Impact of first-line and second-line PFS definitions within a randomized phase III trial in patients (pts) with metastatic pancreatic adenocarcinoma (MPA)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15583-e15583
Author(s):  
L. Dahan ◽  
N. Methy ◽  
J. Seitz ◽  
E. Mitry ◽  
M. Ychou ◽  
...  
Keyword(s):  
Phase Iii ◽  
Time Interval ◽  
Phase Iii Trial ◽  
Kaplan Meier ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Significant Difference ◽  
Opposite Sequence ◽  
Definition Of ◽  
Meaningful Definition

e15583 Background: The FFCD phase III trial in pts with MPA comparing LV5FU2-P followed by gemcitabine (arm A) versus the opposite sequence (arm B) had failed to demonstrate a significant difference in median OS and PFS. The aim of this ancillary study was to investigate definitions of 1st and 2nd line PFS and their impacts on results. Methods: From 08/2003 to 05/2006, 202 pts with measurable MPA, PS 0–2, non prior CT were included in 33 centers, 102 in arm A and 100 in arm B. PFS1 in 1st line was defined as time interval between randomization and progression (P) or death (D) during the 1st line. Alive patients without P have been censored at the beginning of 2nd line or at the last FU. PFS2 in 2nd line was defined as time interval between randomization and P or D during the 2nd line. Alive patients without P during 2nd line have been censored at the last FU. For patients receiving only one line, PFS2 was defined as time interval between randomization and first P or D. Survival curves has been estimated using Kaplan Meier and compared using log-rank Tests. Strict ITT and modified ITT (ie pts receiving 2 lines) analyses were performed Results: Amongst the 202 pts after a median follow-up of 44 months, 69 pts (45 pts due to P) in Arm A and 55 pts (48 pts due to P) in Arm B have received a 2nd line. Median PFS was respectively equal to 3.4 months in Arm A and 3.5 months in Arm B (Stratified Log-Rank p = 0.78). For PFS1 we observed 77 and 93 events respectively in Arm A and B. Median PFS1 was equal to 4.0 months in Arm A and 3.5 months in Arm B (Stratified Log-Rank p = 0.57). For PFS2 we observed 99 and 100 events respectively in Arm A and B. Median PFS2 was equal to 5.0 months in Arm A and 5.8 months in Arm B (Stratified Log-Rank p = 0.68). Restraining PFS2 amongst patients receiving 2 lines (N = 124 pts), we observed 67 and 55 events respectively in Arm A and B, median PFS2 was equal to 6.3 months in Arm A and 8.8 months in Arm B (Stratified Log-Rank p = 0.03) Conclusions: Our results suggest that PFS2 for patients receiving 2 lines was longer when pts received Gemcitabine in 1st line. To be clinically meaningful definition of PFS1 and PFS2 should be optimized regarding censoring rules. New definitions should be proposed and assessed. No significant financial relationships to disclose.

Longitudinal analysis of quality of life (QoL) within a randomized phase III trial in patients (pts) with metastatic pancreatic adenocarcinoma (MPA)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17544-e17544
Author(s):  
F. Bonnetain ◽  
E. Maillard ◽  
J. Seitz ◽  
E. Mitry ◽  
M. Ychou ◽  
...  
Keyword(s):  
Cox Model ◽  
Drop Out ◽  
Phase Iii ◽  
Time Interval ◽  
Phase Iii Trial ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Eortc Qlq C30 ◽  
First Occurrence ◽  
Eortc Qlq

