Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): Primary analysis of IMvigor210 cohort 1.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA4500-LBA4500 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Matt D. Galsky ◽  
Yohann Loriot ◽  
Nancy Ann Dawson ◽  
Andrea Necchi ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Attractive Alternative ◽  
Primary Analysis ◽  
Meaningful Activity ◽  
Immune Mediated ◽  
Metastatic Setting ◽  
Independent Review ◽  
Metastatic Urothelial Carcinoma ◽  
Clinical Trial Information

LBA4500 Background: Cisplatin-based chemo is a standard 1L treatment (tx) for mUC and the only tx that prolongs OS; however, age or comorbidities render many pts ineligible, and 30-50% receive no tx. Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts. Methods: Pts were chemo naive in the metastatic setting and cisplatin ineligible (renal [GFR > 30 but < 60 mL/min]/hearing impairment, ≥ G2 peripheral neuropathy [PN] or ≥ ECOG PS2). Atezo 1200 mg was given IV q3w until PD (RECIST v1.1). Centrally assessed PD-L1 on tumor infiltrating immune cells (IC; SP142 IHC assay) was scored IC2/3, 1 or 0. The primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1 (central independent review facility) using a data cutoff of Sep 14, 2015. Results: 119 efficacy/safety-evaluable pts of any PD-L1 IC had a median age of 73 y: 21% ≥ 80 y. 18% had prior systemic tx (21% [neo]adjuvant); 10% had radiotherapy. 66% had visceral mets. 71% had CrCl < 60 mL/min; 13% had hearing loss ≥ 25 dB; 6% had prior PN ≥ G2; 20% had ECOG PS2. ORR was 19% (95% CI 13-28; 5% CR), and responses occurred in all IC subgroups (Table; includes DCR/PFS/OS) and in pts with poor prognostic factors. 22/23 responses were ongoing with mDOR not reached. Median follow-up was 8.5 mo (range 0.2-14.3); median tx duration was 15 wk. Atezo was generally well tolerated. Tx-related all-G and G3-4 AEs were seen in 64% and 12% of pts, respectively. Related all-G AEs ≥ 10% included fatigue, pruritus, diarrhea. 1 G5 related AE occurred (sepsis). 3% had a G3-4 immune-mediated AE. Conclusions: Atezo has clinically meaningful activity in 1L cisplatin-ineligible mUC pts, and preliminary OS is encouraging. The durable nature of response and favorable AE profile makes this an attractive alternative to chemo. NCT02108652. Clinical trial information: NCT02108652. [Table: see text]

IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Jean H. Hoffman-Censits ◽  
Petros Grivas ◽  
Michiel Simon Van Der Heijden ◽  
Robert Dreicer ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Antitumor Immunity ◽  
Immune Cell ◽  
Locally Advanced ◽  
Primary Endpoints ◽  
Immune Mediated ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Clinical Trial Information

355 Background: The ORR and survival of mUC patients (pts) who progress after platinum-based chemotherapy (pctx) are poor. Atezolizumab (atezo) reinvigorates antitumor immunity by targeting PD-L1 and has shown promising Ph 1 activity in mUC. Methods: IMvigor 210 cohort 2 (NCT02108652) enrolled 316 mUC pts who progressed during or following pctx. Pts received atezo at 1200 mg IV q3w until loss of clinical benefit. The SP142 IHC assay centrally assessed PD-L1 expression. Pts/investigators were blinded to PD-L1 status. Co-primary endpoints were confirmed ORR by RECIST v1.1 per central review (IRF) and modified (m) RECIST per investigator, which were met if null hypothesis (ORR = 10%) was rejected (α = 5%). ORR endpoints were stratified by PD-L1 tumor-infiltrating immune cell (IC) status: IC2/3, IC1/2/3, all comers. Results: Efficacy/safety-evaluable pts (N = 311) had a median age of 66 y, CrCl < 60 mL/min (35%) and ≥ 2 prior regimens for mUC (40%). Many had poor prognostic factors (Table). At 5/5/15 data cutoff (follow up ≥ 24 w), 43/47 responding pts had ongoing responses. Both IRF (Table) and mRECIST ORR correlated with IC status. Durable responses were seen including poor prognostic subgroups (Table). mDOR was not reached in any PD-L1 or prognostic subgroup. mPFS was 2.1 mo in all PD-L1 subgroups. Median treatment duration was 12 w (range 0-46). Treatment-related AEs (most commonly fatigue) occurred in 66% of pts (all Grade); 15% had G3-4 related AE and 4% had G3-4 immune-mediated AE. 27% of AEs led to dose interruption and 3% led to withdrawal. No renal toxicity was seen. Conclusions: IMvigor 210, the first Ph 2 study targeting PD-L1/PD-1 in mUC, demonstrated significantly improved ORR vs historic controls. Responses were durable and associated with higher PD-L1 IC expression; poor prognostic factors did not preclude response. Atezo was well tolerated, and a randomized Ph 3 study vs ctx is ongoing (IMvigor 211; NCT02302807). Clinical trial information: NCT02108652. [Table: see text]

