scholarly journals Rucaparib maintenance treatment for recurrent ovarian carcinoma: the effects of progression-free interval and prior therapies on efficacy and safety in the randomized phase III trial ARIEL3

2021 ◽  
pp. ijgc-2020-002240
Author(s):  
Andrew R Clamp ◽  
Domenica Lorusso ◽  
Amit M Oza ◽  
Carol Aghajanian ◽  
Ana Oaknin ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Free Interval ◽  
Intent To Treat ◽  
Treat Population

IntroductionIn ARIEL3 (NCT01968213), the poly(adenosine diphosphate-ribose) polymerase inhibitor rucaparib significantly improved progression-free survival versus placebo regardless of biomarker status when used as maintenance treatment for recurrent ovarian cancer. The aim of the current analyses was to evaluate the efficacy and safety of rucaparib in subgroups based on progression-free interval following penultimate platinum, number of prior chemotherapies, and prior use of bevacizumab.MethodsPatients were randomized 2:1 to rucaparib 600 mg twice daily or placebo. Within subgroups, progression-free survival was assessed in prespecified, nested cohorts: BRCA-mutant, homologous recombination deficient (BRCA-mutant or wild-type BRCA/high genomic loss of heterozygosity), and the intent-to-treat population.ResultsIn the intent-to-treat population, median investigator-assessed progression-free survival was 8.2 months with rucaparib versus 4.1 months with placebo (n=151 vs n=76; HR 0.33, 95% CI 0.24 to 0.46, p<0.0001) for patients with progression-free interval 6 to ≤12 months, and 13.6 versus 5.6 months (n=224 vs n=113; HR 0.39, 95% CI 0.30 to 0.52, p<0.0001) for those with progression-free interval >12 months. Median progression-free survival was 10.4 versus 5.4 months (n=231 vs n=124; HR 0.42, 95% CI 0.32 to 0.54, p<0.0001) for patients who had received two prior chemotherapies, and 11.1 versus 5.3 months (n=144 vs n=65; HR 0.28, 95% CI 0.19 to 0.41, p<0.0001) for those who had received ≥3 prior chemotherapies. Median progression-free survival was 10.3 versus 5.4 months (n=83 vs n=43; HR 0.42, 95% CI 0.26 to 0.68, p=0.0004) for patients who had received prior bevacizumab, and 10.9 versus 5.4 months (n=292 vs n=146; HR 0.35, 95% CI 0.28 to 0.45, p<0.0001) for those who had not. Across subgroups, median progression-free survival was also significantly longer with rucaparib versus placebo in the BRCA-mutant and homologous recombination deficient cohorts. Safety was consistent across subgroups.ConclusionsRucaparib maintenance treatment significantly improved progression-free survival versus placebo irrespective of progression-free interval following penultimate platinum, number of lines of prior chemotherapy, and previous use of bevacizumab.

Re-irradiation in head and neck cancers: an Indian tertiary cancer centre experience

2014 ◽  
Vol 128 (11) ◽  
pp. 996-1002 ◽  
Author(s):  
S Mallick ◽  
A K Gandhi ◽  
N P Joshi ◽  
S Pandit ◽  
S Bhasker ◽  
...  
Keyword(s):  
Head And Neck ◽  
Recurrent Disease ◽  
Progression Free Survival ◽  
Second Primary ◽  
Disease Free Interval ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Free Interval ◽  
Second Primaries ◽  
Disease Free

AbstractObjective:To explore the treatment outcomes of patients treated with re-irradiation for recurrent or second primary head and neck cancer.Method:An analysis was performed of 79 head and neck cancer patients who underwent re-irradiation for second primaries or recurrent disease from January 1999 to December 2011.Results:Median time from previous radiation to re-irradiation for second primary or recurrence was 53.6 months (range, 2.7–454.7 months). Median age at diagnosis of first primary was 54 years. Median re-irradiation dose was 45 Gy (range, 45–60 Gy). Acute grade 3 or worse toxicity was seen in 30 per cent of patients. Median progression-free survival for recurrent disease was 15.0 months (95 per cent confidence interval, 8.33–21.66). The following factors had a statistically significant, positive impact on progression-free survival: patient age of less than 50 years (median progression-free survival was 29.43, vs 13.9 months for those aged 50 years or older; p = 0.004) and disease-free interval of 2 years or more (median progression-free survival was 51.66, vs 13.9 months for those with less than 2 years disease-free interval).Conclusion:Re-irradiation of second primaries or recurrences of head and neck cancers with moderate radiation doses yields acceptable progression-free survival and morbidity rates.

