Final Survival Results Research Articles

SOGUG-Vexillum: Phase II non-randomized clinical trial of nivolumab/ipilimumab maintenance following first-line chemotherapy in unresectable locally advanced or metastatic urothelial cancer.

4576 Background: Nivolumab (nivo) 1mg/kg plus ipilimumab (ipi) 3mg/kg achieved the highest ORR (42.4%) in refractory metastatic urothelial carcinoma (mUC) with a manageable safety profile. The addition of nivo and ipi subsequently to first-line chemotherapy (CT) could consolidate the clinical benefit. Methods: This single arm, open-label, multicenter study evaluates the effectiveness of ipi 3 mg/kg and nivo 1 mg/kg (Q3W) for 4 cycles followed by nivo maintenance therapy (Q4W) in delaying disease progression in patients with unresectable urothelial cancer that did not progress after first-line platinum-based CT (at least 4-6 cycles of CT). Autoimmune disease, immune deficiency, and symptomatic brain metastasis were excluded. The primary endpoint is Progression Free Survival (PFS) in intention-to-treat and PD-L1 populations. Secondary endpoints include: objective response rate (ORR), duration of response (DoR), overall survival (OS), overall survival from 1st dose of CT (cOS), progression-free survival from 1st dose of CT (cPFS), safety and translational biomarker analysis. Sample size was estimated using a Simon II stage design for 4-months PFS rate (H0= 40%; H1= 60; α= 0.05; β= 80%; attrition 10%), requiring 25 patients in the 1st stage and up to 66 in total. Here we report the interim analysis for 1st stage. Results: As of January 2024, the 1st accrual stage was completed with 25 evaluable patients. Baseline characteristics are outlined in the table. With a median follow-up of 6.8 months (95% CI: 6.2-10.5), the 4-m PFS rate was 64% (95% CI: 47.7-85.9) and the median PFS was 4.3 months (95% CI: 3.2-NR). The median cPFS was 9.4 months (95% CI: 8-NR). The 6-m OS rate was 76.4% (95% CI: 60-97.2), while median cOS was 15.4 months (95% CI: 15.4-NR). The median duration of treatment was 2.6 months (95% CI: 2.1, 5.7). Nivo and ipi were permanently discontinued due to toxicity in 3 (12%) and 1 (4.2%) patients, respectively. Nivo doses were delayed in 8 (32%) patients and ipi in 3 (12%) for management of toxicity. Grade ≥3 toxicities were reported in 8 (32%) patients, being the most common: Immune-mediated hepatitis (8%), ALT/AST increased (8%) and diarrhea (8%). Conclusions: Maintenance treatment with nivo and ipi showed preliminary efficacy consolidating clinical benefit to CT with a manageable safety profile. The 4-m PFS rate surpassed the futility threshold in the interim analysis and the accrual in Stage II is underway. Final survival results are awaited. Clinical trial information: NCT05219435 . [Table: see text]

Fruquintinib combined with sintilimab plus transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma: A single-arm phase II study.

499 Background: Tyrosine kinase inhibitor combined with immune checkpoint inhibitor has been reported a synergetic survival benefit in patients with unresectable hepatocellular carcinoma (uHCC). TACE induces tumor necrosis and tumor antigen release was believed to increase immune responses of anticancer immunotherapies. This study aimed to evaluate the safety and efficacy of fruquintinib combined with sintilimab plus TACE for uHCC. Methods: This study was a single-arm, open-label phase Ⅱ exploratory clinical study (NCT05971199). Eligible patients were China liver cancer stage (CNLC) Ⅱb-Ⅲa and not candidates for surgical resection or ablation, or liver transplantation, at least one target lesion evaluable, ECOG performance status of 0-1, and Child-Pugh score ≤7. Enrolled patients would receive treatment with TACE (TACE was repeated on demand, but < 5 times) followed by sintilimab 200 mg every 3 weeks and fruquintinib (5 mg QD, 2w on/1w off) until intolerable toxicity or disease progression. The primary endpoint was progression free survival (PFS). The secondary endpoints included adverse events (AEs), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) per mRECIST. Results: As of August 20, 2023, 15 enrolled patients with uHCC were treated. Mean follow-up time is 10.7 months. The median age was 58 years. At present, 10 patients were included for efficacy and safety analysis evaluation. Number of patients with CNLC stage Ⅱb and Ⅲa was 0 (0 %) and 15 (100 %), respectively. The median PFS and OS data are not yet mature. The ORR and DCR were 80% and 100% respectively based on mRECIST (1 CR, 10%; 7 PR, 70%; 2 SD, 20%). The most common (≥ 10%) TRAEs (≥ Grade 3) were elevated glutamic oxaloacetic transaminase, hypertension, proteinuria. No unexpected toxicity or treatment-related deaths occurred. Conclusions: Fruquintinib combined with sintilimab and TACE is a promising and tolerable therapeutic regimen for patients with CNLC Ⅱb-Ⅲa uHCC. This study is still ongoing and further follow-up is required to obtain final survival results. Clinical trial information: NCT05971199 .

