Efficacy of mogamulizumab in previously treated patients with less advanced mycosis fungoides: Results from the MAVORIC study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19031-e19031
Author(s):  
Larisa J. Geskin ◽  
Julia Scarisbrick ◽  
Martine Bagot ◽  
David Christopher Fisher ◽  
Craig Elmets ◽  
...  
Keyword(s):  
Mycosis Fungoides ◽  
Systemic Therapy ◽  
Radiation Treatment ◽  
Response Rates ◽  
Disease Stage ◽  
Topical Steroids ◽  
Post Hoc Analysis ◽  
Stage Ib ◽  
Previously Treated ◽  
Post Hoc

e19031 Background: In the MAVORIC Phase 3 study, patients (pts) with previously treated mycosis fungoides (MF)/Sezary syndrome (SS) stage IB-IVB who received mogamulizumab (MOGA) had significantly prolonged progression-free survival and greater overall response rates (ORR) compared to pts on vorinostat (VORI) (Kim et al. Lancet Oncol 2018). Less advanced MF (stage IB/IIA) is a chronic skin malignancy that can involve blood and nodes and may require many lines of systemic therapy over the disease course. This post-hoc analysis specifically examined efficacy and safety of the recently approved MOGA in stage IB/IIA MF pts. Methods: In MAVORIC, stage IB-IVB MF/SS pts who were treated with ≥1 prior systemic therapy were randomized to MOGA or oral VORI. In the post-hoc analysis, time to next treatment (TTNT) was defined as time to any therapy excluding topical steroids or focal radiation treatment. ORR was based on global composite response in 4 disease compartments – skin, blood, lymph nodes, and viscera – achieved at 2 consecutive visits at least 8 weeks apart. Individual compartment responses were also assessed. Results: A total of 85 pts with stage IB/IIA MF were included (MOGA, IB n = 15, IIA n = 21; VORI, IB n = 27, IIA n = 22). Overall, 24% (10/42) of IB pts and 28% (12/43) of IIA pts had received ≥6 prior therapies. Median TTNT with MOGA in IB pts was 11.5 months (mo) (95% CI, 1.4,16.0) compared to 3.1 mo (95% CI, 2.7, 5.3) with VORI; in IIA pts, median TTNT was 10.1 mo (95% CI, 5.5, 12.6) and 4.9 mo (95% CI, 2.4, 8.0), respectively. ORR in IB pts receiving MOGA and VORI was 20% (3/15) and 18.5% (5/27), respectively; ORR in IIA was 19% (4/21) and 0% (0/22), respectively. With respect to stage IB and IIA, compartmental response rates with MOGA were: skin (20% [3/15], 38% [8/21]), blood (0% [0/2], 75% [6/8]), and lymph node (0% [0/0], 15% [3/20]), respectively. Adverse events were generally manageable and consistent with the ITT population. Conclusions: Though MAVORIC was not powered to determine treatment effect by disease stage, this post-hoc analysis of TTNT, ORR, and compartmental response in stage IB/IIA demonstrates meaningful clinical benefit with MOGA in previously treated, less advanced MF pts. Clinical trial information: NCT01728805.

Time to next treatment in patients with previously treated cutaneous T-cell lymphoma (CTCL) receiving mogamulizumab or vorinostat: A MAVORIC post-hoc analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7539-7539 ◽  
Author(s):  
Barbara Pro ◽  
Youn H. Kim ◽  
Pablo L. Ortiz-Romero ◽  
Lubomir Sokol ◽  
Julia Scarisbrick ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Progression Free Survival ◽  
Disease Type ◽  
Disease Stage ◽  
Topical Steroids ◽  
Additional Measure ◽  
Post Hoc Analysis ◽  
Stage Grouping ◽  
Previously Treated ◽  
Post Hoc