Phase III Study of Denileukin Diftitox (ONTAK®) To Evaluate Efficacy and Safety in CD25+ and CD25- Cutaneous T-Cell Lymphoma (CTCL) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 696-696 ◽  
Author(s):  
Andres Negro-Vilar ◽  
Zofia Dziewanowska ◽  
Eric Groves ◽  
Elyane Lombardy ◽  
Victor Stevens
Keyword(s):  
Adverse Events ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Denileukin Diftitox ◽  
Duration Of Response ◽  
Phase Iii Study

Abstract Denileukin diftitox (ONTAK®) is a genetically engineered fusion protein composed of the enzymatically active domain of diphtheria toxin and the full length sequence of interleukin-2 (IL-2), designed to target malignancies expressing the IL-2 receptor. The drug is approved for the treatment of CTCL in patients expressing the CD-25 component of the IL-2 receptor. L4389-14 is a phase III study designed to further evaluate the efficacy and safety of denileukin diftitox (DD) in distinct subgroups of CTCL patients. The study met its accrual goal of 90 patients and included three subgroups of patients: 1) CD25 (+) patients that crossover from a placebo course of treatment in a companion study (L4389-11) and had progressed or failed to respond during an 8-course placebo treatment (N=34); 2) CD25 (−) patients (N=36) and 3) CD25 (+) patients that had previously been treated with DD, responded, and subsequently relapsed (retreatment group, N=22). Patients entered the study at stages Ia to III and received DD at a dose schedule of 18mcg/Kg/day by IV infusion once daily for 5 days every 3 weeks for up to 8 cycles. Efficacy of treatment was assessed based on tumor burden, lymph nodes, lymphocyte count, and patient status (PGA) at every cycle, beginning on cycle 2. A response assessment required confirmation in two subsequent cycles. Responses were evaluated by an independent Drug Evaluation Review Committee. Assessment of activity of DD across the 3 groups based on an analysis of the data is shown in the table below. Patient demographics were consistent across subgroups and representative of a general CTCL population. Disease status at baseline was Stage IIa or earlier 66% of patients and stage IIb or higher 34% of patients. About 46% of patients presented with mild to severe erythroderma. Adverse events were similar to those previously observed with ONTAK. Serious adverse events of ≥5% incidence were nausea (9%), vomiting (5%), capillary leak syndrome (5%), pyrexia (9%) and infections (10%). The results of this large phase III trial showed very consistent efficacy of denileukin diftitox across treatment-naïve CD25 (+) and CD25 (−) patients, as well as in patients undergoing retreatment with DD. Duration of response and progression free survival were also quite favorable across the different CTCL subgroups. Response Assessment CD25 (+) Placebo Crossover CD25 (−) CD25 (+) Retreatment N = 34 36 22 ORR (CR/CCR/PR) 47.1% 30.6% 36.4% CR/CCR 17.6% 8.3% 9.1% PR 29.4% 22.2% 27.3% SD 29.4% 44.4% 31.8% PD 20.6% 25.0% 31.8% Duration of Response (days) 820 340 274 Progression Free Survival (days) 870 Not reached 429

Biweekly Gemcitabine-Oxaliplatin and Dexamethasone for Relapsed/Refractory Malignant Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4952-4952
Author(s):  
Hawk Kim ◽  
Je-Hwan Lee ◽  
Young Don Joo ◽  
Sung Hwa Bae ◽  
Jung-Hee Lee ◽  
...  
Keyword(s):  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Drop Out ◽  
First Line ◽  
Free Survival ◽  
Prior Chemotherapy ◽  
Median Progression Free Survival ◽  
Dose Dense ◽  
Intent To Treat