Final survival results of ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in previously untreated HER2 positive esophago gastric adenocarcinoma: The randomized AIO INTEGA trial.

4026 Background: In metastatic esophagogastric adenocarcinoma (EGA), the addition of PD-1 inhibitors (i) to chemotherapy has improved the outcome in selected patient populations. The randomized INTEGA trial investigated trastuzumab and PD-1i with FOLFOX or CTLA-4i in 1st line treatment of advanced HER2+ EGA. Methods: Patients with previously untreated, metastatic HER2+ (local IHC3+ or 2+/ISH+) EGA, and adequate organ function were randomized to trastuzumab and nivolumab (1mg/kg Q3W x4 /240mg Q2W for up to 12 months) in combination with ipilimumab (3mg/kg x4 Q3W; Ipi arm) or mFOLFOX6 (FOLFOX arm) accompanied by a large translational program. The primary endpoint was the 12month overall survival (OS) rate. The trial was registered at ClinicalTrials.gov, NCT03409848. Results: Between March 2018 and May 2020, 97 patients were enrolled and 88 randomized across 21 German sites with the following baseline characteristics: female/male 18/70, median age 60.5 (range 41-80), ECOG 0/1 54/34, GEJ/stomach 66/22. Central post hoc biomarker analysis on 82 evaluable patients showed PD-L1 CPS≥1/≥5 in 59/46 patients and confirmed HER2 (central IHC3+ or 2+/ISH+) positivity in 77 patients. The observed OS rate at 12 months was 70% (95% confidence interval (CI) 54-81%) in the FOLFOX arm, and 57% (95% CI 41-71%) in the Ipi arm. The progression free survival was 10.7 and 3.2 months, and the overall response rate was 53.5% and 34% in the FOLFOX and the Ipi arm, respectively. Although these data are in favor of the FOLFOX arm, the overall survival curves crossed with increased follow-up (median follow-up of 18.8 months) and thus the final median OS was 22.1 and 23.3 months, numerically favoring the Ipi arm. According to the centrally assessed CPS the OS was: 22.1 and 32.2 months in the CPS<5 group, and 22.7 and 12.6 months in the CPS≥5 group for the FOLFOX and the Ipi arm, respectively. Notably, the median tumor burden calculated as the sum of target lesions was numerically lowest in the Ipi arm with higher than median OS. Conclusions: In contrast to limited short term efficacy of the Ipi arm as reflected by the lower PFS, the Ipi arm showed favorable OS, that was inversely correlated to the CPS status. Further analysis of baseline clinical and molecular data to better identify the subgroup of patients benefitting the most of trastuzumab/nivolumab/ipilimumab will be presented at the meeting. Clinical trial information: NCT03409848 . [Table: see text]

Early efficacy results from atezolizumab (ATZ) with split doses of cisplatin plus gemcitabine in patients with locally advanced or metastatic urothelial carcinoma (SOGUG-AUREA).

502 Background: Urothelial carcinoma (UC) commonly affects patients (pts) who are ineligible for full doses of cisplatin-based chemotherapy (CT) due to bad performance status, advanced age, or renal impairment. The combination of split-dose cisplatin with ATZ might be a feasible treatment for pts with UC who are unfit for full doses of cisplatin. Methods: The phase II SOGUG-AUREA clinical trial recruited treatment-naive pts in advanced or metastatic settings considered unfit for full dose of platinum-based CT. Pts received a split dose of cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) days 1 and 8 (up to 6 cycles) in combination with 3-weekly ATZ 1200 mg in D1 intravenously until progression, unacceptable toxicity, or absence of clinical benefit. Here we present the early results from the confirmed objective response rate (ORR) according to RECIST 1.1, the primary endpoint for efficacy, progression-free survival (PFS), overall survival (OS) and safety. Results: Between Jan 2021 and Mar 2022, 82 pts were screened, 66 pts were enrolled and received at least one dose of study treatment. Baseline characteristics are outlined in the table. The median duration of ATZ treatment was 4.4 months (m) (95%CI: 4.1-4.6). The confirmed ORR was 40.9%, with 5 (7.6%) pts having CR and 22 (33.3%) PR. The median duration of the response was 7 m (95%CI: 4.9-10.4). The clinical benefit rate (CBR) was 53%, and SD (maintained > 6m) was reported in 8 (12.1%) pts. Eight (12.1%) pts were not evaluable for response due to exitus previous to disease evaluation (9.1%), non measurable target lesions (1.5%) or withdrawal (1.5%). With a median follow-up of 9.3 m (range: 0.6-18.1), the median PFS was 6.9 m (95%CI: 6.4-9.2), with a 6-m PFS rate of 67.1% (95% CI: 56.5-79.7). The reasons for platinum ineligibility did not correlate with PFS. The 6-m OS rate was 78.2% (95%CI: 68.6-89). Most frequent grade 3-4 toxicities were neutrophil count decreased (24.2%), anemia (21.5%) and platelet count decreased (13.6%). Conclusions: ATZ with split doses of CT was safely administered in a population of frail pts with mUC who were unfit for CT showing promising preliminary survival outcomes in terms of response. Final survival results are awaited. Clinical trial information: NCT04602078 . [Table: see text]