An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9013-9013 ◽  
Author(s):  
Axel Hauschild ◽  
Jean Jacques Grob ◽  
Lev V. Demidov ◽  
Thomas Jouary ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Phase Iii ◽  
Primary Analysis ◽  
Free Survival ◽  
Independent Review ◽  
Clinical Trial Information

9013 Background: Dabrafenib is a selective BRAF inhibitor with demonstrated efficacy in BRAF V600E-positive mutation in MM. The primary analysis of BREAK-3 (NCT01227889) compared progression-free survival (PFS) in patients (pts) with BRAF V600E-positive mutation MM treated with dabrafenib or DTIC. Methods: Median PFS for dabrafenib of 5.1 months (mo) and study methods were previously described (Hauschild A, et al. Lancet. 2012,380:358–365). Independent review ended at the primary analysis. PFS was updated in Jun 2012 at median follow-up of 10.5 mo for dabrafenib (67% of PFS events), and 9.9 mo for DTIC. Median overall survival (OS) was not reached, so another analysis of OS and safety was performed with data as of Dec 2012, at which time the median follow-up was 15.2 (dabrafenib) and 12.7 (DTIC) mo. PFS of subjects who crossed over was also evaluated at that time. Results: PFS hazard ratio was 0.37 [95% CI; 0.23, 0.57]; median PFS was 6.9 mo dabrafenib and 2.7 mo DTIC. In Dec 2012, 36/63 DTIC pts crossed over; median PFS was 4.3 [95% CI; 4.1, 6.1] mos. OS is presented in the Table.The four most common adverse events (AE) on the dabrafenib arm were hyperkeratosis (39%), headache (35%), arthralgia (35%), and pyrexia (32%). Serious AEs ≥ 5% on the dabrafenib arm included cutaneous squamous cell carcinoma/keratoacanthoma (10%) and pyrexia (5%). Conclusions: Longer follow-up confirms the benefits of dabrafenib on PFS and response rate. Median OS in the dabrafenib arm was over 18 mo and over 15 mo in the DTIC arm. OS results are confounded by crossover of DTIC pts to dabrafenib and likely by subsequent therapy after progression. The effects of subsequent therapy results will be investigated. The safety profile had no significant changes. Clinical trial information: NCT01227889. [Table: see text]

Durability of complete response (CR) with atezolizumab (atezo) in locally advanced/metastatic urothelial carcinoma (mUC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4527-4527
Author(s):  
Yohann Loriot ◽  
Arjun Vasant Balar ◽  
Robert Dreicer ◽  
Jean H. Hoffman-Censits ◽  
Jose Luis Perez-Gracia ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Complete Response ◽  
First Response ◽  
Long Term Follow Up ◽  
Metastatic Urothelial Carcinoma ◽  
Post Hoc ◽  
Clinical Trial Information ◽  
Disposition Time