Abstract Abstract 4952 Gemcitabine (GEM) and oxaliplatin (OX) are commonly used as weekly or biweekly therapy. In this regard, dose dense biweekly schedule seems of reasonable investigational value in GEM and OX combination for non-Hodgkin lymphoma (NHL). We conducted phase II study to evaluate the efficacy of the combination chemotherapy consisting of GEM, OX and dexamethasone (GemDOx) as a biweekly regimen in patients with relapsed or refractory NHL. Primary end point was objective response rate and secondary end points were toxicities, progression-free survival, overall survival, ASCC efficacy, rate for proceeding to ASCT. The inclusion criteria were relapsed or refractory malignant aggressive NHL of any histological subtypes: Patients who have refractory to first-line CHOP-like regimen; Patients who have first relapsed after first-line CHOP-like regimen or upfront autologous or allogeneic hematopoietic stem cell transplantation Chemotherapy was repeated every 4 weeks. Gemcitabine 1000 mg/m2 in NS 500 mL was administered IV as a fixed dose rate infusion (FDRI, 10 mg/m2/min) on days 1 and 15. OX 85 mg/m2/d in 5DW 500 mL was administered IV over 6 hour on day 1 and 15. Dexamethasone 40 mg was admistered orally on day 1 through 4. All 29 patients were enrolled in this phase II study. Patients were male in 18 (62.1%), DLBCL in 16 (55.2%), stage III/IV in 25 (79.3%) and relapsed NHL in 23 (79.3) patients. Five (17.2%) patients had relapsed after upfront autologous/allogeneic stem cell transplantation. The most common prior chemotherapy was R-CHOP (n=16, 55.2%) and 17 (58.6%) were exposed to rituximab as prior chemotherapy. The median age and median prior chemotherapy were 53 (range 26–74) years old and 1 (range 1–4) cycle, respectively. IPI at relapse were 3/4 in 11 (37.9%). Only 17 (58.6%) and 9 (31.0%) patients could finish 2 or more and 4 or more cycles, respectively, and median received cycle was 2 (range 0.5–8). Four patients completed planned all 6 or more cycles, and 4 patients stopped GemDOx after 4 cycles for ASCT, and 1 patient lost initial response and progressed after 4 cycles. The reasons of drop-out were progressed disease in 15 (51.7%), lost to follow-up in 4 (13.8%), discrete of attending physician in 1 (3.4%) and withdraw of consent in 1 (3.4%). Maximal response rate was 27.9% (CR in 13.8%; PR in 13.8%) in intent-to-treat basis and 47.0% (CR in 23.5% and PR in 23.5%) among patients who had received at least 2 cycles of GemDOx. Stable disease was observed in 6 (20.7%) in intent-to-treat basis and 5 (29.4%) among patients who had received at least 2 cycles of GemDOx. Among patients who received 2 or more cycles, ORR was 53.4% (CR in 26.7% and PR in 26.7%) in relapsed NHL and 0% (SD in 50% and PD in 50%) in refractory NHL. Median survival and median progression-free survival were 20.526 (95% CI, 8.945–32.108) and 3.947 (95% CI, 0–10.358), respectively in all patients (Figure 1). Among patients who had completed 2 or more cycles, median survival and median progression-free survival were not reached and 10.625 (95% CI, 0–21.575), respectively. In conclusion, dose-dense biweekly GemDOx showed activity against highly unfavorable relapsed NHL, but failed to show superior overall response rate especially against refractory NHL. The main cause of failure was progressive disease although considering high drop-out rate. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efficacy and safety of lenvatinib in an elderly patient with metastatic papillary thyroid carcinoma and cardiological comorbidity: a case report

2019 ◽  
Vol 15 (24s) ◽  
pp. 27-33 ◽  
Author(s):  
Agnese Latorre ◽  
Agnese Maria Fioretti ◽  
Francesco Giotta ◽  
Vito Lorusso
Keyword(s):  
Atrial Fibrillation ◽  
Thyroid Carcinoma ◽  
Progression Free Survival ◽  
Chronic Atrial Fibrillation ◽  
Differentiated Thyroid Carcinoma ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Select Trial

Lenvatinib significantly prolonged progression-free survival versus placebo in patients with radio-iodine refractory differentiated thyroid carcinoma. However, the primary adverse effects of any grade that occurred in >40% of patients in the lenvatinib group of the Phase III SELECT trial was hypertension (67.8%). Therefore, this drug should be used with caution in patients with cardiological morbidity. Here, we describe the case of a 73-year-old man with hypertension, obesity and chronic atrial fibrillation, who received lenvatinib for 6 months in the absence of cardiological symptoms.