e17544 Background: The FFCD phase III trial in pts with MPA comparing LV5FU2-P followed by gemcitabine (arm A) versus the opposite sequence (arm B) had failed to demonstrate a significant difference in median OS. To longitudinally compare QoL according to treatment sequence we have explore definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut off. Methods: From August 2003 to May 2006, 202 pts with measurable MPA, PS 0–2, non prior CT were included in 33 centers, 102 in arm A and 100 in arm B. QoL was evaluated using EORTC QLQ-C30 every 8 wks up to death. We focused analyses on the following scores: global health (GH), emotional functioning (EF), physical functioning (PF), fatigue (FA), and pain (PA). TUDD were estimated using Kaplan Meier, and compared using log-rank tests. They were defined as the time interval between randomization and the first occurrence of a decrease in QLQ-C30 score ≥ 5 points without any further improvement in QoL score ≥ 5 points or any further available QoL data. These analyses were repeated using a 10 points MCID, and by including deaths as event. Results: Amongst the 202 pts, 179 had completed at least one QoL questionnaire (89%) and the mean number of available QoL data was 3 (SD: 2.14). Using a 5 points MCID as well as 10 points, TUDD of the 5 scores did not differ according to treatment arm. About 25% of patients reported definitive score deteriorations≥ 5 points and 15%≥ 10 points. Including death as event for a 5 points MCID, median TUDD of GH score was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–6.1) in Arm B (log rank p = 0.50). Median TUDD of FA score was 4.8 months (3.5–6.3) in Arm A and 5.6 months (4.2–7.7) in Arm B (log rank p = 0.76). Median TUDD of scores was reached after median PFS and at median time of second-line PFS. While treatment had no impact, multivariate Cox model showed that tumor localization and progression were independently associated with TTDU (p < 0.05). Conclusions: We have investigated QoL analyses modalities using survival techniques dealing with binding drop out missing data and with an easier clinical interpretation of results. Progression seems to negatively impact QoL. No significant financial relationships to disclose.

Treatment of adenocortical carcinoma: 11-year Birmingham experience.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 462-462
Author(s):  
Lenka Zvirinska ◽  
Alice Tew ◽  
Emilio Porfiri
Keyword(s):  
Survival Data ◽  
Standard Treatment ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Limited Efficacy ◽  
Significant Difference ◽  
Unselected Population ◽  
Group 3 ◽  
Time To Relapse

462 Background: Due to the lack of prospective randomized phase III trial data, we have analysed patients with ACC treated between 2000 and 2011. Methods: All the patients given Mitotane (standard treatment of ACC in UHB, Birmingham) where extracted from pharmacy database. Results: 23 patients were identified, age 26-74 (median 53). Follow-up for whole group was 14–167m, median 60. Overall survival (OS) was 3-48m, medium 11.1 patient with slowly growing disease is still alive (167m) with 2nd dg of breast cancer. 19 patients were treated for metastatic disease, 4 in adjuvant setting. 7 patients were managed by endocrinologist only (3 adjuvant, 2 poor PS, 1 reluctant to treatment and 1 details unknown). 16 patients were under shared care. 4 these patients were never exposed to chemotherapy (2 poor PS, 1 returned to Africa, died within 5 months, 1 declined chemotherapy, still alive at 16 months post). 6/19 metastatic patients had chemotherapy as 1st treatment (4 patients etoposide/doxorubicin/cisplatin chemotherapy, 1 etoposide/carboplatin, 1 etoposide/cisplatin), 7 were treated with chemotherapy on PD(6 streptozocin, 1 etoposide/doxorubicin/cisplatin, 1 etoposide/cisplatin). There was no significant difference in OS when those approaches were compared (1st group 7-16 m, median 10, 2nd group 3-14, median 11) But TTP has been slightly worse for treatment on PD as expected (1st group 3-13m, median 6.5; 2nd group 3-14, median 3), although might be due to tendency to use Streptozocin, consistant with preliminary published results of FIRMACT trial.3 patients were treated with 2 lines of chemotherapy (age 30,31, 38), TTP 2- 5 m. Adjuvant patients within our sample has been followed up for limited perion only (11 – 71m, median 22.5), however no recurrence was diagnosed so far.In metastatic patient population 4 patients were treated for recurrence with time to relapse 3-43m, medium 23.5. Conclusions: ACC is heterogenic disease as confirmed by our survival data. In unselected population median OS is comparable to FIRMACT. Consistant with literature review, chemotherapy threatment can be delivered as 1st-line or delayed till PD. 2nd-line chemotherapy is of limited efficacy.

