Ziv-aflibercept (A) combined to FOLFIRI as first line treatment for metastatic colorectal cancer (mCRC): Interim safety and efficacy results of the phase II PULSAR trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 737-737 ◽  
Author(s):  
Antoine Adenis ◽  
Francois Ghiringhelli ◽  
Jean Luc Raoul ◽  
Emmanuelle Tresch ◽  
Anne Thirot-Bidault ◽  
...  
Keyword(s):  
Median Number ◽  
Colon Perforation ◽  
Target Sample Size ◽  
Contrast Enhanced ◽  
Previously Treated ◽  
Intent To Treat ◽  
Line Setting ◽  
Dose Modifications ◽  
Ecog Ps

737 Background: A is approved in combination with FOLFIRI (A-FOLFIRI) for the treatment of mCRC patients (pts) previously treated with oxaliplatin. PULSAR trial (NCT02173990) aims to measure the activity A-FOLFIRI as 1st-line mCRC treatment. Key secondary objectives are safety, as well as circulating biomarkers and dynamic contrast-enhanced ultrasound measurements as PFS prognosticators. We present here interim analysis of safety and activity. Methods: Pts received A (4 mg/kg I.V.) every 2 weeks in combination with FOLFIRI (Irinotecan: 180 mg/m2, leucovorin: 200 mg/m2, Bolus FU: 400 mg/m2, infusional FU: 2400 mg/m2 over 46hrs). The primary endpoint is 10-month [m] PFS (RECIST 1.1). The target sample size is 72 pts for the following assumptions: P0 = 0.40, P1 = 0.55, α = β = 0.1. Results: Among the first 30 recruited mCRC pts with unresectable metastases (mets), 29 received at least 1 cycle of A-FOLFIRI. 30, 23, and 28 pts were evaluable for survival (intent-to-treat), tumor response, and safety, respectively. Median age was 61.5 (45-82), 70% pts were men. ECOG PS was 0, 1, and 2, in 47%, 43%, and 10% of the pts. 6/30 pts received previous adjuvant chemotherapy. 22/30 pts presented with synchronous mets. 26/30 pts presented with liver mets. Median treatment duration was 6.3m (0.5-24.3) and pts (n = 29) received a median number of 10 cycles (1-37) of A and of 11 cycles (1-43) of FOLFIRI. Median follow-up was 7.2m (1.6-23.9). The 10-m PFS was 59.9% [95%-CI: 37.5-76.5]. Median PFS was 12.9m (95% CI: 6.1-…). 12-m OS rate was 73.7% (95% CI: 48.3-87.9). 5 pts died from PD, and 1 from treatment-related toxicity (colon perforation). 27/28 pts presented at least one severe Adverse Event (AE). Most frequent severe AE (related or not) were hypertension (43%), neutropenia (29%), diarrhea (18%), alkaline phosphatase increase (18%), fatigue (18%), GGT increase (14%), and weight loss (14%). Conclusions: A-FOLFIRI seems promising in 1st line setting mCRC, with respect to PFS. Due to high rates of severe AEs, dose modifications have to be proceeded in a coming protocol amendment. Funded by Sanofi. Clinical trial information: NCT02173990.

Pembrolizumab as first-line therapy in patients with unresectable cutaneous squamous cell carcinoma (cSCC): Phase 2 results from CARSKIN.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9547-9547 ◽  
Author(s):  
Eve Maubec ◽  
Marouane Boubaya ◽  
Peter Petrow ◽  
Nicole Basset-Seguin ◽  
Jean Jacques Grob ◽  
...  
Keyword(s):  
Tumor Response ◽  
Blocking Agent ◽  
Median Number ◽  
First Line ◽  
Stage Design ◽  
First Line Therapy ◽  
Independent Review ◽  
Line Setting ◽  
Ecog Ps