Sorafenib plus tislelizumab as maintenance therapy for patients with advanced hepatocellular carcinoma treated with transarterial chemoembolization: A phase II study.

574 Background: Tyrosine kinase inhibitor combined with immune checkpoint inhibitor has been reported to confer a survival benefit in patients with unresectable hepatocellular carcinoma (HCC). This phase II study (NCT04599777) aimed to evaluate the safety and efficacy of sorafenib plus tislelizumab (Sor-Tis) for patients with advanced HCC who received transarterial chemoembolization (TACE). Methods: The key inclusion criteria were: age ≥ 18 years; BCLC C stage HCC; no prior systemic therapy; Child-Pugh score ≤7; ECOG PS ≤1. The key exclusion criteria were: tumor thrombus involving the main portal vein or vena cava; central nervous system metastasis; history of malignancies other than HCC; history of organ and stem cell transplantation. Sorafenib (400 mg Bid) and tislelizumab (200 mg Q3W) was started at 3-7 days after the first TACE (TACE was repeated on demand). The primary endpoint was overall survival (OS). The secondary endpoints included treatment-related adverse events (TRAEs), progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: Thirty patients were enrolled in this study. Among these patients, 27 (90.0%) had macrovascular invasion, 12 (40.0%) had extrahepatic metastasis and 14 (46.7%) had intrahepatic tumor number >3. The mean largest tumor diameter was 11.4±3.9 cm. Till cutoff date (September 15th, 2022), the mean follow-up for the patients was 16.6±3.8 months. The median OS was not reached. The ORR per RECIST 1.1 and mRECIST was 20.0% and 53.3%, respectively. The DCR per RECIST 1.1 or mRECIST was 86.7%. During follow-up, 29 patients (96.7%) experienced disease progression (per RECIST 1.1 or mRECIST). The median PFS was 6.8 (95% confidence interval [CI] 4.5-9.0) months. TRAEs occurred in 28 patients (93.3%) and ≥grade 3 TRAEs was observed in 11 patients (36.7%). There was no treatment-related death in these patients. Conclusions: Sor-Tis showed preliminary clinical benefits and was tolerated in advanced HCC patients treated with TACE. This study is still ongoing and further follow-up is required to obtain final survival results. Clinical trial information: NCT04599777 .

Safety and efficacy of glasdegib in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma: Phase Ib/II GEINO 1602 trial.