4527 Background: Atezo (anti–PD-L1) has been shown to elicit CRs in a number of mUC patients (pts) in clinical trials. We sought to describe the kinetics, durability and outcomes associated with these CRs in Ph I (PCD) and II (IMvigor210) atezo studies, each with long-term follow-up. Methods: In PCD (pre-treated mUC) and IMvigor210 (Cohort 1, cisplatin-ineligible untreated mUC; Cohort 2, platinum-treated mUC), pts received atezo per protocol (Petrylak JAMA Oncol 2018; Balar Lancet 2017; Rosenberg Lancet 2016). This post hoc analysis descriptively assessed pt disposition, time to and duration of RECIST 1.1 response and overall survival in pts with CR. Results: CR rates were 13%, 8% and 7% in PCD, IMvigor210 Cohort 1 and Cohort 2, respectively. First response was PR in most pts with CR. Median CR duration was > 3 y in PCD, not estimable (NE) in IMvigor210 Cohort 1 and > 2 y in Cohort 2 (Table). At data cutoff, all but 2, 0 and 1 pts were alive, respectively; across studies, ≥ 40% of pts with CR were on treatment. CR pts had a first response (PR/CR) by a median of 3.5 cycles. Further pt characteristics and survival outcomes will be reported. Conclusions: Across Ph I/II atezo mUC studies, CRs appeared durable (median duration > 2 y) despite small pt numbers. Most pts with CR were alive, with responses ongoing after long-term follow-up (median follow-up > 30 mo). Clinical trial information: NCT01375842, NCT02951767, NCT02108652. [Table: see text]

Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001.

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. LBA9015-LBA9015 ◽  
Author(s):  
Edward B. Garon ◽  
Matthew David Hellmann ◽  
Enric Carcereny Costa ◽  
Natasha B. Leighl ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Locally Advanced ◽  
Metastatic Nsclc ◽  
Immune Mediated ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Phase 1B ◽  
Clinical Trial Information

LBA9015 Background: Pembrolizumab (pembro) monotherapy has demonstrated durable antitumor activity in advanced PD-L1–expressing NSCLC. We present 5-y OS for patients (pts) enrolled in the phase 1b KEYNOTE-001 study (NCT01295827), the first trial evaluating pembro in advanced NSCLC. These data provide the longest efficacy/safety follow-up for NSCLC pts treated with pembro. Methods: Pts had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumor sample for PD-L1 evaluation by IHC using the 22C3 antibody. Pts received pembro 2 mg/kg Q3W or 10 mg/kg Q2W or Q3W. The primary efficacy endpoint was ORR. OS was a secondary endpoint. Results: 550 pts were enrolled (treatment-naive, n=101; previously treated, n=449). As of November 5, 2018 (data cutoff), median (range) follow-up was 60.6 (51.8–77.9) mo; 82% (n=450/550) had died. Estimated 5-y OS rates were 23.2% for treatment-naive pts and 15.5% for previously treated pts (Table). ORR (by investigator per irRC) was 42% (95% CI, 32–52) for treatment-naive pts and 23% (95% CI, 19–27) for previously treated pts. Median (range) DOR was 16.8 (2.1+ to 55.7+) mo and 38.9 (1.0+ to 71.8+) mo, respectively. Immune-mediated AEs had occurred in 17% of pts at 5 y, similar to the incidence reported at 3-y follow-up. Additional results, including outcomes in key subgroups and detailed safety follow-up data, will be presented. Conclusions: In KEYNOTE-001, 5-y OS rate was 23.2% in treatment-naive pts and 15.5% in previously treated pts with advanced NSCLC treated with pembro, compared to a historical rate of ~5% (per SEER 2008–2014), prior to the introduction of anti–PD-1 therapy. 5-y OS rate was at least 25% in pts with PD-L1 TPS ≥50% in both pt populations in KEYNOTE-001. Clinical trial information: NCT01295827. [Table: see text]

Efficacy and safety of the hedgehog pathway inhibitor vismodegib in patients with advanced basal cell carcinoma (BCC): ERIVANCE BCC study update.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8579-8579 ◽  
Author(s):  
Aleksandar Sekulic ◽  
Michael R Migden ◽  
Anthony E Oro ◽  
Karl D Lewis ◽  
John D Hainsworth ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
Primary Analysis ◽  
Molecule Inhibitor ◽  
The Us ◽  
Independent Review ◽  
One Year ◽  
Weight Decrease