9547 Background: Cemiplimab, a PD-1-axis blocking agent, has recently been approved for unresectable cSCCs. We report results of the CARSKIN study evaluating pembrolizumab in the first-line setting. Methods: Chemotherapy naive patients (pts) with unresectable cSCCs, either locally or regionally advanced or metastatic, and ECOG PS ≤1 were accrued to this multi-institutional phase II trial to assess tumor response rate (RR) and safety of pembrolizumab administered IV (200 mg Q3W) for a period up to 24 months (mo). Baseline PD-L1 expression was centrally assessed on tumor. The primary endpoint was the RR at 15 weeks (wks) per RECIST v1.1 (independent review). A Simon two-stage design was used. Results: From 03/2017 to 01/2018, 39 pts (79% males, median age 79 years) were enrolled. Disease was local (18%), regional (62%) or metastatic (21%); 38% of pts were PS 0. The median number of infusions was 8. The median follow-up was 10.2 mo; 15 pts are still on pembrolizumab. Thirty-four pts were evaluable for tumor response, and 39 for toxicity. The RR at 15 wks was 38.5 % (95% CI: 24–55%) in the ITT population corresponding to 2 CR and 13 PR. The best responses were 3 CR and 12 PR. The DCR was 51% (20/39 including 5 SD) at 15 wks. The median PFS was 8.4 mo and the median OS was not reached. No responder has progressed to date including 2 pts who discontinued pembrolizumab for 6 to 12 mo. Treatment-related AEs (TRAEs) occurred in 67% of pts, including 8% with severe TRAEs (1 gr 3 cholestasis, 1 gr 3 colitis and 1 death due to recurrence of a non-related head and neck cancer) and 10% who discontinued because of a TRAE. Centrally assessed baseline PD-L1 expression was positive in 77% of patients (1% tumor staining threshold), but it failed to predict response at 15 wks with a median PD-L1 expression of 10% in responders and non-responders at 15 wks (P = .55). Conclusions: In this series of 39 elderly pts with unresectable cSCCs, the safety profile was consistent with previous pembrolizumab studies. First-line pembrolizumab provided robust antitumor activity regardless of PD-L1 expression levels. Clinical trial information: NCT02883556.

Biweekly paclitaxel as second-line treatment in advanced non-small cell lung-cancer (NSCLC). A phase II study of the Lung Cancer Galician Group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18120-18120
Author(s):  
S. Vazquez-Estevez ◽  
J. Fírvida ◽  
G. Huidobro ◽  
L. León ◽  
M. Lázaro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Nsclc ◽  
Dose Intensity ◽  
Tumor Stage ◽  
Median Number ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Intent To Treat ◽  
Ecog Ps ◽  
Grade Iii

18120 Background: Paclitaxel is an active drug for NSCLC. Our purpose was to evaluate the efficacy and toxicity of biweekly administration of this drug in previously treated patients with advanced NSCLC. Methods: Patients with stage IIIB and IV NSCLC, which progressed after or during first-line chemotherapy, measurable disease, ECOG PS=0–1 and adequate organ function were included. Paclitaxel was administered at 150 mg/m2 iv, days 1 and 14, every 28 days, for a maximum of six cycles. Both, toxicity and efficacy analyses, were performed on the intent-to-treat (ITT) population. Results: Between September 2004 and November 2006, 42 patients (M/F, 39/3) were included, with median age 64 years (39–79). Tumor histology mainly included epidermoid (40.5%) and adenocarcinoma (35.7%). Tumor stage was IIIB (23.8%) and IV (76.2%). Median number of metastatic lesions was 1 (55%), located mainly in lymph nodes (30%), lung (25%), adrenal glands (16%) and bone (11%). Previous chemotherapy included platinum (76.1%), docetaxel (66.6%) and gemcitabine (52.4%). A total of 167 cycles (median 4, range 1–6) were administered. Median relative dose intensity was 94%. Toxicity: Grade III/IV hematologic toxicities per patient were neutropenia (2.5%) and anemia (2.5%). Grade III/IV non-hematologic toxicities were asthenia (2.5%), arthralgias/myalgias (2.5%) and peripheral neuropathy (2.5%). Efficacy: Of 39 ITT patients (3 patients have just begun chemotherapy), 7 achieved PR, 11 SD and 16 progressed, resulting in an ORR of 17.95% (95% CI: 5.9–30%). Five patients could not be evaluated for response due to early withdrawal (4 tumor-related exitus and 1 PS deterioration). Median TTP and OS were 174 days (95% CI: 115.52–232.48) and 332 days (95% CI: 261.18–402.82), respectively. Conclusions: Biweekly paclitaxel is an active and very well tolerated regimen in previously treated patients with advanced NSCLC. No significant financial relationships to disclose.

