Phase II study for the evaluation of efficacy of pembrolizumab (MK-3475) in patients with cancer of unknown primary.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3103-TPS3103 ◽  
Author(s):  
Gauri R. Varadhachary ◽  
Kanwal Pratap Singh Raghav ◽  
Shubham Pant ◽  
Filip Janku ◽  
Siqing Fu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Cancer Of Unknown Primary ◽  
Unknown Primary ◽  
Progression Rate ◽  
Pathologic Evaluation ◽  
Recist 1.1 ◽  
Imaging Characteristics

TPS3103 Background: Cancer of unknown primary is a biopsy proven malignancy for which an anatomic primary remains unidentified after a focused search. It accounts for 3-4 % of all solid cancers and most investigators limit it to epithelial and undifferentiated cancers. Patients with metastatic melanoma and sarcoma are excluded. Sophisticated imaging, robust pathologic evaluation including immunostains, and genomic and proteomic characterization of these cancers have challenged the management of CUP. The paradigm has shifted from empiric platinum based combination doublets to a personalized approach. Nevertheless, without an anatomic primary, clinical trial opportunities are limited. There remains an unmet research need to evaluate the role of immunotherapy, specifically checkpoint blockade drugs in specific subsets of CUP patients. Methods: Adult Patients ≥ 18 years of age with ECOG PS 0-1, must meet the definition of a CUP cancer. Patients must be intolerant and/or refractory to at least one line of established therapy known to provide clinical benefit for their condition within the last 6 months (often, a platinum based therapy for carcinomas). Patients must have either measurable (RECIST 1.1) or evaluable disease. Although not limited to subtypes, there is a signficant interest in enrolling patients with isolated disseminated lymphadenopathy, HPV (+) CUP and those who have an IHC profile of those known cancers for which anti-PD therapy has been approved (lung, renal, others) The primary objective of this trial is to evaluate efficacy by evaluation of non-progression rate (NPR) at 27 weeks (9 cycles) as defined as the percentage of CUP patients who are alive and progression-free at 27 weeks (9 cycles) as assessed by RECIST 1.1. Secondary objectives include evaluating safety and tolerability of pembrolizumab (MK-3475); correlating efficacy, non-progression rate (NPR) at 27 weeks (9 cycles), objective response (CR or PR), progression-free survival (PFS), overall survival (OS) and duration of response (DOR) to PD-L1 status; and identifying imaging characteristics associated with immunological changes in tumor following treatment with pembrolizumab. Enrollment is ongoing. Clinical trial information: NCT02721732.

Evolve: A post PARP inhibitor clinical translational phase II trial of cediranib-olaparib in ovarian cancer—A Princess Margaret Consortium – GCIG Phase II Trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5521-5521 ◽  
Author(s):  
Stephanie Lheureux ◽  
Ana Oaknin ◽  
Swati Garg ◽  
Jeffrey Bruce ◽  
Neesha C. Dhani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Tumor Biopsy ◽  
Ps Ii

