Long-term follow-up of patients (pts) with relapsed or refractory (r/r) follicular lymphoma (FL) treated with copanlisib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7553-7553
Author(s):  
Sirpa Leppä ◽  
Armando Santoro ◽  
Judit Demeter ◽  
George Follows ◽  
Georg Lenz ◽  
...  

7553 Background: The pan-class I phosphatidylinositol 3-kinase inhibitor copanlisib was approved by the FDA in September 2017 for treatment of relapsed FL based on results from the CHRONOS-1 study in pts with indolent non-Hodgkin lymphoma. We report efficacy and safety results of a 2-year (yr) follow-up of FL pts. Methods: Pts with indolent FL (grade [G] 1-3a) r/r to ≥2 prior lines of treatment received copanlisib (60 mg i.v. infusion) on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was objective tumor response rate (ORR) per independent radiologic review (Cheson et al. 2007). Adverse events were reported using MedDRA (v20.1). Data cut-off: February 20, 2018. Results: 104 FL pts were enrolled. Median age was 62 yr (39% >65 yr), the median number of prior lines of anti-cancer therapy was 3 (range 2-8), and 27 pts (26%) were classified as having G3a disease. The ORR was 59%, with complete responses (CR) in 20% ( n=21); 14 pts had a CR at the primary analysis in June 2016. The median duration of response (mDoR) was 12.2 months (mo) (range 0.03-43 mo). Stable disease (SD) was observed in 33% of pts; median duration of SD was 7.8 mo (range 1.3-23 mo). Median progression-free survival (mPFS) was 11.2 mo (range 0.03-44 mo) with 33% alive and progression-free at 2 yrs. Median overall survival (mOS) was 3.2 yr (range 0.06-4.2 yr) with 67% alive at 2 yrs. Median duration of treatment was 26 weeks (wk) (range 1-192 wk); median duration of safety follow-up was 29 wk. In the G3a subset, the ORR was 67% (26% CR), mDoR was 10.9 mo, mPFS was 12.5 mo, and mOS was 2.5 yr. The most common treatment-emergent adverse events occurring in >25% of pts included (all grade/G3+): diarrhea (37%/9%), neutropenia (26%/23%), and pyrexia (28%/5%). Hyperglycemia (49%/40%) and hypertension (29%/23%) were transient. Incidences of pneumonitis (6.7%/1.9%) and colitis (1.0% G4) were low. Conclusions: Long-term follow-up of r/r FL pts treated with copanlisib revealed robust and durable responses with CRs exceeding 20%, including in pts with higher grade disease. The safety profile continues to be both manageable and favorable, with no evidence of late-onset severe toxicities. Clinical trial information: NCT01660451.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
Fritz Offner ◽  
Tadeusz Robak ◽  
Ann Janssens ◽  
Govind Babu Kanakasetty ◽  
Janusz Kloczko ◽  
...  

7528 Background: Previously in the COMPLEMENT 1 study, treatment with OFA and CHL in pts with untreated CLL had shown a significant improvement in the progression-free survival (PFS) compared with CHL alone, and was well tolerated. Here, we report the final overall survival (OS) analysis of the 5-year (y) follow-up, updated investigator-assessed PFS and safety from the study. Methods: Untreated pts, not fit for fludarabine-based therapy (due to advanced age or co-morbidities) were randomized 1:1 to OFA+CHL or CHL alone. Pts in OFA+CHL arm received OFA (Cycle 1: 300 mg day (d) 1, 1000 mg d8; subsequent cycles: 1000 mg d1) in addition to CHL (10 mg/m2, d1-7) for 3 to 12 cycles of 28 d each. Pts in CHL arm received CHL only. Results: Overall, 447 pts were randomized to OFA+CHL (n = 221) or CHL (n = 226); 168 (76%) and 164 (73%) pts completed the scheduled treatments, respectively. Baseline characteristics were similar in both arms. The investigator-assessed median PFS was 23.4 months (mos) in the OFA+CHL arm and 14.7 mos in the CHL arm (HR: 0.61 [95% CI 0.49, 0.76], p < 0.001). Median OS could not be estimated for the OFA+CHL arm and was 84.7 mos for the CHL arm (HR: 0.88 [95% CI 0.65, 1.17], p = 0.363). Estimated OS rate (95% CI) at 5 y was 68.5% (61.5%, 74.5%) in the OFA+CHL arm, and 65.7% (58.6%, 71.9%) in the CHL arm. Post-treatment anti-cancer therapy after discontinuation was received by a greater proportion of pts in the CHL (66%) vs. OFA+CHL (56%), and started earlier in the CHL arm (486 d) vs. OFA+CHL (743 d) arm. Overall, 84 (39%) pts in the OFA+CHL, and 99 (44%) pts in the CHL arms died during the study with 5 on-treatment deaths in each group. Grade ≥3 adverse events were seen in 64% and 48% of pts in the OFA+CHL vs. CHL arms, respectively, most common being (≥5% in either arm) neutropenia (26% vs. 15%), thrombocytopenia (5% vs. 10%), pneumonia (9% vs. 5%), and anemia (5% vs. 5%). Conclusions: This 5-y survival follow-up analysis supported the results from primary analysis with an estimated 12% (not significant) and 39% risk reduction in OS and PFS, respectively, in the OFA+CHL arm compared with the CHL arm. No new safety concerns were observed in the OFA+CHL arm. Clinical trial information: NCT00748189.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9071-9071
Author(s):  
Scott N. Gettinger ◽  
Rudolf M. Huber ◽  
Dong-Wan Kim ◽  
Lyudmila Bazhenova ◽  
Karin Holmskov Hansen ◽  
...  