scholarly journals PL2.2 Pembrolizumab (PEM) in recurrent high-grade glioma (HGG)patients with mismatch repair deficiency (dMMR): an observational study

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii2-iii2
Author(s):  
M Caccese ◽  
M Simonelli ◽  
M Fassan ◽  
M Padovan ◽  
P Persico ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Brain Mri ◽  
High Grade Glioma ◽  
Median Number ◽  
Anaplastic Gliomas ◽  
Repair Deficiency ◽  
Grade 3 ◽  
Microsatellite Stability ◽  
Ecog Ps

Abstract BACKGROUND Pem, an immune checkpoint inhibitor, demonstrated to be activein various neoplasms with MMRd. No data exists about its efficacy in MMRdglioma patients. MATERIAL AND METHODS MMRd HGG relapsed after receiving RT and CT weretreated with Pem. MMR status was analyzed by immunohistochemistry,including the MLH1, MSH2, MSH6, and PMS2 markers. MMR deficiency wasdefined as presence of a weak (wMMRd) or absent (aMMRd) signal atimmunohistochemistry for at least one MMR protein. Other inclusion criteriawere: ECOG PS 0–2, histologically confirmed gliomas, dexamethasone ≤4 mg.Pem was administrated at 200 mg every 3 weeks until progression disease orunacceptable toxicity. Tumor response was evaluated by brain MRI every 10 weeksaccording to the RANO criteria. OS and PFS were evaluated by Kaplan-Meiercurves. CTCAE v4.0 was used for toxicity. RESULTS among 167 glioma patients, we found 22 MMRd gliomas. 12 PTS were treated with Pem: 8 wMMRd and 4 aMMRd. According to Bethesda criteria, allPTS had microsatellite stability. Tumor histologies included 5 anaplasticastrocytoma, 1 anaplastic oligodendroglioma, 6 glioblastoma (GBM). MSH2deficiency was found in 6 cases, MSH6 deficiency in 9 cases, PMS2 and MLH1deficiency in 2 cases. Median number of prior line of chemotherapy was 1 (range 1–5). Stable disease (SD) was reported in 4 PTS (33%); 8 PTS showedprogressive disease (PD). PTS with anaplastic gliomas showed a statisticallysignificant association with SD (p=0.03, OR=3); all GBM PTS reported PD; status of MMRd (weak/absent), IDH (mutated/wild-type), MSH2 and MLH6(deficient/proficient) were not associated with SD. Median follow up was 14.7 ms. OS was 5.6 ms (95% CI 0.1–13.8), PFS 2.4 ms (95% CI 1.8–2.9). OS was 2.8 ms and 5.6 ms (p=0.9), PFS was 1.8 ms and 3.1 ms (p=0.5) in PTS with wMMRd and aMMRd. PTS reporting SD and PD had PFS of 7.4 ms (95% CI 4.6–10.2) and 1.8 ms (95% CI 0.2–3.4), p=0.002; OS was “not reached” and 2.8 ms in PTS having SD vs PD (p=0.04). Grade ≥3 adverse eventswere reported in 8% of PTS. CONCLUSION a subgroup of recurrent MMRd HGG might benefit from Pem,especially anaplastic gliomas. There was a trend for a longer PFS and OS in PTS with aMMRd. Analyses for identifying additional molecular predictive factors is ongoing.