scholarly journals Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group

2008 ◽  
Vol 26 (35) ◽  
pp. 5748-5754 ◽  
Author(s):  
Michael B. Atkins ◽  
Jessie Hsu ◽  
Sandra Lee ◽  
Gary I. Cohen ◽  
Lawrence E. Flaherty ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Response Rates ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Median Progression Free Survival

Purpose Phase II trials with biochemotherapy (BCT) have shown encouraging response rates in metastatic melanoma, and meta-analyses and one phase III trial have suggested a survival benefit. In an effort to determine the relative efficacy of BCT compared with chemotherapy alone, a phase III trial was performed within the United States Intergroup. Patients and Methods Patients were randomly assigned to receive cisplatin, vinblastine, and dacarbazine (CVD) either alone or concurrent with interleukin-2 and interferon alfa-2b (BCT). Treatment cycles were repeated at 21-day intervals for a maximum of four cycles. Tumor response was assessed after cycles 2 and 4, then every 3 months. Results Four hundred fifteen patients were enrolled, and 395 patients (CVD, n = 195; BCT, n = 200) were deemed eligible and assessable. The two study arms were well balanced for stratification factors and other prognostic factors. Response rate was 19.5% for BCT and 13.8% for CVD (P = .140). Median progression-free survival was significantly longer for BCT than for CVD (4.8 v 2.9 months; P = .015), although this did not translate into an advantage in either median overall survival (9.0 v 8.7 months) or the percentage of patients alive at 1 year (41% v 36.9%). More patients experienced grade 3 or worse toxic events with BCT than CVD (95% v 73%; P = .001). Conclusion Although BCT produced slightly higher response rates and longer median progression-free survival than CVD alone, this was not associated with either improved overall survival or durable responses. Considering the extra toxicity and complexity, this concurrent BCT regimen cannot be recommended for patients with metastatic melanoma.

scholarly journals Anti-angiogenic Therapy for Advanced Primary Pulmonary Lymphoepithelioma-like Carcinoma: a Retrospective Multicenter Study

2021 ◽  
Author(s):  
Hejing Bao ◽  
LingZhen Ma ◽  
Mengge Yu ◽  
Xiaoli Lin ◽  
Chengzhu Zhao ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Research Data ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Median Progression Free Survival ◽  
Retrospective Multicenter Study ◽  
Better Than

Abstract Purpose: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC). Currently, there is still lack of research data on anti-angiogenic therapy of advanced PPLELC. The purpose of this study was to investigate the efficacy and safety of anti-angiogenic therapy combined with chemotherapy compared with traditional chemotherapy for these patients.Methods: Advanced PPLELC patients admitted to six grade A hospitals from January 2013 to January 2021 were selected. The patients received anti-angiogenic therapy combined with chemotherapy(AT group) or chemotherapy (CT group)alone.Results: A total of 65 patients were enrolled in this study, including 31 patients in the AT group treated with anti-angiogenic therapy combined with chemotherapy, and 34 patients in the CT group treated with chemotherapy alone. As of October 1, 2021, the median progression-free survival in the AT group was 11.2 months [95% confidence interval (CI), 5.9-16.5], The median progression-free survival in the CT group was 7.0 months [95%CI, 5.1-8.9][Hazard Ratio (HR), 0.49; 95%CI, 0.29-0.83; P=0.008]. The 1-year PFS rates were 41.9% and 17.6%, respectively. The ORR of two groups were 45.2% (95% CI, 0.27 to 0.64), 38.2% (95% CI, 0.21 to 0.56), (P = 0.571). The DCR of two groups were 93.5% (95% CI, 0.84 to 1.03), 88.2% (95% CI, 0.77 to 1.00), (P = 0.756).Conclusions: Among patients with advanced PPLELC, the progression free survival of patients with anti-angiogenic therapy combined with chemotherapy is better than that of patients with chemotherapy alone. Anti-angiogenic therapy combined with chemotherapy is an optional treatment scheme.

scholarly journals Efficacy and Safety of Bevacizumab Plus Erlotinib in Patients with Renal Medullary Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2170
Author(s):  
Andrew J. Wiele ◽  
Devaki Shilpa Surasi ◽  
Priya Rao ◽  
Kanishka Sircar ◽  
Xiaoping Su ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Medullary Carcinoma ◽  
Tumor Burden ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Renal Medullary Carcinoma ◽  
Grade 3