2060 Background: Hedgehog signaling through Smoothened (SMO) protein in gliomas promotes cell cycle progression and leads to glioma stem cells (GSCs) maintenance, which constitutes one of the key hallmarks for glioblastoma (GB) resistance against anticancer therapies. Glasdegib, a SMO inhibitor, may disrupt GSCs and lead to enhanced efficacy of the Stupp scheme. Methods: Newly diagnosed GB pts received glasdegib with standard radiotherapy (RT)/ temozolomide (TMZ) followed by maintenance with glasdegib monotherapy. The primary objective was to determine the recommended phase 2 dose (RP2D) in a 3+3 dose escalation (DE) strategy in phase Ib and overall survival (OS) in phase II. Secondary objectives included progression-free (PFS) according to RANO criteria, safety, changes in performance status, and exploratory biomarker analysis. Results: Between 2018 and 2020, 79 GB pts were enrolled and 78 received at least one dose of glasdegib. In DE, 4 pts received Glasdegib at 100 mg/QD and 6 pts received 75 mg/QD. DLTs were reported in 3/4 pts in 100 mg dose level, and 1/6 pts in 75 mg dose level, declaring 75 mg/QD of glasdegib as RP2D. For phase II, 68 additional pts were treated at 75 mg/QD dose. The median age was 55 years (range: 28-78), 54% were male, 45% were MGMT unmethylated, and 1 pts had an IDH1/2 mutation. Glasdegib treatment lasted a median of 6 m (range: 0.5-21.9). Overall, 72 (97.3%) pts completed concomitant therapy, 65 (87.8%) started adjuvant therapy, 28 (37.8%) completed adjuvant therapy, and 23 (31.1%) continued glasdegib monotherapy. Treatment combination was discontinued due to treatment-related adverse events (TRAEs) in 9 (12.2%) pts. For those pts that received RT/TMZ combined with glasdegib at 75 mg/QD dose, 7 (9.5%) presented grade (G) ≥3 hematological TRAEs during concomitant treatment and 2 (3.1%) during the adjuvant treatment. There were no G≥3 TRAEs of any type during the maintenance phase. Neutrophil count decrease G≥3 was reported in 6 (8.1%) pts and platelet count decrease G≥3 in 7 (9.5%) pts. Cutaneous events G≥3 were reported in 3 (4.1%) pts. ECOG, Minimental and Barthel indexes, were maintained when comparing baseline with end of treatment (p = 0.181, 0.25 and 0.346 respectively). Stabilization was the most common response, reported in 60 (81.1%) pts. After a median follow up of 7.8 m (range 0.7-25.9), median PFS was 6.9 m (95% CI: 6.1-8.5). The 6-m PFS rate was 62.1% (95% CI: 50.9-75.8) and the 18 m OS rate was 63.3% (95% CI: 47.5-84.4). Conclusions: The addition of glasdegib to standard RT and TMZ was safe. Glasdegib monotherapy showed no G ≥3 TRAEs. Most patients had disease stabilization, with a promising preliminary PFS and OS for newly diagnosed GBM. Final survival results are awaited. Clinical trial information: NCT03466450.

Sintilimab plus bevacizumab as maintenance therapy for patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization: A phase Ib study.

e16165 Background: Sintilimab (a PD-1 inhibitor) plus bevacizumab (Sin-Bev) has been demonstrated to confer a significant survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). This phase Ib study (NCT04592029) aimed to evaluate the safety and efficacy of Sin-Bev for patients with uHCC who received transarterial chemoembolization (TACE). Methods: The key eligibility criteria were: age ≥ 18 years; BCLC B/C stage uHCC; no prior systemic therapy and non-curative local treatments; Child-Pugh score ≤7; ECOG PS ≤1. This study included dose escalation and dose expansion stages. In the dose escalation stage, a 3+3 design was employed to determine the safety of a standard dose of sintilimab (200 mg Q3W) plus two possible doses of bevacizumab (group A: 7.5 mg/kg Q3W; group B: 15.0 mg/kg Q3W) after TACE. In the dose expansion stage, additional 30 patients were randomized 1:1 to each group. Sintilimab and bevacizumab was started at 3-7 days after the first TACE (TACE was repeated on demand). The primary endpoints were the incidence of adverse events (AEs) and progression free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: At the time of data cutoff (January 20th, 2022), 36 patients were enrolled (18 in each group). One patient in group A withdrew from the study after the first cycle of treatment. Of the remaining 35 patients, 20 (57.1%) had disease at BCLC C stage, 15 (42.9%) had macroscopic vascular invasion and 11 (31.4%) had extrahepatic metastasis. The mean largest tumor size was 10.5±5.2 cm. The median follow-up was 9.57 (range, 4.4-15.6) months. Thirty-one patients (86.1%, n=36) had treatment-related AEs (83.3% in group A vs. 88.9% in group B, P=1.000). All the AEs were mild (<grade 2) and manageable. During follow-up, 19 patients (54.3%) experienced disease progression (per RECIST 1.1 or mRECIST). The median PFS was 7.2 (95% CI 3.6-10.8) months (6.7 [95% CI 4.7-8.8] months in group A vs. 8.4 [95% CI 3.9-12.8] months in group B, P=0.832). The median PFS in this report was immature due to some later enrolled patients were censored. Thus, it is likely to improve with longer follow-up. The ORR per RECIST 1.1 and mRECIST was 37.1% (41.2% in group A vs. 33.3% in group B, P=0.733) and 80.0% (88.2 in group A vs. 72.2% in group B, P=0.402), respectively. The DCR per RECIST 1.1 or mRECIST was 91.4% (94.1% in group A vs. 88.9% in group B, P=1.000). The median OS was not reached. Conclusions: Sin-Bev showed preliminary clinical benefits and an acceptable safety profile in uHCC patients treated with TACE. The study is still ongoing and further follow-up is required to obtain the final survival results. Clinical trial information: NCT04592029.