Testing targeted demethylation to overcome resistance to epidermal growth factor receptor (EGFR) blocking agents in wild-type (wt) KRAS metastatic colorectal cancer patients (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3057-3057 ◽  
Author(s):  
Ignacio Garrido-Laguna ◽  
Kimberly McGregor ◽  
Mark Wade ◽  
John R. Weis ◽  
Laura Burr ◽  
...  
Keyword(s):  
Cpg Island ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Median Number ◽  
Response To Therapy ◽  
Small Subset ◽  
Cpg Island Methylator Phenotype ◽  
Pik3ca Mutations ◽  
Previously Treated ◽  
Ecog Ps

3057 Background: Panitumumab, a monoclonal antibody against EGFR, led to improved progression-free survival (PFS) in patients with (wt)KRAS mCRC. However, the benefit of panitumumab is limited to a not yet identified small subset of (wt)KRAS patients. The CpG island methylator phenotype (CIMP-high) is present in 15-20% of CRC patients. Epigenetic silencing through methylation of PTEN and/or genes in the EGFR pathway might play a role in resistance to therapy. We assessed whether decitabine (a hypomethylating agent) reverted resistance to anti-EGFR therapies. Methods: Patients (n=19) with (wt)KRAS mCRC previously treated with anti-EGFR therapies were enrolled. Patients were treated with decitabine 45mg/kg IV on day (d)1 and d15 and panitumumab 6mg/kg IV on d8 and d22 q28days. Peripheral blood, skin biopsies and buccal smear samples were collected on d1, d8, d15 and d22 to assess methylation changes in PTEN, RASSF1A and SOCS-1 in response to therapy. Tumors were analyzed for PIK3CA mutations using PCR-based DNA sequencing of exon 9 and 20 by PCR as well as for PTEN by immunohistochemistry. Results: Median age was 53 (range 31-72). Eleven (58%) patients were female; 15 (79%) had ECOG PS 1; 3 (16%) had ECOG PS 2; and 1 had ECOG PS 0. Median number of previous therapies was 4. The most common toxicities were rash (68%), hypomagnesemia (26%) and neutropenia (10%) (all grade 1-2). The most common grade 3-4 toxicities were neutropenic fever (5%) and hypomagnesemia (5%). Of 19 (wt)KRAS mCRC patients previously treated with anti-EGFR therapies, 2 (11%) had a partial response (PR) (-50% and -30%, respectively) and 3 (16%) had stable disease (SD) >4 months (7.8, 5.9 and 4.2 months). Both responders were (wt)PIK3CA and (wt)PTEN. Clinical benefit rate (PR+SD) was 27%. Median PFS was 60 days (95% CI 45.4-74.5), similar to median PFS after last anti-EGFR therapy, 61d (95% CI 50.6-71.3). Conclusions: Panitumumab + decitabine is an active combination in a subset of patients with mCRC previously treated with anti-EGFR therapies (2 PRs in this population). Efficacy assessment in an anti-EGFR therapy naïve population is warranted. Methylation studies are ongoing.

Atezolizumab (atezo) in patients with metastatic urothelial carcinoma (mUC): A 2-year clinical update from a phase Ia study.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 290-290 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Thomas Powles ◽  
Joaquim Bellmunt ◽  
Fadi S. Braiteh ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Objective Response ◽  
The United States ◽  
Term Treatment ◽  
Long Term Results ◽  
Platinum Based Chemotherapy ◽  
Long Term Treatment ◽  
Previously Treated ◽  
Ecog Ps

