib (S) is a targeted inhibitor of tyrosine kinases VEGFR1, 2, and 3; FGFR1; and CSF-1R. A manageable safety profile and statistically significant efficacy of S have previously been demonstrated in patients (pts) with advanced NETs of extrapancreatic (epNET) and pancreatic (pNET) origin in 2 phase 3 randomized trials conducted in China (SANET-ep, NCT02588170; SANET-p, NCT02589821). Pts with epNETs achieved a median progression free survival (PFS) of 9.2 v 3.8 months (mo) (hazard ratio [HR] 0.334; p < 0.0001), and pts with pNETs achieved a median PFS of 10.9 v 3.7 mo (HR 0.491; p = 0.0011), with S v placebo, respectively. S has recently been approved for the treatment (tx) of pts with epNETs in China. Methods: A phase 1, dose escalation (ESC)/expansion (EXP) trial was conducted to evaluate and confirm the efficacy and safety of S in US pts. ESC was completed, and the maximum tolerated dose and recommend phase 2 dose were determined to be 300 mg, same as previous trials. The EXP completed enrollment of the epNET and pNET cohorts, and the primary endpoint was investigator-assessed PFS rate at 11 mo. Secondary objectives included assessment of safety and PK. Results: 32 pts with heavily pretreated progressive NETs (16 epNET and pNET each) were enrolled in the dose EXP. The median age was 62.2 years (44-75) and 64.4 years (39-72) for epNET and pNET pts, respectively. 65.6% of pts received ≥3 prior lines of tx (median lines of therapy: epNET: 2 [2-5]; pNET: 4 [1-8]), and all pts previously received everolimus and/or sunitinib. As of the data cutoff of 30-Jun-20, 7 pts remained on tx (4 epNET; 3 pNET). The median number of tx cycles was 8.0 (2, 15) for epNET and 8.5 (2, 23) for pNET pts. The PFS rate at 11 mo was 51.1% (95% confidence interval [CI]: 12.8, 80.3) for pts with epNETs and 57.4% (95% CI: 28.7, 78.2) for pts with pNETs. The observed mPFS was 11.50 mo (95% CI: 6.47, 11.50) and 15.18 mo (95% CI: 5.19, NR) for pts with epNETs and pNETs, respectively. An objective response rate (ORR) of 6.3% was observed for pts with epNETs and 18.8% for pts with pNETs. A disease control rate of 90.6% (95% CI: 75.0, 98.0) was observed for all NET pts (93.8% epNET; 87.5% pNET). The safety profile of S remains consistent with previously completed trials. All pts (n = 32) had reported at least 1 adverse event (AE), and 24 pts (75%) reported AEs ≥grade 3. The most common AEs of any grade reported were fatigue (46.9%), hypertension (43.8%), proteinuria (37.5%), diarrhea (34.4%), vomiting (28.1%), and nausea (25.0%). The most commonly reported AEs ≥grade 3 ( > 5%) were hypertension (37.5%); diarrhea (9.4%); and proteinuria, dysphagia, and anemia (6.3% each). AEs leading to tx discontinuation occurred in 21.9% of pts. Conclusions: S has demonstrated antitumor activity in heavily pretreated US pts with progressive NETs with a manageable safety profile that is consistent with 2 completed phase 3 studies. S continues to be studied in other ongoing clinical trials globally. Clinical trial information: NCT02549937.

MM-011: A Phase 2 Study of Pomalidomide Plus Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma in Japan

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5374-5374
Author(s):  
Shotaro Hagiwara ◽  
Shinichiro Okamoto ◽  
Kosei Matsue ◽  
Shinsuke Iida ◽  
Kazutaka Sunami ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Response Rate ◽  
Study Drug ◽  
Japanese Patients ◽  
Company Limited ◽  
Phase 2 Study ◽  
Common Grade ◽  
Heavily Pretreated ◽  
Grade 3