Purpose: To assess the efficacy and safety of bevacizumab plus erlotinib in patients with RMC. Methods: We retrospectively reviewed the records of patients with RMC treated with bevacizumab plus erlotinib at our institution. Results: Ten patients were included in the study. Two patients achieved a partial response (20%) and seven patients achieved stable disease (70%). Tumor burden was reduced in seven patients (70%) in total, and in three out of five patients (60%) that had received three or more prior therapies. The median progression-free survival (PFS) was 3.5 months (95% CI, 1.8–5.2). The median overall survival (OS) from bevacizumab plus erlotinib initiation was 7.3 months (95% CI, 0.73–13.8) and the median OS from diagnosis was 20.8 months (95% CI, 14.7–26.8). Bevacizumab plus erlotinib was well tolerated with no grade ≥4 adverse events and one grade 3 skin rash. Dose reduction was required in one patient (10%). Conclusions: Bevacizumab plus erlotinib is clinically active and well tolerated in heavily pre-treated patients with RMC and should be considered a viable salvage strategy for this lethal disease.

scholarly journals ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA–MONO) and rucaparib in combination with nivolumab (ATHENA–COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer

2021 ◽  
pp. ijgc-2021-002933
Author(s):  
Bradley J Monk ◽  
Robert L Coleman ◽  
Keiichi Fujiwara ◽  
Michelle K Wilson ◽  
Amit M Oza ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Standard Treatment ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Platinum Based Chemotherapy

BackgroundThe optimal treatment strategy for women with newly diagnosed ovarian cancer has yet to be determined. Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated substantial improvement in progression-free survival as monotherapy maintenance treatment in the frontline setting versus active surveillance. Furthermore, preclinical and early clinical studies have shown that PARP inhibitors and immune checkpoint inhibitors have synergistic antitumor activity and may provide an additional therapeutic option for patients in this population.Primary ObjectivesIn women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer, we wish to assess the efficacy of frontline maintenance treatment with the PARP inhibitor rucaparib versus placebo following response to platinum-based chemotherapy (ATHENA–MONO), and to assess the combination of rucaparib plus nivolumab (a programmed death receptor 1 (PD-1)–blocking monoclonal antibody) versus rucaparib alone (ATHENA–COMBO).Study Hypothesis(1) Maintenance therapy with rucaparib monotherapy may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting. (2) The combination of nivolumab plus rucaparib may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting compared with rucaparib alone.Trial DesignATHENA is an international, randomized, double-blind, phase III trial consisting of two independent comparisons (ATHENA–MONO and ATHENA–COMBO) in patients with newly diagnosed platinum-sensitive ovarian cancer. Patients are randomized 4:4:1:1 to the following: oral rucaparib+ intravenous nivolumab (arm A); oral rucaparib + intravenous placebo (arm B); oral placebo+ intravenous nivolumab (arm C); and oral placebo + intravenous placebo (arm D). The starting dose of rucaparib is 600 mg orally twice a day and nivolumab 480 mg intravenously every 4 weeks. ATHENA–MONO compares arm B with arm D to evaluate rucaparib monotherapy versus placebo, and ATHENA–COMBO evaluates arm A versus arm B to investigate the effects of rucaparib and nivolumab in combination versus rucaparib monotherapy. ATHENA–MONO and ATHENA–COMBO share a common treatment arm (arm B) but each comparison is independently powered.Major Inclusion/Exclusion CriteriaPatients ≥18 years of age with newly diagnosed advanced, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer who have achieved a response after completion of cytoreductive surgery and initial platinum-based chemotherapy are enrolled. No other prior treatment for ovarian cancer, other than the frontline platinum regimen, is permitted.Primary EndpointThe primary endpoint is investigator-assessed progression-free survival by Response Evaluation Criteria in Solid Tumors v1.1.Sample SizeApproximately 1000 patients have been enrolled and randomized.Estimated Dates for Completing Accrual and Presenting ResultsThe trial completed accrual in 2020. While dependent on event rates, primary results of ATHENA–MONO are anticipated in early 2022 and results of ATHENA–COMBO are anticipated to mature at a later date.Trial RegistrationThis trial is registered at clinicaltrials.gov (NCT03522246).