5521 Background: PARP inhibitors (PARPi) are approved therapies in high grade serous ovarian cancer (HGSOC). There are few studies after PARPi progression and correlation with dynamic changes in resistance. We hypothesized that PARPi resistance could be overcome by adding an anti-angiogenic. Methods: We report the first phase 2 trial assessing the combination of olaparib and cediranib after PARPi failure in HGSOC. This investigator initiated study included three cohorts of 10 evaluable patients (pts): i) platinum sensitive post PARPi (PS), ii) platinum resistant post PARPi (PR) and iii) exploratory cohort of pts re-challenged with chemotherapy post PARPi progression (PE) (NCT02681237). The primary objective was to determine objective response rate by RECIST v1.1 and progression free survival (PFS) at 16 weeks. Secondary objectives were to evaluate safety, PFS, overall survival (OS) and mechanisms of PARPi resistance. Pts who had radiographic progression on any PARPi were eligible. Archival tumor at initial diagnosis and baseline tumor biopsy at PARPi progression were mandatory. Pts received olaparib tablets 150mg BID with cediranib 20mg QD until progression or unacceptable toxicity. CT scans were performed every 8 weeks. Whole exome and RNA sequencing were performed on paired tumors tissues. Results: Thirty-four pts were enrolled. BRCA1/2 mutations were found in 9/11 PS, 8/10 PR and 7/13 PE pts. By RECIST1.1, four partial responses were observed (2 in PR and 2 in PE cohorts) and 18 stable disease. The 16−week PFS was 54.5% (31.8−93.6) in PS, 50% (26.9−92.9) in PR and 36% (15.6−82.8) in PE, respectively. OS at 1 year was 81.8% (61.9−100) in PS, 64.8% (39.3−100) in PR and 39.1% (14.7−100) in PE. Main related adverse events were anemia, hypertension, diarrhea and fatigue, grade 3 < 10%. Molecular analyses identified different mechanisms of PARPi resistance in ~77% of evaluable pts with matched pre-post PARPi progression biopsies such as reversion mutations in BRCA1/2 and other homologous repair (HR) genes; BRCA, HR and MDR upregulation, CCNE amplification and RIG-I like receptor downregulation. Conclusions: Treatment with olaparib-cediranib after PARPi failure was feasible and met the predefined bar for efficacy in each cohort. This is the largest clinical trial prospectively evaluating PARPi failure and correlating tissue genomic mechanisms of resistance. Clinical trial information: NCT02681237.

LENVAGIST - A multicenter, comparative, placebo-controlled, double-blinded, phase II study of the efficacy of lenvatinib in patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS11568-TPS11568
Author(s):  
Axel Le Cesne ◽  
Claire Cropet ◽  
Julien Gautier ◽  
Stéphanie Gagne ◽  
Katia Francourt ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Differentiated Thyroid Carcinoma ◽  
Primary Objective ◽  
Rank Test ◽  
Recist 1.1 ◽  
Double Blinded

TPS11568 Background: GastroIntestinal Stromal Tumors (GIST) are paradigmatic models of cancers with a driver mutation of an oncogene, in which imatinib is recommended as adjuvant therapy or treatment of locally advanced and metastatic forms. After failure of imatinib (either progression or toxicity), sunitinib and regorafenib are indicated as 2nd and 3rd lines, respectively. Beyond approved drugs, tyrosine kinase inhibitors (TKI) can bring clinical benefit because some clones remain sensitive to TKI. Lenvatinib is a broad spectrum TKI targeting KIT, RET, PDGFRA, VEGFR 1-3 and FGFR 1-4, that is approved in the treatment of differentiated thyroid carcinoma and metastatic renal cell carcinoma and hepatocellular carcinoma. Methods: This prospective, randomized, placebo-controlled, double-blinded, multicenter trial evaluates the efficacy and safety of Lenvatinib in adult GIST patients (pts) who failed at least to previous imatinib and sunitinib. Seventy-four pts will be randomly allocated in a 1:1 ratio to receive either oral lenvatinib, at a daily dose of 24mg, or its matching placebo, continuously, until progression of disease (PD) or unacceptable toxicity. Randomization will be stratified according to the number of different previous anticancer drugs (2 or > 2). The primary objective is to compare the Progression-free survival (PFS) between arms. The expected median PFS are 1.5 month in the control arm and 3.0 months in the experimental arm (HR = 0.5). Seventy one events will provide 90% power to show significant improvement in PFS, using a 2-sided log-rank test at a 10% level. Secondary endpoints include the overall survival, the objective response rate, the best overall response, the quality of life and the safety profile. Patients allocated in the placebo arm who experience PD (RECIST 1.1) may switch to active lenvatinib. Radiological endpoints will be evaluated using the RECIST 1.1. Translational objectives will be to identify blood and tumor parameters as predictive markers of lenvatinib efficacy. Recruitment has been activated in January 2020. Ten participating sites of the French Sarcoma Group will participate in the trial. Clinical trial information: NCT04193553 .