Abstract P2-13-04: Final survival analysis of a phase 3 study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer

Abstract Background: SB3 (trastuzumab-dttb) is a biosimilar approved globally based on its similarity with reference trastuzumab (TRZ) demonstrated by thorough comparability exercises in analytical, biological, and clinical studies. In a randomized, double-blind, multicenter Phase 3 study of 875 patients with HER2-positive early or locally advanced breast cancer in the neoadjuvant setting, equivalent efficacy, similar safety, pharmacokinetics, and immunogenicity between SB3 and TRZ were shown. However, when quality attributes of TRZ were examined, downward drifts in antibody-dependent cell-mediated cytotoxicity activities (ADCC) were observed in the TRZ lots with expiry dates ranging from Aug 2018 to Dec 2019. Some of these lots of the reference product were found to be used in the Phase 3 study. After completing the Phase 3 study, patients from select countries were included in a follow-up observational study to monitor cardiac safety and survival. Here, we report the final survival results, including post-hoc subgroup analysis based on ADCC status, at a median follow-up of 68 months. Methods: During the follow-up observational study, the protocol was amended to include additional patients who originally were enrolled in the Phase 3 study but had not been followed in the observational study, in order to collect a larger sample of survival data. For these additional patients, medical records from the last assessment in the Phase 3 study through the date of enrollment in the follow-up study were collected retrospectively. As post-hoc analysis, patients in the TRZ arm were stratified into two subgroups: patients who received during neoadjuvant treatment at least one vial of TRZ with downward drift in ADCC as “Drifted TRZ”, and the others as “Non-drifted TRZ”. Event-free survival (EFS) and overall survival (OS) were assessed. Results: Of 875 patients randomized in the Phase 3 study, 538 patients (SB3, N=267; TRZ, N=271) were enrolled in the follow-up observational study: 367 patients were initially enrolled in the follow-up study, and 171 patients were additionally enrolled following the protocol amendment. The median follow-up duration was 68 months from randomization in the Phase 3 study. 54 events (20.2%) in the SB3 arm, and 67 events (24.7%) in the TRZ arm were reported (HR 0.84 [0.58, 1.20], p=0.335). 22 deaths (8.2%) and 38 deaths (14%) were reported in SB3 and TRZ arms, respectively (HR 0.61 [0.36, 1.05], p=0.073). In post-hoc analysis, of 271 patients in TRZ arm, 107 patients were grouped as “Non-drifted TRZ”, and 164 patients as “Drifted TRZ”. 19 events (17.8%) in the Non-drifted TRZ group and 48 (29.3%) events in the Drifted TRZ group occurred (HR 2.57 [1.28, 5.14], p=0.008). 9 deaths (8.4%) in the Non-drifted TRZ group and 29 deaths (17.7%) in the Drifted TRZ group were reported (HR 3.87 [1.37, 10.93], p=0.011). No difference was observed between SB3 arm and Non-drifted TRZ group in terms of EFS (HR 1.28 [0.73, 2.22], p=0.391) and OS (HR 0.99 [0.42, 2.31], p=0.975). Conclusions: Comparable long-term efficacy results in EFS and OS were shown at 68 months of follow-up, further supporting biosimilarity of SB3 to the reference product. Currently, these follow-up results represent the longest monitoring data of patients treated with a trastuzumab biosimilar for HER2-positive early or locally advanced breast cancer. Citation Format: Xavier Pivot, Mark D Pegram, Javier Cortes, Diana Lüftner, Gary H Lyman, Giuseppe Curigliano, Igor M Bondarenko, Mikhail Dvorkin, Jin Hee Ahn, Seock-Ah Im, Maria Litwiniuk, Yaroslav V Shparyk, Gwo Fuang Ho, Nikolay V Kislov, Marek Wojtukiewicz, Tomasz Sarosiek, Yee Soo Chae, Jin Seok Ahn, Hyerin Jang, Sujung Kim, Jiwon Lee, Soo Young Lee, Ye Chan Yoon. Final survival analysis of a phase 3 study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-04.

Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).