8579 Background: The ERIVANCE BCC study is the pivotal trial of vismodegib (GDC-0449), a first-in-class small-molecule inhibitor of Hedgehog signaling, for treatment of locally advanced (laBCC) and metastatic BCC (mBCC), for whom there are no other effective therapy options. The study met the primary endpoint of overall response rate by independent review (Sekulic, Melanoma Res 2011). Here we report a 6-mo update of investigator-assessed (I-A) efficacy and safety endpoints as of May 26, 2011. Methods: This multicenter, international, nonrandomized 2-cohort study enrolled patients (pts) with laBCC (deemed inoperable or for whom surgery would be significantly disfiguring), and mBCC pts with RECIST-measurable disease. Pts received 150 mg oral vismodegib daily. Results: 104 pts (71 laBCC/33 mBCC) enrolled at 31 sites in the US, Europe, and Australia. I-A efficacy endpoints are shown in the table. One-year survival rate was 77.3% (95% CI 62.48–92.09%) for mBCC and 93.1% (95% CI 86.49–99.63%) for laBCC. Adverse events (AEs) in >30% of pts were muscle spasms, alopecia, dysgeusia, weight decrease, fatigue, nausea, and amenorrhea (33.3%; 2/6 pts). Serious AEs were reported in 32 pts (31%). No additional fatal AEs were reported since the prior data cut (n=7, 7%; none considered related to vismodegib). Conclusions: This 6-mo update of I-A efficacy and safety endpoints from the ERIVANCE BCC study supports the significant clinical benefit of vismodegib in both laBCC and mBCC reported at the primary analysis. Median DOR and PFS increased numerically with follow-up. The AE profile was consistent with the prior data cut. These results further support the efficacy of vismodegib for treatment of advanced BCC. [Table: see text]

Long-term follow-up of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck (SCCHN).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6020-6020
Author(s):  
Byoung Chul Cho ◽  
Amaury Daste ◽  
Alain Ravaud ◽  
Sébastien Salas ◽  
Nicolas Isambert ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Safety Profile ◽  
Objective Response ◽  
Locally Advanced ◽  
Clinical Activity ◽  
Metastatic Setting ◽  
Heavily Pretreated ◽  
Bifunctional Fusion Protein

6020 Background: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. A previous report of an expansion cohort from a phase 1 study (NCT02517398) suggested that bintrafusp alfa had a manageable safety profile and early signs of clinical activity in patients with heavily pretreated, advanced SCCHN after a median follow-up of 86.4 weeks. Here we report long-term efficacy and safety for this cohort. Methods: Patients with advanced SCCHN that progressed/recurred after platinum therapy in the recurrent/metastatic setting, or < 6 months after platinum therapy in the locally advanced setting, received bintrafusp alfa 1200 mg every 2 weeks until confirmed progressive disease, unacceptable toxicity, or trial withdrawal. The primary endpoint was confirmed best overall response assessed per RECIST 1.1 assessed by independent review committee (IRC); safety was a secondary endpoint. Results: As of May 15, 2020, 32 patients had received bintrafusp alfa for a median of 2.8 months (range, 0.5-29.9 months), no patient remained on treatment, and median follow-up to data cutoff was 41.7 months (range, 39.8-43.5 months). The objective response rate (ORR; 13%) was unchanged since the previous report; median duration of response (DOR) was increased at 21.4 months (95% CI, 5.5 months to not reached [NR]). While the clinical activity of bintrafusp alfa may be improved in patients with HPV-positive tumors (Table), outcomes were generally similar between PD-L1 subgroups (≥1% vs < 1% tumor cells). The overall safety profile was consistent with the previous report for this cohort, without grade 4 nor 5 treatment-related adverse events (TRAEs); no new TRAEs of grade 3 or that led to discontinuation of bintrafusp alfa were reported. Conclusions: With a median follow-up of over 3 years in patients with heavily pretreated advanced SCCHN, bintrafusp alfa showed sustained clinical activity and 3-year OS of 24.0%, which compares favorably to historical data. Clinical activity appeared to be greater in patients with HPV-positive tumors than those with HPV-negative tumors. The safety profile was manageable and consistent with earlier analysis. Further investigation of bintrafusp alfa in SCCHN and other HPV-associated cancers is ongoing. Clinical trial information: NCT02517398. [Table: see text]

Preoperative uracil/tegafur and concomitant radiotherapy in locally advanced rectal (LAR) cancer: Updated results with a median follow-up of 5 years and analysis of prognostic factors (PF)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3573-3573 ◽  
Author(s):  
C. Fernandez-Martos ◽  
I. Romero ◽  
J. Aparicio ◽  
C. Bosch ◽  
R. Girones ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Residual Disease ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Information ◽  
Risk Groups ◽  
Attractive Alternative