Phase Ib study of talimogene laherparepvec (T-VEC) injection into liver metastases (LMs) in combination with intravenous (IV) atezolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or colorectal cancer (CRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS725-TPS725
Author(s):  
J. Randolph Hecht ◽  
Arlene Chan ◽  
Miguel Martin ◽  
Nicolas Mach ◽  
Sara A. Hurvitz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Intralesional Injection ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
The Usa

TPS725 Background: T-VEC is a genetically modified, oncolytic herpes simplex virus type 1 designed to selectively replicate within tumors and produce GM-CSF to enhance systemic antitumor immune responses. Atezolizumab is a monoclonal antibody checkpoint inhibitor (CPI) that targets PD-L1. The safety of intrahepatic administration of T-VEC has been demonstrated in a prior clinical trial (NCT02509507). A previous trial of T-VEC in combination with a CPI in advanced melanoma demonstrated improved responses compared to those with a CPI alone (Puzanov et al. JCO. 2016; 34:2619-26). We hypothesize that T-VEC combined with a CPI may also be effective in other tumor types. This phase 1b, multicenter study evaluates the safety of intrahepatic injection of T-VEC in combination with IV atezolizumab in pts with TNBC or CRC with LMs. Methods: The study will enroll up to 36 pts in two parallel cohorts (18 TNBC, 18 CRC) at sites in the USA, Europe, and Australia. The primary objective is to evaluate the incidence of dose-limiting toxicities (DLTs). Secondary objectives include objective response rate, lesion-level responses in injected and uninjected tumors, progression-free survival, and overall survival. Key eligibility criteria include age ≥ 18 years, confirmed diagnosis of TNBC or CRC with LMs, ECOG performance status 0/1, adequate organ function, disease progression during or after ≥ 1 prior standard-of-care systemic therapy for metastatic disease, and ≥ 1 measurable, injectable LM. T-VEC will be given by image-guided intralesional injection of up to 4 mL of 106 plaque forming units (PFU)/mL on day 1 and up to 4 mL of 108 PFU/mL every 21 days thereafter; atezolizumab 1,200 mg IV will be given on day 1 and every 21 days thereafter. The DLT-evaluation period is the first two cycles (1 cycle = 21 days). Interim safety analysis will occur after the first 4–6 pts have become DLT evaluable. Up to six cycles of T-VEC will be given with an additional 6 cycles allowed. After cycle three, nonhepatic lesions may be injected, subject to protocol-defined criteria. The study opened for enrollment in January 2018. (NCT03256344) Clinical trial information: NCT03256344.

A multicenter, randomized, controlled phase II study: Efficacy and safety of PSMA-targeted radioligand therapy I-131-1095 (1095) plus enzalutamide (enza) in 18F-DCFPyL PSMA scan avid, metastatic castration-resistant prostate cancer (mCRPC) patients post-abiraterone (abi) progression (ARROW).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS187-TPS187
Author(s):  
A. Oliver Sartor ◽  
David Laidley ◽  
Frederic Pouliot ◽  
Stephan Probst ◽  
Robert Sabbagh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Open Label ◽  
Recist 1.1 ◽  
Modified Recist

TPS187 Background: PSMA is a transmembrane glycoprotein overexpressed in prostate cancer (PC) and further upregulated in castrate resistant disease. 1095 is a novel PSMA-targeted small molecule radioligand therapeutic that binds to the extracellular domain of PSMA selectively with high affinity, internalized, and delivers a targeted lethal radiation dose to PC cells. 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown robust diagnostic performance for detecting recurrent and metastatic PC. In the ARROW study, pts must demonstrate 18F-DCFPyL avidity prior to 1095 treatment. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at multiple sites in the US and Canada. Eligible male pts must have metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional doses administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Due to the COVID-19 pandemic, enrollment was halted in April 2020 but is reopening in October 2020. Clinical trial information: NCT03939689.