Androgen deprivation therapy (ADT) plus docetaxel (D) versus ADT alone for hormone-naïve metastatic prostate cancer (PCa): Long-term analysis of the GETUG-AFU 15 phase III trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 140-140 ◽  
Author(s):  
Gwenaelle Gravis ◽  
Jean-Marie Boher ◽  
Florence Joly ◽  
Stephane Oudard ◽  
Laurence Albiges ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
High Volume ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Intention To Treat ◽  
Original Analysis ◽  
Definition Of

140 Background: ADT is standard treatment for metastatic PCa. Recently, the E3805 trial reported a survival benefit for (ADT+D) in high volume disease (HVD) patients, whereas the GETUG-15 trial did not demonstrate a survival improvement among a less selected group of patients (pts) with hormone-naïve metastatic PCa. We report an updated analysis of overall survival (OS) of the GETUG 15 trial and aligned the definition of HVD and low volume disease (LVD) subgroups. Methods: Long-termOS was analyzed in the intention-to-treat population (n=385 pts). Additionally, we retrospectively assessed the tumor volume as defined per E3805criteria in all patients enrolled in GETUG 15. Results: See Table. With a median follow-up of 82.9 months (95%CI [80.5-84.3]) (vs 50 months (95%CI [80.5-84.3] in the original analysis), 212 patients (55%) have died. The median OS is 46.5 [39.1-60.6] and 60.9 months [46.1-71.4] in the ADT and in the ADT + D arms, respectively (HR: 0.9 [95%CI: 0.7-1.2]). In HVD patients (n=183, 47.5%), median OS rates were 35.1 months [29.9-44.2] in the ADT alone arm and 39 months [28-52.6] in the ADT+D arm (HR: 0.8 [0.6-1.2]). Conclusions: With longer follow-up, the addition of docetaxel to ADT did not significantly improve OS in patients with hormone-naïve metastatic prostate cancer. In the retrospective analysis using aligned definition of volume of metastasis as E3805, the HVD outcomes were similar to E3805 for ADT alone and there was a non-significant 4 months increase in OS with ADT+D, in this underpowered subset. Clinical trial information: 00104715. [Table: see text]

The combination of capecitabine (C), irinotecan (I) and oxaliplatin (O) (XELOXIRI) as first line treatment of metastatic colorectal cancer (MCRC): Preliminary results of a pilot study by the Gruppo Oncologico Nord-Ovest (G.O.N.O.)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4096-4096 ◽  
Author(s):  
G. Masi ◽  
S. Bursi ◽  
F. Loupakis ◽  
M. Barletta ◽  
G. Baldi ◽  
...  
Keyword(s):  
Pilot Study ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Recommended Dose ◽  
First Line ◽  
Phase Iii Trial ◽  
Preliminary Results ◽  
Plasma Pharmacokinetics ◽  
Definition Of

4096 Background: FOLFOXIRI demonstrated manageable toxicities and improved activity and efficacy compared to FOLFIRI in MCRC in a phase III trial by the G.O.N.O. group. Oral C has demonstrated similar efficacy to 5-FU and might substitute 5-FU in the FOLFOXIRI regimen. Methods: The G.O.N.O. started a pilot study to evaluate the combination of escalating doses of C with fixed doses of I, O (XELOXIRI) in metastatic and not resectable CRC patients (pts). The objectives of the study are the definition of the recommended dose (RD) of C in combination with I and O, safety and activity of the combination and analysis of plasma pharmacokinetics. The planned treatment in the first 3 patients was: I 165 mg/sqm over 1-h on day 1, O 85 mg/sqm over 2-h on day 1 and C 2,500 mg/sqm/die from day 1 to 7, repeated every 2 weeks. C dose was increased to 3,000 mg/sqm/die or decreased to 2,000 mg/sqm/die in subsequent groups of 3 to 6 pts on the basis of the observed dose limiting toxicities (DLT). Results: Up today 33 patients have been enrolled. Main patients characteristic are: sex (M/F) = 22/11, PS (0/1/2) = 28/4/1, age (median/range) = 65/42–76, sites of disease (single/multiple) = 18/15. The DLT was G3–4 diarrhea that was observed in 2 out 6 patients receiving C at 2500 mg/sqm, in 2 out 3 patients receiving C at 3,000 mg/sqm and in 1 out 6 patients receiving C at 2,000 mg/sqm. This last dose was defined the RD. Among the 23 patients treated at the RD main G3–4 toxicities were: diarrhea 17%, neutropenia 26%, thrombocytopenia 9%, neurotoxicity 4%. One toxic death for diarrhea and sepsis occurred. Up today 21 out of the 23 patients (2 patients too early) treated at the RD are assessable for response (ITT analysis) and 15 RP, 3 SD and 3 treatment failures have been observed with a response rate of 71% (95% CI: 48–89%). At a median follow-up of 10.3 months median PFS is 9.0+ months and median OS isn’t yet reached. Conclusions: XELOXIRI is a feasible regimen with diarrhea being the DLT. The recommended dose of C is 2,000 mg/sqm. At the RD toxicity is manageable and preliminary results in terms of activity are promising. Partially supported by Fondazione ARCO. No significant financial relationships to disclose.