3573 Background: Preop chemoradiotherapy (CRT) with CI 5-FU is a standard of care for LAR cancer. Oral fluoropyrimidines, an attractive alternative to intravenous 5-FU, are perceived by patients as more convenient. Methods: We performed a phase II study in patients with potentially resectable tumors, localized in middle or distal rectum, ultrasonographically staged as T3 or T4 or N+ who were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Pts underwent surgery 5 to 6 weeks later followed by four cycles of 5-FU/LV (Mayo Clinic Scheme). Early end points of efficacy (pCR, downstaging, sphincter preserving surgery) and toxicity have already been reported (JCO 2004;22:3016). We now present data on secondary objectives (RFS, DFS and OS) and univariate and multivariate analysis of clinical and pathological PF. Results: 94 patients were included and complete information on 88 (94%) is availablewith a median follow-up of 5 years (60.4 months). Actuarial Kaplan-Meier DFS, RFS and OS are 61%, 66%, and 70 %. Patterns of failure are 7% pelvic and 25% distant. Univariate analysis results are shown in the table . Survival rate was also higher among patients with no or few residual disease after CRT but did not reach statistical significance. In Cox multivariate analysis both ypT and ypN are independent PF for DFS and RFS but only ypT is an independent PF for OS. Conclusions: This approach with preop UFT/RT reproduces the results that have been accomplished with 5-FU. ypT and ypN could be helpful to identify different risk groups and to select adjuvant treatments. [Table: see text] No significant financial relationships to disclose.

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma (aBCC): 18-month update of the pivotal ERIVANCE BCC study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9037-9037 ◽  
Author(s):  
Aleksandar Sekulic ◽  
Michael R. Migden ◽  
Nicole Basset-Seguin ◽  
Claus Garbe ◽  
Anja Gesierich ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Safety Data ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Hedgehog Pathway ◽  
Primary Analysis ◽  
Weight Decrease

9037 Background: Therapies for aBCC, which includes metastatic (m) and locally advanced (la) BCC, are limited. Abnormal Hedgehog pathway signaling is a key driver in BCC pathogenesis. Primary analysis of the pivotal ERIVANCE BCC trial of vismodegib, an oral hedgehog pathway inhibitor (HPI), demonstrated an objective response rate (ORR) of 30% and 43%, in mBCC and laBCC patients, respectively, with a median duration of response (DOR) of 7.6 months. We present safety and investigator (INV) assessed efficacy results 18 months (29 May 2012) after primary analysis (26 Nov 2010). Methods: Multicenter, international, nonrandomized study in patients (N=104) with radiographically measurable mBCC or laBCC (surgery inappropriate due to multiple recurrence, or substantial morbidity or deformity anticipated) receiving 150 mg oral vismodegib daily until disease progression or intolerable toxicity. Key secondary endpoints included INV-assessed ORR, progression-free survival (PFS), DOR, overall survival (OS), and safety. Results: At data cutoff, 21 patients continued to undergo protocol-specified assessments and 56 patients were in survival follow-up. The median dose intensity was comparable with primary analysis. ORR was 48.5%, mBCC; 60.3%, laBCC, comparable with primary analysis. However, median DOR improved (mBCC=14.7; laBCC=20.3 months). The median OS for mBCC was 30.9 months but not estimable in laBCC. Adverse events remained consistent, with muscle spasm, alopecia, dysgeusia, weight decrease, and fatigue most frequently reported. Eleven more deaths were reported in the update period after primary analysis; these occurred in survival follow-up and were not drug-related. Conclusions: Vismodegib is the first FDA-approved HPI; thus, long-term efficacy and safety data are particularly relevant. 18-month update data confirmed prolonged responses and consistent safety in vismodegib-treated aBCC patients. Clinical trial information: NCT00833417.

FOLFIRINOX and gemcitabine/nab-paclitaxel efficacy in the treatment of locally advanced unresectable pancreatic adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 399-399
Author(s):  
Filip Bednar ◽  
Lee Mayer Ocuin ◽  
Jennifer Steve ◽  
Mazen S Zenati ◽  
Sharon Winters ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Therapy Group ◽  
Locally Advanced ◽  
Group 4 ◽  
Metastatic Setting ◽  
Drug Regimens ◽  
Group 3 ◽  
Group 2 ◽  
Line Of Therapy