9071 Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30–300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (̃67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (̃53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573. [Table: see text]


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 617-617 ◽  
Author(s):  
Robert J. Motzer ◽  
Scott S. Tykodi ◽  
Bernard Escudier ◽  
Stephane Oudard ◽  
Hans J. Hammers ◽  
...  

617 Background: CheckMate 025 demonstrated superior overall survival (OS) in previously treated patients (pts) with aRCC, with improved safety and tolerability in the NIVO arm compared with EVE. The primary analysis was based on 14-months minimum follow-up. Here, we report an updated, final analysis with an extended minimum follow-up of 64 months. Methods: Previously treated pts with predominantly clear cell aRCC were randomized (1:1) to NIVO 3 mg/kg IV every 2 weeks or EVE 10 mg orally once daily until progression or unacceptable toxicity. The primary endpoint was OS. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and safety. Confirmed ORR and PFS were per investigator (inv) using RECIST v1.1. Results: Overall, 410 vs 411 pts were randomized to NIVO vs EVE, respectively. OS benefit was maintained and PFS favored NIVO vs EVE with long-term follow-up (HR 0.84 (95% CI 0.72–0.99). (Table) ORR was higher (23% vs 4%) with NIVO vs EVE and median duration of response (DOR) was longer (18.2 vs 14.0 months). Ongoing response was observed in 28% vs 18% of pts with NIVO vs EVE. Most pts received subsequent systemic anticancer therapy: 276 pts in the NIVO arm (67%; most commonly EVE [35%] or axitinib [33%]) and 296 pts in the EVE arm (72%; most commonly axitinib [41%] or NIVO [26%]). No new safety signals or treatment-related deaths emerged with long-term follow-up in either arm. More pts in the EVE arm (37%) experienced a grade 3/4 treatment-related AE compared with pts in the NIVO arm (21%). Conclusions: At >5-years minimum follow-up, response rates and survival remain superior with NIVO vs EVE, and 28% of responses to NIVO are ongoing. Long-term follow-up highlights the efficacy and safety of NIVO monotherapy in pts with aRCC. Clinical trial information: NCT01668784. [Table: see text]


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 269-269
Author(s):  
Anthony B. El-Khoueiry ◽  
Thomas Yau ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
Armando Santoro ◽  
...  

269 Background: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) followed by NIVO 240 mg Q2W is approved in the US for sorafenib-treated pts with aHCC based on initial results from CheckMate 040 (NCT01658878), which reported objective response rate (ORR) of 32% and median overall survival (mOS) of 22.8 months (mo).1 We present 44-mo long-term follow-up results from the CheckMate 040 NIVO+IPI cohort. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Safety and tolerability, ORR (blinded independent central review per RECIST v1.1), duration of response (DOR), disease control rate (DCR), and OS were assessed. Data cutoff was May 26, 2020. Results: 148 pts were randomized. Minimum follow-up was 44 mo. mOS remained at 22.2 mo in arm A, 12.5 mo in arm B, and 12.7 mo in arm C; 36-mo OS rates were 42%, 26%, and 30%, respectively. Durable responses were achieved across treatment arms, with DOR approaching 4 years in some cases. DCR was higher in arm A than arms B and C. In all arms, responses were observed regardless of baseline programmed death ligand 1 expression ( < 1% or ≥ 1%) or baseline alpha-fetoprotein level ( < 400 µg/L or ≥ 400 µg/L). Pts with hepatitis B or C virus (HBV or HCV) etiology had higher ORR than uninfected pts in arms B (29% vs 43% vs 9%) and C (31% vs 42% vs 0%). ORR was independent of etiology in arm A (HBV, 32%; HCV, 29%; uninfected, 31%). Additional efficacy data are in the table. There were no additional discontinuations due to treatment-related adverse events or immune-mediated adverse events (IMAEs) since the primary analysis. IMAEs were reported more frequently in arm A than arms B and C; the most common were rash, hepatitis, and adrenal insufficiency. Most IMAEs were reversible and resolved when treated using established algorithms. Conclusions: At a minimum follow-up of 44 mo, second-line NIVO1+IPI3 continued to demonstrate clinically meaningful responses and long-term survival benefit in aHCC. The safety profile was manageable and no new safety signals were identified with longer follow-up. Clinical trial information: NCT01658878. [Table: see text]