7539 Background: CTCLs are chronic skin malignancies, characterized by relapsing/remitting behavior and progressive resistance to treatments, with a reported median time to next treatment (TTNT; ie, systemic treatment excluding topical steroids) in mycosis fungoides (MF) and Sezary syndrome (SS) of 5.4 months (mo) (Hughes et al. Blood, 2015). The phase 3 MAVORIC study demonstrated mogamulizumab (MOGA) was superior to vorinostat (VORI) in progression-free survival (median 7.7 vs 3.1 mo, P<0.0001) and confirmed overall response rates (28% vs 4.8%, P<0.0001) in previously treated patients with MF/SS (Kim et al. Lancet Oncol 2018). This post-hoc analysis examines TTNT to further explore the patient clinical experience. Methods: Patients with MF/SS who were treated with ≥1 prior systemic therapy were randomized 1:1 to receive MOGA (1.0 mg/kg, administered once weekly for the first 28-day cycle, then on Days 1 and 15 of subsequent cycles) or oral VORI (400 mg daily). Patients on VORI were permitted to crossover to MOGA upon approval. TTNT was defined as time to any therapy excluding topical steroids or focal radiation. The length of TTNT was assessed overall and by disease stage grouping (IB/II and III/IV) and disease type (MF and SS). Results: Median TTNT for the full ITT population was longer with MOGA at 11 mo (95% CI, 8.8-12.6) compared to VORI at 3.5 mo and consistently longer for MOGA vs VORI across disease stage grouping or by disease type (Table). Conclusions: TTNT in MF/SS represents an additional measure of clinical benefit and disease control in patients who may have progressed based on strict protocol definitions of progression. This post hoc analysis showing a prolonged TTNT across disease stages and types supports a clinical benefit for MF and SS patients who receive MOGA. Clinical trial information: NCT01728805. [Table: see text]

scholarly journals Post hoc Analysis of a Randomized, Controlled, Phase 2 Study to Assess Response Rates with Chlormethine/Mechlorethamine Gel in Patients with Stage IA–IIA Mycosis Fungoides

Dermatology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Christiane Querfeld ◽  
Julia J. Scarisbrick ◽  
Chalid Assaf ◽  
Emmanuella Guenova ◽  
Martine Bagot ◽  
...  
Keyword(s):  
Contact Dermatitis ◽  
Adverse Events ◽  
Clinical Response ◽  
Mycosis Fungoides ◽  
Response Rates ◽  
Treatment Frequency ◽  
Post Hoc Analysis ◽  
Randomized Controlled ◽  
Stage Ia ◽  
Post Hoc

<b><i>Background:</i></b> Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Patients can be treated using chlormethine gel, a skin-directed therapy developed and approved for MF. In the randomized, controlled 201 trial, chlormethine gel was found to be noninferior to equal-strength chlormethine ointment. However, there remains a need to gain more insight into outcome measures after treatment. <b><i>Objective:</i></b> The aim of this study was to further investigate the potential of chlormethine gel treatment through a novel post hoc analysis of the 201 trial data (NCT00168064). <b><i>Methods:</i></b> Patients were randomized to chlormethine gel or ointment; response assessments included Composite Assessment of Index Lesion Severity (CAILS) and total body surface area (BSA). In this post hoc analysis, additional subgroup response analyses were performed for stage IA/IB–IIA MF. Very good partial response (75 to &#x3c;100% improvement) was included as an additional response category. Time to response and overall response trends were determined. Finally, multivariate time-to-event analyses were performed to determine whether associations were observed between treatment frequency, response, and adverse events. <b><i>Results:</i></b> Response rates were significantly higher for patients with stage IA MF for CAILS (intent-to-treat [<i>p</i> = 0.0014] and efficacy-evaluable [EE; <i>p</i> = 0.0036] populations) and BSA (EE population [<i>p</i> = 0.0488]) treated with gel versus ointment. Time to first CAILS response and response trends were better for all-stage gel-treated patients overall. No association was seen between treatment frequency and response or occurrence of adverse events at the following visit. An association was observed between the occurrence of contact dermatitis and improved clinical response at the next visit (<i>p</i> = 0.0001). <b><i>Conclusion:</i></b> This post hoc analysis shows that treatment with chlormethine gel may result in higher and faster response rates compared with chlormethine ointment, which confirms and expands results reported in the original analysis. The incidence of contact dermatitis may potentially be a prognostic indicator for clinical response; this needs to be confirmed in a larger population.

scholarly journals Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1284
Author(s):  
Nicolas Delanoy ◽  
Debbie Robbrecht ◽  
Mario Eisenberger ◽  
Oliver Sartor ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Post Hoc Analysis ◽  
Psa Response ◽  
Phase Iii Study ◽  
Psa Progression ◽  
Previously Treated ◽  
Post Hoc