Differential response rates in early-phase cancer clinical trials (EPCCT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3133-3133
Author(s):  
Rozana Abdul Rahman ◽  
Neethu Billy Graham Mariam ◽  
Hitesh Mistry ◽  
Sreeja Aruketty ◽  
Matt Church ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Rates ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Sustained Response ◽  
Phase Ii Trials ◽  
Significant Difference

3133 Background: The primary objective of EPCCT (phase I and non-randomised phase II trials) is to determine the safety and tolerability of new therapeutic agents. Response rates (RR) in these trials have typically been reported at around 10-15%. Increasingly RR and survival outcomes are now investigated in EPCCT as primary or secondary objectives. Methods: Retrospective data analysis was performed on patients (pts) enrolled onto an EPCCT between January 2018 and December 2019 at The Christie NHS Foundation Trust, UK. Data on demographics, prior systemic treatment, sites of disease, performance status, comorbidities, types of therapy, RR, progression free survival (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable models. Objective response rate (ORR) was defined as the proportion of pts with complete response (CR) and partial response (PR). Duration of response (DOR) was from initial response to progressive disease (PD). Disease control rate (DCR) was defined as CR+PR+ stable disease (SD). Results: A total of 247 pts were treated across 46 EPCCTs. Median age 61 years; 57% female. Sixty-six percent of pts had ≥2 lines of treatment and the majority were ECOG PS 0/1 (98%). Eighty-one percent of pts had ≥2 sites of metastatic disease, and 13 major tumour types were included. Monotherapy trials (159 pts) were predominantly targeted therapies (TT; 60%), or immunotherapies (IO; 20%). Combination therapy trials (88 pts) were TT-based (68%) or IO-based (32%). Data for RR analyses was available for 231 pts. ORR across all trials was 15% (CR 2%) and DCR was 63%. The median DOR was 8.3 months (mos) (95% CI: 7.0 – 9.7) with 28% of pts responding for >6 mos and 7% for >12 mos. ORR in pooled IO treated pts was 27%, DCR was 65% with sustained response >6 mos seen in 37% of these pts. ORR in pooled TT treated pts was 9.4%, DCR was 60% and sustained response > 6 mos seen in 25% of pts. ORR for IO v TT treated pts was significantly different, p=0.007 (pearson chi square), but no significant difference was seen for DCR. Median PFS for all patients was 5.0 mos (95% CI: 4.1 – 6.0) and OS was 10.4 mos (95% CI: 8.4 – 13.0). OS for those with a PR is not reached (HR for PR v PD, 0.006 (95% CI: 0.002 – 0.18). Pts with SD appear to have significantly better OS compared to those with PD (14.6 v 4.2 mos, HR 0.2 (95% CI: 0.1 – 0.3). Multivariable Cox proportional hazards analysis for OS was significant for male gender (HR 1.9, p=0.002), presence of liver metastasis (HR 2.0, p=0.001), low Hb (HR 0.8, p=0.03) and log (LDH) (HR 1.9, p<0.001). Conclusions: Two-thirds of pts enrolled on EPCCTs benefitted in terms of DCR with significant OS improvement in those with PR and SD. Higher ORR were seen in pts receiving IO-based treatments however DCR was similar in IO and TT pts. Gender, presence of liver metastases, Hb count and LDH level contributed significantly to survival differences.

Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5599-TPS5599
Author(s):  
Rebecca Christian Arend ◽  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Jonathan A. Ledermann ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Recist 1.1 ◽  
Platinum Resistant ◽  
Phase Iii Study

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Joyce O'Shaughnessy ◽  
Kevin Punie ◽  
Mafalda Oliveira ◽  
Filipa Lynce ◽  
Sara M. Tolaney ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Antibody Drug Conjugate ◽  
Phase 3 ◽  
Chemotherapy Agent ◽  
Recist 1.1 ◽  
Duration Of Response ◽  
Grade 3

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients With Metastatic Renal Cell Carcinoma

2017 ◽  
Vol 35 (16) ◽  
pp. 1764-1769 ◽  
Author(s):  
Moshe C. Ornstein ◽  
Laura S. Wood ◽  
Paul Elson ◽  
Kimberly D. Allman ◽  
Jennifer Beach ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Primary Objective ◽  
Intermittent Therapy