5516 Background: SPARTAN evaluated APA vs PBO in pts with nmCRPC and a prostate-specific antigen doubling time of ≤ 10 mo receiving androgen deprivation therapy (ADT). At primary end point analysis of metastasis-free survival (MFS), APA significantly improved median MFS by 2 yrs, as well as time to metastasis, progression-free survival, and time to symptomatic progression vs PBO (Smith, et al. NEJM 2018); overall survival (OS) results were immature. SPARTAN was unblinded upon meeting the primary end point; pts still on PBO were allowed to cross over to APA. Final survival results are reported herein. Methods: 1207 nmCRPC pts were randomized 2:1 to APA (240 mg QD) or PBO plus ongoing ADT. At progression, pts could receive open-label sponsor-provided abiraterone acetate + prednisone. After the primary efficacy end point (MFS) was met, 76 PBO pts (19%) crossed over to APA. OS and time to cytotoxic chemotherapy (TTCx) were tested by group sequential testing procedure with O’Brien-Fleming (OBF)-type alpha spending function. Time-to-event end points were analyzed by Kaplan-Meier method and Cox model. A sensitivity analysis for OS, accounting for crossover using a naïve censoring approach, was conducted. Results: With follow-up of 52.0 mo, 428 (of 427 required) OS events had occurred. Median treatment duration: APA, 32.9 mo; PBO, 11.5 mo. Median OS was significantly longer with APA + ADT vs PBO + ADT (73.9 vs 59.9 mo), (hazard ratio [HR], 0.784, Table). APA significantly lengthened TTCx (HR, 0.629). Discontinuation rates (APA vs PBO) due to progressive disease were 42.7% vs 73.9%, and due to adverse events (AE) 15.2% vs 8.4%. Safety was consistent with previous reports; grade 3/4 treatment-emergent (TE) AEs of special interest were rash 5.2%, fractures 4.9%, falls 2.7%, ischemic heart disease 2.6%, hypothyroidism 0%, and seizures 0%. 1 TEAE leading to death (myocardial infarction) was considered potentially APA related. Conclusions: In pts with nmCRPC, APA + ADT significantly improved OS compared with PBO + ADT, with median OS > 6 yr in the APA + ADT group and 14 mo improvement over PBO + ADT. Benefit from APA was observed despite a 19% crossover from PBO. The safety profile of APA was consistent with prior interim analyses. Clinical trial information: NCT01946204 . [Table: see text]

1487P - LURET: Final survival results of the phase II trial of vandetanib in patients with advanced RET-rearranged non-small cell lung cancer

1487P - LURET: Final survival results of the phase II trial of vandetanib in patients with advanced RET-rearranged non-small cell lung cancer

ISY-17-5 - Final survival results of a multicenter phase I/II study of TAS-102 with bevacizumab for mCRC (C-TASK FORCE)

ISY-17-5 - Final survival results of a multicenter phase I/II study of TAS-102 with bevacizumab for mCRC (C-TASK FORCE)

PD-014 Final survival results and onset of neutropenia as an indicator of therapeutic effect in phase 2 of TAS-102 vs placebo with metastatic colorectal cancer (J003-10040030)

PD-014 Final survival results and onset of neutropenia as an indicator of therapeutic effect in phase 2 of TAS-102 vs placebo with metastatic colorectal cancer (J003-10040030)

PD-013 Final survival results of a multicenter phase I/II study of TAS-102 with bevacizumab for metastatic colorectal cancer patients refractory to standard therapies (C-TASK FORCE)

PD-013 Final survival results of a multicenter phase I/II study of TAS-102 with bevacizumab for metastatic colorectal cancer patients refractory to standard therapies (C-TASK FORCE)

TAS-102 versus placebo plus best supportive care in patients with metastatic colorectal cancer refractory to standard therapies: Final survival results of the phase III RECOURSE trial.

634 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer refractory/intolerant to standard therapies were evaluated in the RECOURSE trial. Original results of RECOURSE based on the cut-off date of January 24, 2014, in which 72% of mortality events had occurred, demonstrated a significant improvement in overall survival (OS) with TAS-102 vs placebo. Here we report results of an updated survival analysis from RECOURSE and a retrospective analysis of OS outcomes based on a clinical prognostic risk index. Methods: Patients were randomized 2:1 to receive TAS-102 or placebo. Study treatment continued until disease progression, death, or unacceptable toxicity. The primary endpoint was OS; final survival data were collected on October 8, 2014. A clinical OS prognostic risk score was assessed to evaluate OS effect in patients from low to high prognostic score. Prognostic factors contributing to the risk index were from those prespecified in the multivariate modeling assessment of OS outcome. Results: At data cut-off for the final survival analysis, 89% of the 800 patients randomly assigned to TAS-102 or placebo had died, accounting for 138 events in addition to 574 (72%) events included in the original analysis. The updated results for OS are shown in the Table. Conclusions: An updated survival analysis confirmed that OS benefit with TAS-102 was maintained and increased to a full 2 months; improvement in 1-year survival surpassed 10% in these heavily pretreated patients. OS benefit appears to be maintained for all patients in the trial regardless of prognostic status at trial entry. Clinical trial information: NCT01607957. [Table: see text]

A randomized Phase 3 study comparing first-line pemetrexed plus cisplatin followed by gefitinib maintenance (PC/G) with gefitinib monotherapy (G) in East Asian patients (pts) with locally advanced or metastatic nonsquamous non-small cell lung cancer (nSqNSCLC): Final survival results.