290 Background: Atezo (anti–PD-L1) has demonstrated safety and efficacy in a broad range of cancers and is approved in the United States for mUC previously treated with platinum-based chemotherapy. Here we report long-term results in mUC from Phase Ia study NCT01375842 (PCD4989g). Methods: Previously treated mUC patients received atezo 15 mg/kg or 1200 mg IV q3w. Enrollment in this Phase Ia expansion cohort initially required PD-L1–selected status and later opened to patients regardless of PD-L1 expression on tumor-infiltrating immune cells. The primary endpoint was safety/tolerability. Secondary endpoints included investigator-assessed RECIST v1.1 ORR (confirmed), DOR and OS. Results: 95 patients were safety evaluable (Table). Median age was 66 years, 76% were male and 80% had primary bladder tumors. 61% had ECOG PS 1. 52% received ≥ 3 prior systemic therapies for mUC (70% platinum). Median treatment duration was 3 months (range: 0-32 months); 24% were treated for ≥ 1 year. Treatment-related AEs occurred in 66% (all Grade) and 8% (Grade 3-4) of patients. No treatment-related deaths were reported. In 94 objective response–evaluable patients (follow-up ≥ 12 weeks), the ORR was 27% (95% CI: 18, 37%), and the CR rate was 10%; the SD rate was 19%. mDOR was 22.1 months (95% CI: 12.1, NE months) in all patients; 56% of responses (7/9 CRs and 7/16 PRs) were ongoing at the December 15, 2015 data cutoff. With a 24-month median follow-up duration (range: 1+ to 32 months), the 1-year OS rate was 47% (95% CI: 36, 58%), and the 2-year rate was 29% (19, 40%); mOS is in the Table. Updated clinical data with further follow-up and analyses by PD-L1 status will be presented. Conclusions: Long-term treatment with atezo was well tolerated, without new safety signals in heavily pre-treated mUC patients. The durability of responses, including CRs, along with extended OS, confirm atezo as a new standard for previously treated mUC patients. Clinical trial information: NCT01375842. [Table: see text]

Ten-day decitabine with venetoclax (DEC10-VEN) in AML and high-risk (HR) MDS.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7519-7519 ◽  
Author(s):  
Abhishek Maiti ◽  
Courtney Denton Dinardo ◽  
Naveen Pemmaraju ◽  
Tapan M. Kadia ◽  
Caitlin R Rausch ◽  
...  
Keyword(s):  
Tumor Lysis Syndrome ◽  
Primary Objective ◽  
Prior Therapy ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Ecog Ps ◽  
Continue Therapy ◽  
Clinical Trial Information ◽  
Count Recovery

7519 Background: VEN-based low intensity regimens have shown promise in older pts with newly diagnosed (ND) AML. We hypothesized that adding VEN to 10-day (d) DEC may improve outcomes in AML and HR MDS. Methods: Pts received VEN 400 mg daily or equivalent with DEC 20 mg/m2 for 10d every 4-8 weeks for induction and DEC 5d with VEN for consolidation after CR/CRi. If cycle 1 day 21 bone marrow showed ≤5% blasts, VEN was held to enable count recovery. VEN duration could be further reduced for myelosuppression. FLT3 and IDH inhibitors were allowed for applicable pts. All pts received tumor lysis syndrome (TLS) prophylaxis. Primary objective was overall response rate (ORR). Secondary objectives were safety and overall survival (OS). Data cut-off date was February 6, 2020. Results: Between January 2018 and December 2019 we enrolled 184 pts with ND AML (>60 yrs), untreated secondary AML (sAML), treated sAML, relapsed/refractory (R/R) AML and HR MDS (Table). 58% pts were ≥70 yrs, 30% pts had ECOG PS ≥2, 67% pts had ELN adverse risk AML. Previously treated pts (n=96) had received a median of 1 prior therapy (range 1-8) including HMA (62), intensive chemotherapy (49) and stem cell transplantation (SCT, 27). 30d mortality was 3.3% and 60d mortality was 7.6%. 30d mortality in ND AML was 1.4%. Most common G3/4 adverse events were infections with G3/4 neutropenia (46%), febrile neutropenia (28%), infections with ANC ≥1x109/L (6%) and TLS (3%). Outcomes are shown in Table. 25 pts (14%) proceeded to SCT including treatment naive AML (ND+ untreated sAML, 12), previously treated AML (treated sAML + R/R, 11) and HR MDS (2). 100d post-SCT mortality was 4%. Median OS in treatment naïve AML pts undergoing SCT was not reached (1yr OS 100%) and for previously treated AML pts was 22.1 months (mo). After a median follow up of 15 mos, 25% PTS continue therapy. Additional analyses by molecular subgroups will be presented. Conclusions: DEC10-VEN is safe and highly effective in ND AML and can serve as an effective bridge to SCT in previously treated pts. Trial continues to accrue (NCT03404193). Clinical trial information: NCT03404193 . [Table: see text]