scholarly journals Bortezomib, Lenalidomide and Low-Dose Dexamethasone (VRD) Versus Lenalidomide and Low-Dose Dexamethasone (Ld) for Newly-Diagnosed Multiple Myeloma- a Randomized Phase III Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 906-906
Author(s):  
Anjali Mookerjee ◽  
Ritu Gupta ◽  
Shivali Jasrotia ◽  
Ranjit Sahoo ◽  
Rakesh Kumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Low Dose ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Grade 3

Abstract Background: In this prospective study, we compared VRD with Ld as induction therapy for newly-diagnosed Multiple myeloma patients. The primary objective of this study is to compare the progression-free survival in the 2 arms. Methods: Between September 2014 and Oct 2016, 144 patients have been recruited and randomly assigned to receive 4 cycles of either Bortezomib 1.3 mg/m2 SC on days 1, 8, 15 and 22 with Lenalidomide 15mg/day from day 1 to 14 (Arm A) or Lenalidomide 25 mg/day from day 1 to 21 (Arm B). Patients in both arms received oral dexamethasone 40 mg on days 1,8,15 and 22. Both treatment regimens were 28-day cycles. All patients received 75 mg aspirin daily, acyclovir prophylaxis and monthly zoledronic acid. Response assessment was done at the end of the 4th cycle using the International Myeloma Working Group (IMWG) uniform response criteria. The study was approved by the Institute Ethics Committee (Ref IEC/NP-264/01-08-2014, RP-7/2014). Results: These are the results from an analysis of 143 patients (arm A-74, arm B-69). Baseline characteristics of patients were similar in both arms with respect to age, gender, ISS and DS stage, immunoglobulin subtype and serum LDH. Patients' median age is 56 years (range 31-70) in arm A and 52 years (range 28-69) in arm B. Gender M/F: Arm A 54/20 and 43/26 in arm B. ISS stage III 51 (68.9%) arm A vs 44 (63.8%) arm B. Serum LDH raised to &gt;250 u/L was observed in 25 (44.6%) vs 31 (52.5%) in arms A and B, p=0.4. Revised staging including ISS and serum LDH at baseline: stage III 47 (81%) and 37 (65%) in arms A and B respectively. 14 (18.9%) and 19 (27.5%) of patients had light chain myeloma in arms A and B respectively. Overall response rates (sCR+CR+VGPR+PR) is 78.4% vs 73.9% in arms A and B respectively, p=0.6; sCR + CR 21 (28.4%) and 21 (30.4%) respectively, p=0.86. Median follow-up 17.1 months (range 1 to 33). Median overall survival (OS) is 30.2 months (95% CI 28.2 to 32.2) and 28.6 months (95%CI 26 to 31.3) in arms A and B respectively, p=0.3. Median progression-free survival (PFS) was 27.8 months (95%CI 25.4 to 30.2) and 28 months (95%CI 24.6 to 31.4) respectively, p=0.3. Estimated one-year OS is 88% vs 85% in arms A and B, and PFS 83% vs 72%, respectively. Grade 3 anemia occurred in one patient in arm B, and grade 3 deep vein thromboses in one patient in arm A. One patient in arm A developed grade 4 myelosuppression leading to therapy change at the end of the first cycle. Conclusion: In this analysis - response rates and median progression-free survival are similar in both arms. Disclosures No relevant conflicts of interest to declare.

scholarly journals Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma

2020 ◽  
Vol 38 (30) ◽  
pp. 3494-3505 ◽  
Author(s):  
Amit M. Oza ◽  
Domenica Lorusso ◽  
Carol Aghajanian ◽  
Ana Oaknin ◽  
Andrew Dean ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Wild Type ◽  
Free Survival ◽  
Patient Subgroup ◽  
The Mean ◽  
Grade 3 ◽  
Experienced Grade

PURPOSE To investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo. PATIENTS AND METHODS Patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function × the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade ≥ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade ≥ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as μTOX × TOX + TWiST, with μTOX calculated using EQ-5D-3L data. RESULTS The visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA-mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade ≥ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA-mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade ≥ 2 TEAEs also consistently favored rucaparib. CONCLUSION The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.

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