8041 Background: The primary analysis of this open-label, randomized, multicenter study found no significant difference in progression-free survival (PFS) between PC/G and G in pts with nSqNSCLC and unknown epidermal growth factor receptor (EGFR) mutation status, although the unadjusted hazard ratio (HR, PC/G vs G) favored PC/G (0.85, 95% CI: 0.63–1.13). Final overall survival (OS) data are reported here. Methods: Eligible pts were chemonaive, East Asian light ex-smokers/never-smokers aged ≥18 years with advanced nSqNSCLC, ECOG PS 0/1 and unknown EGFR mutation status. Pts (N = 236) were randomized (1:1) to PC/G (pemetrexed 500 mg/m2 + cisplatin 75 mg/m2for six 21-day cycles then gefitinib 250 mg/day) or G (gefitinib 250 mg/day). EGFR mutation status was determined for 76 pts; 52 (68.4%) had mutations. OS was analyzed (intent-to-treat population) by unadjusted Cox regression analysis. Results: Baseline characteristics were similar between groups (both N = 118). Median OS was similar in the PC/G and G group...

Adjuvant gemcitabine for high-risk breast cancer (BC) patients: Final survival results of the randomized phase III SUCCESS-A study.

1010 Background: Gemcitabine (G) has shown to have a relevant single agent efficacy and to improve chemotherapy response to taxanes in advanced BC patients. Aim of this study was to evaluate the ef...

Conclusion

Future OncologyVol. 9, No. 12s Symposium PaperConclusionJalid SehouliJalid SehouliDepartment of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité University Hospital, Berlin, Germany. Search for more papers by this authorEmail the corresponding author at sehouli@aol.comPublished Online:6 Nov 2013https://doi.org/10.2217/fon.13.200AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View article"Conclusion." , 9(12s), p. 41Keywords: fully platinum-sensitivemechanism of actionovarian cancerpartially platinum-sensitivepegylated liposomal doxorubicintrabectedinReferences1 Monk BJ, Herzog TJ, Kaye SB et al. Final survival results of the randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer. J. Clin. Oncol.29(Suppl.), Abstract 5046 (2011).Crossref, Medline, Google Scholar2 Aghajanian C, Nycum LR, Goff B, Nguyen H, Husain A, Blank SV. Updated overall survival analysis in OCEANS, a randomized Phase 3 trial of gemcitabine + carboplatin and bevacizumab or placebo followed by bevacizumab or placebo in platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Presented at: the European Society for Medical Oncology (ESMO). Vienna, Austria, 28 September–2 October 2012.Google ScholarFiguresReferencesRelatedDetails Vol. 9, No. 12s eToC Sign up Follow us on social media for the latest updates Metrics Downloaded 21 times History Published online 6 November 2013 Published in print December 2013 Information© Future Medicine LtdKeywordsfully platinum-sensitivemechanism of actionovarian cancerpartially platinum-sensitivepegylated liposomal doxorubicintrabectedinFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Editorial assistance was provided by Content Ed Net, with funding from PharmaMar, Madrid, Spain.PDF download

Management strategies for recurrent platinum-resistant ovarian cancer.

Although ovarian cancer is often a chemosensitive malignancy, patients who are resistant to platinum-based chemotherapy represent a therapeutic challenge. Currently, the only drugs that are US FDA approved to treat this subset of patients are paclitaxel, pegylated liposomal doxorubicin (PLD) and topotecan. The response rates with these agents is in the 10-15% range and overall survival is around 12 months. Other drugs that have shown some activity in platinum-resistant ovarian cancer include the taxane analogues, oral etoposide, pemetrexed and bevacizumab. Unfortunately, randomized phase III trials of second-line chemotherapy in patients with platinum-resistant ovarian cancer have not shown an advantage over existing therapy with respect to progression-free survival or overall survival. The only trial that has reported a significant progression-free survival advantage over standard therapy is a randomized phase II trial of PLD with or without EC145, a folate-linked vinca alkaloid. Final survival results of this trial are pending.