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

Effect of race on the safety and efficacy of pemetrexed (P) therapy in locally advanced and metastatic non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18082-18082
Author(s):  
D. F. Tai ◽  
P. Kulkarni ◽  
Y. Wang ◽  
J. Gill ◽  
C. Obasaju
Keyword(s):  
Clinical Trials ◽  
Cox Model ◽  
Single Agent ◽  
Locally Advanced ◽  
Phase Iii ◽  
Disease Stage ◽  
Safety And Efficacy ◽  
Post Hoc Analysis ◽  
Caucasian Patients ◽  
Post Hoc

18082 Background: P is a multitargeted antifolate active in NSCLC. While a number of clinical trials have evaluated P safety and efficacy in general patient populations, little is known of the possible impact of race on the utility of P therapy in NSCLC. The objective of this post-hoc analysis was to evaluate the effect of race on the safety and efficacy of P (single-agent or in combination) in patients with locally advanced and metastatic NSCLC. Methods: Data from 6 trials with at least 5% non-Caucasian patients were pooled for analyses. One Phase III trial evaluated P in a second-line setting. All other trials used P in Phase II first-line settings. Patients were given at least one dose of P (single-agent or in combination) at 600 mg/m2 (59 patients) or 500 mg/m2 (469 patients) every 21 days. Demographic, safety, and efficacy data were stratified broadly by race, to either Caucasian or non-Caucasian groups. Kaplan-Meier method was used to estimate median survival. The Cox model was used to calculate the hazard ratio (HR) for survival, adjusting for significant prognostic factors, including disease stage, performance status, gender, and line of treatment. Results: Results are summarized in the data table below. The adjusted HR for survival (non-Caucasian versus Caucasian) was 0.89 (p=0.365). Conclusions: In this post-hoc analysis of results from clinical trials using P therapy in NSCLC, race did not have a statistically significant impact on response rate, disease control rate, or survival. However, P therapy appeared to be better tolerated by non-Caucasian patients. [Table: see text] No significant financial relationships to disclose.

scholarly journals Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial

2016 ◽  
Vol 76 (3) ◽  
pp. 534-542 ◽  
Author(s):  
Daniel J Wallace ◽  
Vibeke Strand ◽  
Joan T Merrill ◽  
Serghei Popa ◽  
Alberto J Spindler ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Monoclonal Antibody ◽  
Phase Ii ◽  
Lupus Erythematosus ◽  
Response Rates ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Systemic Lupus ◽  
Post Hoc Analysis ◽  
Post Hoc

ObjectivesThis phase II trial evaluated the efficacy and safety of an interleukin (IL) 6 monoclonal antibody for systemic lupus erythematosus (SLE).MethodsPatients with active disease were randomised to placebo or PF-04236921 10 mg, 50 mg or 200 mg, subcutaneously, every 8 weeks with stable background therapy. SLE Responder Index (SRI-4; primary end point) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) were assessed at week 24. Post hoc analysis identified an enriched population based upon planned univariate analyses.Results183 patients received treatment (placebo, n=45; 10 mg, n=45; 50 mg, n=47; 200 mg, n=46). The 200 mg dose was discontinued due to safety findings and not included in the primary efficacy analysis. The SRI-4 response rates were not significant for any dose compared with placebo; however, the BICLA response rate was significant for 10 mg (p=0.026). The incidence of severe flares was significantly reduced with 10 mg (n=0) and 50 mg (n=2) combined versus placebo (n=8; p<0.01). In patients with greater baseline disease activity (enriched population), the SRI-4 (p=0.004) and BICLA (p=0.012) response rates were significantly different with 10 mg versus placebo. Four deaths (200 mg, n=3; 10 mg, n=1) occurred. The most frequently reported adverse events included headache, nausea and diarrhoea.ConclusionsPF-04236921 was not significantly different from placebo for the primary efficacy end point in patients with SLE. Evidence of an effect with 10 mg was seen in a post hoc analysis. Safety was acceptable for doses up to 50 mg as the 200 mg dose was discontinued due to safety findings.Trial registration numberNCT01405196; Pre-results.

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