399 Background: Locally advanced (LA) unresectable pancreatic adenocarcinoma (PDA) historically portends a poor prognosis with a median OS of 9-11 months. Recently, two multi-drug regimens – FOLFIRINOX and gemcitabine/nab-paclitaxel – have proven effective in the metastatic setting. We hypothesized that use of these regimens in the LA setting may improve survival. Methods: A retrospective review of a single institution’s cancer registry of all consecutive LA (unresectable) PDA patients between 2010 and 2014 was performed. LA status was verified by review of the triphasic, pancreas protocol CT scan at diagnosis using the 2015 NCCN criteria for resectability. Patients were divided into 4 groups: Group 1 = no therapy, Group 2 = “old” gemcitabine or 5-FU-based chemotherapy (CTX), Group 3 = “new” CTX (FOLFIRINOX and/or Gem/nab-paclitaxel), and Group 4 = resection after downstaging. Demographic, tumor related variables, and treatment outcomes were analyzed. Results: LA disease was verified in 107 consecutive patients. Median age was 69 years (range 36-92) and 50.5% were male. Median follow-up was 13.2 months (range 0.6-60.4). Median OS for Groups 1 (n=15), 2 (n=24), 3 (n=49), 4 (n=19) was 1.4, 11, 17.3, and 32 months respectively (p<0.001). On Cox multivariate regression (adjusted for age, sex, anatomic variables, and CA19-9 level at diagnosis), radiation (HR 0.44, p=0.003), older CTX (HR 0.16, p=0.007), newer CTX (HR 0.10, p=0.001), use of 2 or more lines of CTX (HR 0.16, p=0.022), CA19-9 decrease by >50% with any line of therapy (HR 0.31, p<0.001), and surgery (HR 0.28, p=0.002) were all significant predictors of OS in this cohort. On multivariate analysis between groups 2 and 3, newer CTX compared to older CTX (HR 0.490, p=0.02) and radiation (HR 0.510, p=0.015) provided an OS benefit. Conclusions: Compared to older CTX regimens, FOLFIRINOX and Gemcitabine/nab-paclitaxel improve survival in verified LA PDA patients. For the subset that ultimately undergoes resection, survival outcomes rival those of historically published resectable cohorts.

Atezolizumab (atezo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Safety analysis from an expanded access study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4532-4532
Author(s):  
Joaquim Bellmunt ◽  
Sumanta K. Pal ◽  
Hanzhe Zheng ◽  
Darren Tayama ◽  
Dannis Chang ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Clinical Activity ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Fda Approval ◽  
The Us ◽  
Metastatic Urothelial Carcinoma ◽  
Access Program ◽  
Clinical Trial Information ◽  
Efficacy Population

4532 Background: A majority of mUC pts progress on standard platinum-based chemo regimens. Atezo (anti–PD-L1) was approved in the US for mUC in the post-platinum setting. Here we report the preliminary safety results from an expanded access program conducted to grant access to atezo, prior to commercial availability, to a broader range of mUC pts than are typically eligible for Phase I-III studies. Methods: From Nov 2015-Aug 2016, this study (NCT02589717) enrolled mUC pts who progressed during or following platinum. Atezo was given 1200 mg IV q3w, and pts could be treated post RECIST v1.1 PD until lack of clinical benefit (per investigator). Safety and clinical activity were key endpoints. PD-L1 expression on immune cells (IC) was assessed with the VENTANA SP142 IHC assay on the first 73 pts prior to protocol amendment omitting this requirement. This study was ended early following FDA approval of atezo. Results: 218 pts were enrolled at 36 sites in the US, with 214 treated pts comprising the safety/efficacy population (Table). Median treatment duration was 9 wks (range 3-26), corresponding to a median of 3 doses of atezo (range 1-8). Overall, 89% of pts had an AE. Treatment-related AEs (TRAEs) occurred in 46% (any Gr) and 7% (Gr3-4) of pts; 2 treatment-related Gr 5 AEs were seen (ileus; acute respiratory failure). TRAEs ≥ 5% were fatigue, decreased appetite and anemia. TRAEs leading to dose interruption or discontinuation occurred in 11% and 6% of pts, respectively. Investigator-assessed RECIST v1.1 ORR was 15% (95% CI: 9, 23), and disease control rate (ORR + SD) was 49% (95% CI: 40, 59). Additional clinical data will be reported. Conclusions: In this expanded access study, atezo was administered to > 200 mUC pts. Overall, atezo was safe and tolerable, supporting its use in a wider platinum-based population. Clinical trial information: NCT02589717. [Table: see text]

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