Final survival results of the randomized phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer.

5046 Background: Trabectedin (T) in combination with pegylated liposomal doxorubicin (PLD) was demonstrated to improve progression-free survival (PFS) and overall response rate (ORR) in comparison to PLD alone as a second-line treatment of recurrent ovarian cancer (J Clin Oncol 28:3107-14, 2010). We report the protocol defined final analysis of overall survival (OS). Methods: Women ≥18 years, stratified by performance status (0-1 vs 2) and platinum-free interval (PFI) <6 vs > 6 months(m), were randomly assigned to receive an IV infusion of PLD 30 mg/m2 followed by a 3-hour infusion of T 1.1 mg/m2 every 3 weeks or PLD 50 mg/m2 every 4 weeks. The primary endpoint was PFS by independent radiology assessment and secondary endpoints included OS and ORR. Results: The final OS analysis was performed on 12 Nov 2010. The median follow-up was 47.4m. Among the 672 randomized subjects, 522 (77.7%) deaths were observed (258 in the T+PLD arm and 264 in the PLD arm). The median OS for T+PLD and PLD arms was 22.2 and 18.9m, respectively (HR= 0.86; 95%CI: 0.72, 1.02; p=0.0835 [unstratified log-rank test]). There was an unanticipated imbalance in the PFI between the two arms favoring the PLD arm (mean PFI: PLD=13.3m, T+D=10.6m. To provide a better estimate of the true treatment effect of adding T to PLD, a multivariate analysis adjusted for key prognostic factors (including PFI) was performed which demonstrated a significant improvement in OS in subjects treated with the combination (HR=0.82; 95%CI: 0.69,0.98; p=0.0285). Consistent improvement in OS was seen across all PFI subgroups, which was more pronounced in 6-12PFI subgroup (Table). Conclusions: T+PLD combination showed an improvement in OS in recurrent ovarian cancer compared with PLD alone. Randomized trials of T+PLD versus platinum combinations are indicated. Subgroup analysis by PFI. Subgroup by PFI (m) Median PLD (m) Median T+PLD (m) HR (95%CI) 0-6 12.3 14.2 0.94 (0.71, 1.25) 6-12 16.4 22.4 0.64 (0.47, 0.86) >12 31.7 36.5 0.83 (0.59, 1.16)

Phase I study of the IXO regimen, irinotecan (I), capecitabine (X), oxaliplatin (O), as first-line therapy for metastatic colorectal cancer: Final survival results

4082 Background: This study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of the IXO regimen when used as first-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients with ECOG PS 0–2, histologically proven, chemo-naïve, non-resectable mCRC were eligible. Phase I starting doses were as follows: I (180 mg/m2 i.v.) d1, X (850 mg/m2 bid orally) d2–15, O (85 mg/m2 i.v.) d1; q3w. Dose escalation (3+3 design) was based on toxicity observed at previous dose levels (DL) until DLT and the MTD were reached. Results: 39 pts (31 male/8 female, median age 58 years, ECOG PS 0–1 in 37, 95%) received a median of 11 cycles (range 1–34) at 8 DLs. 39 pts were evaluable for toxicity. The most common grade 3/4 hematological adverse events (AEs) were granulocytopenia (60%) and fever/febrile neutropenia (18%). The most common grade 3 non-hematological AEs were diarrhea (15%), vomiting (10%), fatigue (8%). No grade 3/4 neuropathy was reported. DLTs: 1 DLT was observed at each of the first 4 DLs, no DLTs at DL5 &amp; 6, 1 at DL7 and 2 at DL8. MTD was reached at DL8. The recommended phase II dose (DL7) is as follows: I (160 mg/m2), X (950 mg/m2), O (100 mg/m2). Efficacy: 38 pts are evaluable for efficacy. The RR is 74% (95% CI 60–89), including 4 CRs, 25 PRs and 6 SDs. The disease control rate is 90% (95% CI 80–100). 10 (26%) pts had subsequent liver surgery with curative intent; 1 had lung resection. Median progression-free survival was 12.3 months (95% CI, 8–17). Overall median survival was 26.4 months (95% CI, 13–36). Conclusions: Diarrhea is the main DLT. Severe neutropenia was of short duration and manageable. The IXO regimen is well tolerated and highly effective as first-line treatment for mCRC. It appears to be particularly effective in downsizing of initially unresectable colorectal cancer liver metastases. A phase II study to confirm the efficacy/safety of IXO in combination with bevacizumab (Avastin) is ongoing. Supported by: Hoffmann La-Roche, Sanofi-Aventis, Pfizer Canada. [Table: see text]