Purpose Sunitinib is a standard initial therapy in metastatic renal cell carcinoma (mRCC), but chronic dosing requires balancing toxicity with clinical benefit. The feasibility and clinical outcome with intermittent sunitinib dosing in patients with mRCC was explored. Patients and Methods Patients with treatment-naïve, clear cell mRCC were treated with four cycles of sunitinib (50 mg once per day, 4 weeks of receiving treatment followed by 2 weeks of no treatment). Patients with a ≥ 10% reduction in tumor burden (TB) after four cycles had sunitinib held, with restaging scans performed every two cycles. Sunitinib was reinitiated for two cycles in those patients with an increase in TB by ≥ 10%, and again held with ≥ 10% TB reduction. This intermittent sunitinib dosing continued until Response Evaluation Criteria in Solid Tumors-defined disease progression while receiving sunitinib, or unacceptable toxicity occurred. The primary objective was feasibility, defined as the proportion of eligible patients who underwent intermittent therapy. Results Of 37 patients enrolled, 20 were eligible for intermittent therapy and all patients (100%) entered the intermittent phase. Patients were not eligible for intermittent sunitinib because of progressive disease (n = 13), toxicity (n = 1), or consent withdrawal (n = 3) before the end of cycle 4. The objective response rate was 46% after the first four cycles of therapy. The median increase in TB during the periods off sunitinib was 1.6 cm (range, −2.9 to 3.4 cm) compared with the TB immediately before stopping sunitinib. Most patients exhibited a stable sawtooth pattern of TB reduction while receiving sunitinib and TB increase while not receiving sunitinib. Median progression-free survival to date is 22.4 months (95% CI, 5.4 to 37.6 months) and median overall survival is 34.8 months (95% CI, 14.8 months to not applicable). Conclusion Periodic extended sunitinib treatment breaks are feasible and clinical efficacy does not seem to be compromised.

Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: A randomized, double-blind phase III trial (ZEST)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8009-8009
Author(s):  
R. B. Natale ◽  
S. Thongprasert ◽  
F. A. Greco ◽  
M. Thomas ◽  
C. M. Tsai ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind ◽  
Equivalent Efficacy ◽  
Secondary Endpoints ◽  
Previously Treated ◽  
Grade 3 ◽  
To Receive

8009 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. This phase III study compared the efficacy of vandetanib vs erlotinib in patients (pts) with advanced, previously treated NSCLC. Methods: Eligible pts (stage IIIB/IV NSCLC, PS 0–2, 1–2 prior chemotherapies; all histologies permitted) were randomized 1:1 to receive vandetanib 300 mg/day or erlotinib 150 mg/day until progression/toxicity. The primary objective was to show superiority in progression-free survival (PFS) for vandetanib vs erlotinib. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to deterioration of symptoms (TDS; EORTC QoL Questionnaire) and safety. Results: Between Oct 06-Nov 07, 1240 pts (mean age 61 yrs; 38% female; 22% squamous) were randomized to receive vandetanib (n=623) or erlotinib (n=617). Baseline characteristics were similar in both arms. Median duration of follow-up was 14 months, with 88% pts progressed and 67% dead. There was no difference in PFS for pts treated with vandetanib vs erlotinib (hazard ratio [HR] 0.98, 95.22% CI 0.87–1.10; P=0.721), and no difference in the secondary endpoints of OS (HR 1.01, 95.08% CI 0.89–1.16; P=0.830), ORR (both 12%) and TDS (pain: HR 0.92, P=0.289; dyspnea: HR 1.07, P=0.407; cough: HR 0.94, P=0.455). A preplanned non-inferiority analysis for PFS and OS demonstrated equivalent efficacy for vandetanib and erlotinib. The adverse events (AEs) observed for vandetanib were generally consistent with previous NSCLC studies with vandetanib 300 mg. There was a higher incidence of some AEs (any grade) with vandetanib vs erlotinib, including diarrhea (50% vs 38%) and hypertension (16% vs 2%); rash was more frequent with erlotinib (38% vs 28%). The overall incidence of CTCAE grade ≥3 AEs was also higher with vandetanib (50% vs 40%). The incidence of protocol-defined QTc prolongation in the vandetanib arm was 5%. Conclusions: The study did not meet its primary objective of demonstrating PFS prolongation with vandetanib vs erlotinib in pts with previously treated advanced NSCLC. However, vandetanib and erlotinib showed equivalent efficacy for PFS and OS in a preplanned non-inferiority analysis. [Table: see text]

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