ACCORD12/0405-Prodige 2 phase III trial neoadjuvant treatment in rectal cancer: Results after 5 years of follow-up.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 490-490 ◽  
Author(s):  
Eric Francois ◽  
Sophie Gourgou-Bourgade ◽  
David Azria ◽  
Thierry Conroy ◽  
Olivier Bouche ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Clin Oncol ◽  
Cumulative Incidence ◽  
Neoadjuvant Treatment ◽  
Bowel Function ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Significant Difference

490 Background: The ACCORD 12 randomized trial was aiming at improving ypCR by increasing the radiation dose and adding oxaliplatin (OX) to a standard RT 45 Gy with concurrent capecitabine. On short term benefit of OX was not demonstrated (Gérard JP et al. J Clin Oncol. 2010;28:1638-44) at 3 years no significant difference in clinical outcome was achieved (Gérard JP et al. J Clin Oncol. 2012;30:4558-65. François E et al. Radiother Oncol. 2014;110:144-9). This is an update of results at 5 years. Methods: Between 11/2005 and 07/2008, 598 patients were randomized. Inclusion criteria: adenocarcinoma of rectum accessible to digital examination, T3 Nx M0 (or T2 distal anterior rectum). Randomization was between two neoadjuvant treatments chemo radiotherapy: Cap45 (45 Gy + capecitabine) and Capox50 (50 Gy + cape. and oxaliplatin). Main end point was sterilization of the operative specimen. Bowel function for patients treated with anterior resection was analyzed with a global score (1 very poor to 7 excellent). A total of 253 patients received adjuvant chemotherapy usually with FOLFOX: 133 in Cap45, 120 in Capox50. Results: In the ITT population, with a median follow-up of 60 months, updated carcinologic results were calculated using the Kaplan-Meier method. Out of 299 pts randomized in CAP45 and 299 pts in CAPOX50 results were respectively the following 1) 5y-cumulative incidence of Loc. Recurrence : 8.8% vs 7.8% (p = 0.78 HR = 0.92 [0.51-1.66]) 2) 5y-cumulative incidence of dist metastasis : 29.3% vs 27.1% (p = 0.48 HR = 0.89 [0.62-1.54]) 3) 5y-disease free survival rate : 60.4% vs 64.7% (p = 0.25 HR = 0.86 [0.66-1.11]) 4) 5y-overall survival rate : 76.4% vs 81.9% (p = 0.06 HR = 0.71 [0.50-1.01]) 5) bowel function median score : 5.2 [1-7] vs 4.9 [1-7]. Conclusions: At 5 years there was no significant difference in terms of local recurrence or distant metastases rates between both regimens. The new finding is a trend for improved overall survival in the Capox 50 groups may be related to subsequent salvage secondary treatments. At time of meeting the prognostic factors will be available in details and these results put in perspective with other phase III trial testing the role of oxaliplatin in Europe and the US. Clinical trial information: NCT00227747.

CTONG1104: Adjuvant gefitinib versus chemotherapy for resected N1-N2 NSCLC with EGFR mutation—Final overall survival analysis of the randomized phase III trial 1 analysis of the randomized phase III trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9005-9005 ◽  
Author(s):  
Yi-Long Wu ◽  
Wenzhao Zhong ◽  
Qun Wang ◽  
Weimin Mao ◽  
Song-Tao Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Target Therapy ◽  
Disease Free Survival ◽  
Subsequent Treatment ◽  
Stage Ii ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Significant Difference