Abstract Introduction: Pomalidomide plus low-dose dexamethasone (POM + LoDEX) is approved for the treatment of patients with relapsed and refractory multiple myeloma (RRMM). In RRMM, POM + LoDEX significantly prolonged progression-free survival (PFS) compared with POM alone (MM-002; Richardson et al Blood, 2014) and significantly improved PFS and overall survival (OS) compared with high-dose DEX alone (MM-003; San Miguel et al Lancet Oncol, 2013), while demonstrating an acceptable safety profile. In Japanese patients with RRMM, a phase 1 study identified POM 4 mg/day as the tolerated dose (MM-004; Iida ASH 2014), consistent with observations in Caucasian patients. The study presented here, MM-011, was conducted to evaluate the efficacy and safety of POM + LoDEX in Japanese patients with RRMM. Methods: MM-011 was a multicenter, single-arm, open-label phase 2 study in patients with RRMM. Eligible patients had received ≥ 2 prior therapies, including ≥ 2 cycles of lenalidomide and ≥ 2 cycles of bortezomib (either separately or in combination) and had developed progressive disease on or within 60 days of the last prior therapy. Patients received POM 4 mg orally on days 1-21, and LoDEX orally on days 1, 8, 15, and 22 of each 28-day cycle. LoDEX was given at 40 or 20 mg in patients aged ≤ 75 or > 75 years, respectively. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was overall response rate (ORR; partial response rate [PR] or better) of POM + LoDEX according to the International Myeloma Working Group criteria. The required sample size was calculated using the expected response rate of 25%, the threshold response rate of 10% on 1-sided alpha of 0.05, and the statistical power of 80% based on the test for 1 sample proportion. Thirty-three pts were needed as a result of this calculation. Results: A total of 36 patients were enrolled. Median age was 64.5 years (range, 43-78 years), and 11% were aged > 75 years. Patients had a high tumor burden (81% had Durie-Salmon stage II or III disease) and were heavily pretreated (median of 6.5 prior anti-myeloma regimens; range, 2-15 regimens). All but 1 patient (97%) were refractory to lenalidomide and 58% were refractory to both lenalidomide and bortezomib. At the data cutoff (February 3, 2015), 16 patients (44%) remained on treatment. Disease progression was the most common reason for discontinuation (n = 14; 39%). All 36 patients enrolled were evaluable for efficacy. The ORR was 42% (n = 15 [95% CI, 26%-58%]), including complete response in 3% (n = 1) and PR in 39% (n = 14). Median PFS was 10.2 months (median follow-up, 4.6 months), and median OS was not reached (median follow-up, 7.7 months). In the 15 responders, median time to response was 1.9 months and median duration of response was not reached. The most common grade 3/4 hematologic adverse events (AEs) were neutropenia (n = 23; 64%), anemia (n = 15; 42%), and thrombocytopenia (n = 11; 31%), and the most common grade 3/4 non-hematologic AEs were pneumonia (n = 3; 8%) and decreased appetite (n = 3; 8%). Peripheral neuropathy (any grade) occurred in 8% (n = 3). No deep vein thrombosis or pulmonary embolism was reported. Overall, AEs were similar to those in other POM studies, and no new significant AEs were reported in Japanese RRMM patients. Three patients (8%) had an AE that led to discontinuation. Three patients died on study (or within 28 days of the last dose of study drug). Two of these patients died due to multiple myeloma and 1 due to AE (asthma and pneumonia, suspected to be related to study drug). Conclusions: POM + LoDEX is an effective regimen in heavily pretreated Japanese patients with RRMM with acceptable safety profiles that are comparable with those of POM studies in RRMM in other regions. Disclosures Hagiwara: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Matsue:Celgene Corporation: Honoraria. Iida:Celgene Corporation: Honoraria, Research Funding; Janssen Pharmaceuticals Inc: Honoraria; Kyowa Hakko Kirin Inc: Research Funding; Ono Pharmaceutical Inc: Research Funding; Chugai Pharmaceutical Co: Research Funding; Eli Lilly Inc: Research Funding. Sunami:Ono Pharmaceutical Company, Limited: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding. Ando:Kyowa Hakko Kirin Co., Ltd: Research Funding. Tobinai:Gilead Sciences: Research Funding. Chou:Celgene Corporation: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Ono Pharmaceutical CO., LTD.: Consultancy, Honoraria. Kaneko:Celgene Corporation: Research Funding. Uemura:Celgene Corporation: Employment. Tamakoshi:Celgene Corporation: Employment. Zaki:Celgene Corporation: Employment, Equity Ownership. Doerr:Celgene Corporation: Employment.

Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 772-778 ◽  
Author(s):  
Paul Richardson ◽  
Sundar Jagannath ◽  
Mohamad Hussein ◽  
James Berenson ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Prior Treatment ◽  
Once Daily ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Treatment Regimens ◽  
Common Grade ◽  
Grade 3

Abstract Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351.

Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Joyce O'Shaughnessy ◽  
Kevin Punie ◽  
Mafalda Oliveira ◽  
Filipa Lynce ◽  
Sara M. Tolaney ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Antibody Drug Conjugate ◽  
Phase 3 ◽  
Chemotherapy Agent ◽  
Recist 1.1 ◽  
Duration Of Response ◽  
Grade 3

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

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