2021 ◽  
Author(s):  
Ming Zhao ◽  
Xiangping Fu ◽  
Zhiwen Zhang ◽  
Anmin Li ◽  
Xiaopeng Wang ◽  
...  

Abstract Objective The intracranial brachytherapy has been applied for decades, however, no results with long-term follow-up have been reported. This study investigated the long-term efficiency of intra-tumoral injection of 131I-chTNT in patients with deep-seated glioma. Method Thirty-five patients undergoing 131I-chTNT brachytherapy between December 2004 and May 2009 were enrolled. 131I-chTNT was injected at a dose of 1.5 mCi/cm3 at an interval of 1 month for consecutive 3 times. Serial ECT scan and MRI were performed during follow-up. Progression-free survival (PFS) and overall survival (OS) were analyzed. Adverse reactions were graded with WHO Toxicity Grading Scale for determining the severity of adverse events. Results ECT scan showed that enhanced accumulation of radioactive agents in the tumor lasted for more than 30 days. Three months after final injection, tumor complete remission (CR) was observed in 4 patients (11.4 %), partial remission (PR) in 11 cases (31.4 %), stable disease (SD) in 10 cases (28.6 %) and progressive disease (PD) in 10 cases (28.6 %). At 6-month, CR, PR, SD and PD were 2, 6, 12 and 15 respectively. After 10 years of follow-up, median progression-free survival (PFS) and overall survival (OS) were 5.4 and 11.4 months. One-year survival was 45.7 %, two and five-year survival was 8.6 %, ten-year survival was 5.7 %. Multivariate analysis showed that pathological grade and tumor diameter were independent prognostic factors for PFS and OS. Grade I–II adverse events occurred after drug injection, including nausea, fever, headache, hairloss and fatigue. Conclusion 131I-chTNT intracranial brachytherapy is efficient and safe for patients with deep-seated glioma. It is a reliable option for inoperable glioma patients.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.2-1227
Author(s):  
E. Berard ◽  
T. Barnetche ◽  
L. Rouxel ◽  
C. Dutriaux ◽  
L. Dousset ◽  
...  

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared


Author(s):  
Simo S. A. Miettinen ◽  
Hannu J. A. Miettinen ◽  
Jussi Jalkanen ◽  
Antti Joukainen ◽  
Heikki Kröger

Abstract Introduction This retrospective study investigated the long-term follow-up results of medial opening wedge high tibial osteotomy (MOWHTO) with a pre-countered non-locking steel plate implant (Puddu plate = PP) used for medial knee osteoarthrosis (OA) treatment. Materials and methods Consecutive 70 MOWHTOs (66 patients) were performed between 01.01.2004 and 31.12.2008 with the mean follow-up time of 11.4 (SD 4.5; range 1.2–16.1) years. The Kaplan–Meier survival analysis was used to evaluate the cumulative survival of the implant in terms of age (< 50 years old and ≥ 50 years old) and gender. Adverse events were studied and Cox regression analysis was used to evaluate risk factors [age, gender, body mass index (BMI), preoperative mechanical axis, severity of OA, use of bone grafting or substitution and undercorrection of mechanical axis from varus to valgus] for revisions. Results The estimates for the cumulative survival with no need for TKA after MOWHTO were 86% at 5 years, 67% at 10 years and 58% at 16.1 years (SE 0.6, CI 95% 11.1–13.5). A total of 33/70 (47%) adverse events occurred and 38/70 (54%) knees required some revision surgery during the follow-up. Cox regression did not show any statistically significant risk factors for revision. Conclusions The PP has feasible MOWHTO results with a cumulative survival of 67% at 10 years with no need for conversion to TKA. Many adverse events occurred and revision rate due to any reason was high. Age or gender did not have statistically significant differences in terms of survival.


2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.


1983 ◽  
Vol 70 (12) ◽  
pp. 740-743 ◽  
Author(s):  
A. J. Hedley ◽  
P. D. Bewsher ◽  
S. J. Jones ◽  
A. S. M. Khir ◽  
P. Clements ◽  
...  

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