9005 Background: ADJUVANT-CTONG1104, a randomized phase 3 trial showed adjuvant gefitinib treatment significantly improved disease-free survival (DFS) vs standard doublet chemotherapy in patients (pts) with epidermal growth factor receptor ( EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). 5-year survival rate of N1N2 were 38%-50% in IASLC staging system. Here, we present the final overall survival (OS) results from the study. Methods: From Sep 2011 to April 2014, 222 patients, aged 18-75 years, with EGFR activating mutation through completely resection and diagnosed as stage II-IIIA (N1-N2) NSCLC pathologically from 27 sites were enrolled. The enrolled patients were 1:1 randomized to receive adjuvant gefitinib (250 mg once per day) for 24 months (G, n=111) or vinorelbine (25 mg/m2, d1 and d8) plus cisplatin (75 mg/m2, d1) every 3 weeks for 4 cycles (C, n=111). The primary endpoint was DFS in the ITT population. Secondary endpoints included OS, 3 and 5-year DFS rate, 5-year OS rate. The subsequent therapy data were collected, including crossover from C to G, re-challenge TKI and other treatment. Data cut-off date was Jan. 13, 2020. Results: A median follow-up was 76.9 months. The median OS (mOS) was 75.5 months based on 95 (42.8%) events in ITT whole population. The mOS was 75.5m in G arm and 79.2m in C arm (HR 0.96, 95%CI 0.64-1.43, p=0.823). The 3, 5-year OS rate were 68.6%, 53.8% in G and 67.5%, 52.4% in C respectively. DFS in 3, 5-y were 40.3%, 23.4% in G and 33.2%, 23.7% in C, respectively (P3-y=0.395, P5-y=891). All predefined subgroups including age, gender, lymph node, EGFR mutation type had no significant difference in statistics but in favor of G arm in trend. Subsequent treatment especially targeted therapy contributed most to OS (HR = 0.46, 95% CI 0.26 – 0.83). Median OS of patients receiving subsequent target therapy was75.5m (n=35), 36.4m in other treatment (n=33; (P<0.001). For G mOS were 75.5 (n=15; target therapy) and 35.0 (n=18; other, p<0.001), for C 62.8m (n=20) and 46.8m (n=15; p=0.251). The RR was 26.7%, DCR 66.7%, mPFS 14.1m and mOS 19.6m for patients with rechallenged EGFR TKI in G arm (n=15). No novel unexpected SAE was observed during follow up. Conclusion The DFS survival advantage did not translate to OS difference in ADJUVANT trial. The OS with 75.5m was the best one of survival in completely resected N1N2 NSCLC comparing with historical data and sequent TKI treatment contribute to overall survival. Clinical trial information: NCT01405079.

scholarly journals Identification of characteristics, risk factors, and predictors of recurrent LVAD thrombosis: conditions in HeartWare devices

2020 ◽  
Author(s):  
Takayuki Gyoten ◽  
Michiel Morshuis ◽  
Sebastian V. Rojas ◽  
Marcus-André Deutsch ◽  
René Schramm ◽  
...  
Keyword(s):  
Cox Regression ◽  
Left Ventricular ◽  
Rank Test ◽  
Time Interval ◽  
Recurrent Thrombosis ◽  
Ventricular Assist ◽  
Long Term Study ◽  
Kaplan Meier ◽  
Significant Difference

Abstract Background Redictors of repetitive left-ventricular assist device (LVAD)-thrombosis have not been studied yet. Methods We identified predictors of recurrent LVAD thrombosis in HeartWare (HVAD) patients in a long-term study from 2010 until 2020. We included all patients with two or more thrombolysis treatments for repetitive HVAD thrombosis and effectiveness of thrombolytic therapy was defined as freedom from stroke, death, another HVAD thrombosis, or surgical device exchange within 30 days after the event. Study endpoints also include all-cause mortality and heart transplantation. Results A total of 534 HVAD implantations have been screened, and 73 patients (13.7%) developed first HVAD thrombosis after a median of 10 months (IQR; 6–21 months). 46 of these patients had effective thrombolysis in 71.7% (n = 33/46). After a median of 14 months (IQR 4–32 months) follow-up, 17 patients (51.5%) had developed a second HVAD thrombosis and all were treated with t-PA therapy again, resulting in effectiveness in 76.5% (n = 13/17). The four patients with ineffective t-PA therapy underwent subsequent surgical HVAD exchange. Multiple Cox regression model analysis revealed time interval between HVAD implantation and first thrombosis as an independent risk factor of recurrent thrombosis (HR, 0.93, 95% CI 0.87–0.99, p = 0.031). Kaplan–Meier analysis at 3 year follow-up showed no significant difference in overall survival for recurrent vs non-recurrent thrombosis groups (log-rank test, p = 0.959). Conclusion Recurrent HVAD thrombosis mostly appears within 12 months after first thrombosis. Systemic t-PA therapy for recurrent pump thrombosis seems safe, achieving comparable effectiveness rates to initial t-PA therapy. Survival does not differ between patients with or without recurrent HVAD thrombosis.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

Percutaneous hepatic perfusion (PHP) with melphalan for patients with ocular melanoma liver metastases: Preliminary results of FOCUS (PHP-OCM-301/301A) phase III trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9510-9510
Author(s):  
Jonathan S. Zager ◽  
Marlana Orloff ◽  
Pier Francesco Ferrucci ◽  
Evan Scott Glazer ◽  
Aslam Ejaz ◽  
...  
Keyword(s):  
Hepatic Metastases ◽  
Ideal Body Weight ◽  
Standard Of Care ◽  
Ocular Melanoma ◽  
Phase Iii ◽  
Point Estimate ◽  
Phase Iii Trial ◽  
Kaplan Meier ◽  
Independent Review ◽  
Phase Iii Study

9510 Background: Ocular melanoma, the most common intraocular malignancy, frequently metastasizes to the liver but to date there is no established standard of care for hepatic-dominant ocular melanoma patients. The FOCUS trial began as a randomized, phase III trial (301) comparing PHP with best alternative care (BAC). The trial was subsequently amended (301A) to remove the BAC arm due to enrollment concerns. Methods: Eligible patients with hepatic-dominant ocular melanoma were randomized 1:1 to receive PHP or BAC (investigator’s choice of TACE, pembrolizumab, ipilimumab, or dacarbazine) on the 301 trial. All eligible patients received PHP on the 301A trial. PHP patients could receive up to 6 PHP treatments, repeated every 6-8 weeks with melphalan dosed at 3.0mg/kg ideal body weight (IBW). Patients with progressive disease (PD) were discontinued from study treatment and all patients are followed until death. Patientswere imaged every 12 (±2) weeks until PD. The primary endpoint, ORR (per RECIST 1.1) as assessed by Independent Review Committee, will be characterized by the point estimate and 95% CI for each group (PHP and BAC). Categorical efficacy variables will be presented as frequency counts and percentages and 95% CI. Time-to-event variables will be summarized using Kaplan-Meier methods (median and 95% CI). Results: 144 patients were enrolled overall; 102 were assigned to PHP (301: n=43; 301A: n=59) and 42 were assigned to BAC. 91 PHP patients received treatment (301: n=40; 301A: n=51) and 32 BAC patients received treatment. At the time of this analysis, 4 PHP patients were still ongoing on study treatment with a minimum follow-up of 24 weeks. 79 PHP-treated patients and 29 BAC-treated patients were evaluable for response. ORR among PHP patients was 32.9% (26/79; 95% CI: 22.75-40.40%). ORR among BAC patients was 13.8% (4/29; 95% CI: 3.89-31.66%). The median PFS was 9.03 months (95% CI: 6.24-11.83) among PHP patients and was 3.06 months (95% CI: 2.69-5.65) among BAC patients; this difference was statistically significant ( p=0.0004). Among the 94 patients assessed for safety after treatment with PHP, 40.4% of patients experienced a serious treatment-emergent adverse event, the majority of which were hematological and resolved without sequelae. There were no treatment related deaths in the trial. Conclusions: In this analysis of preliminary data from the FOCUS trial, PHP demonstrates a statistically superior ORR and significantly prolonged PFS in comparison with BAC in the treatment of hepatic metastases from ocular melanoma. The data is encouraging as efficacious treatments for hepatic metastases from ocular melanoma are desperately needed. These early data show an improvement over the previous phase III study in terms of both efficacy (ORR and PFS) as well as toxicity using second generation filters. Clinical trial information: NCT02678572.

Sign in / Sign up

Export Citation Format

Share Document