Salvage vinorelbine (VNR) in the 2nd to 4th line setting in advanced non-small cell lung cancer (NSCLC): A retrospective review at the Fox Chase Cancer Center (FCCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17072-17072
Author(s):  
J. G. Devlin ◽  
C. J. Langer
Keyword(s):  
Systemic Therapy ◽  
Stage Iv ◽  
Response Rates ◽  
Median Number ◽  
Salvage Treatment ◽  
Disease Assessment ◽  
Cancer Center ◽  
Number Of Patients ◽  
Line Setting ◽  
Ecog Ps

17072 Background: Published literature has demonstrated minimal activity for VNR in the salvage treatment of NSCLC, with response rates of only 0.8% (Fossella, et al, JCO 2000; 18(12), 2354–2362). However, in our clinical experience, we have observed a number of patients (pts) with clinical benefit. Methods: Retrospective evaluation was performed of all pts with NSCLC who had received VNR at FCCC from 6/02–6/05 in the salvage setting. Pts were evaluable if full medical records (including radiographic imaging for disease assessment) were available, had received ≥2 cycles of VNR, and had advanced, recurrent or metastatic NSCLC. Primary endpoint was response rate (RR); secondary endpoints included safety, median overall survival (OS), and median time to progression (TTP). Results: 52 pts were included, 28 pts were ultimately evaluable (13 pts received <2 cycles of VNR, 7 pts did not have NSCLC, and 4 pts received VNR with RT or other agents). Median age was 64 yrs, 64% were female; ECOG-PS 0–18%, 1–50%, 2–28.5%, 3–3.5%. 82% exhausted 2 lines of systemic therapy before VNR; 32% exhausted 3; 21.4% received prior EGFR-TKI; 18% received other prior protocol therapies. 96.3% of pts had stage IV, stage IIIB, or recurrent disease. 21.4% had bone mets; 25% had brain mets; and 42.8% had visceral metastases. 85.8% had significant comorbidities. Median number of VNR cycles was 4. RR:PR 10.7%, SD/MR 35.7%, and PD 50%. 25% required dose reductions, predominantly for gr 4 hematologic toxicities. Non-hematologic toxicities were generally mild, and included neuropathy, fatigue and GI distress; there were no Tx-related deaths. 32% were able to receive other systemic therapy after VNR. Median OS was 5 months, and median TTP was 3 months. Conclusions: Vinorelbine is active and relatively well-tolerated in the salvage treatment of NSCLC, including heavily pretreated pts. Response rates exceed that observed in the literature. [Table: see text]

Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1008-1008 ◽  
Author(s):  
Sylvia Adams ◽  
Peter Schmid ◽  
Hope S. Rugo ◽  
Eric P. Winer ◽  
Delphine Loirat ◽  
...  
Keyword(s):  
Primary Endpoints ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Grade 3 ◽  
Ecog Ps

1008 Background: In KEYNOTE-012, pembro showed durable activity and manageable safety in patients (pts) with PD-L1+ mTNBC. Cohort A of KEYNOTE-086 (NCT02447003) examined the efficacy/safety of pembro in previously treated mTNBC, regardless of PD-L1 expression. Methods: Pts with centrally confirmed mTNBC, ≥1 prior chemotherapy for metastatic disease, and ECOG PS 0-1 had pembro 200 mg Q3W for up to 24 mo; imaging q 9 wk for the first 12 mo, then q 12 wk. Clinically stable pts with PD could remain on pembro until PD confirmed on next assessment. Primary endpoints: ORR (RECIST v1.1, central review) in all pts and pts with PD-L1+ tumors, and safety. Secondary endpoints: DOR, disease control rate (DCR; CR + PR + SD ≥24 wk), PFS, and OS. Planned enrollment was 160 pts; analysis based on data as of Nov 10, 2016. Results: 60% of screened PD-L1-evaluable pts had PD-L1+ tumors (combined positive score ≥1%). Of 170 pts enrolled (100% women; median age 54 y), 44% had ≥3 prior lines of therapy, 51% had elevated LDH, 74% had visceral mets and 62% had PD-L1+ tumors. After a median follow-up of 10.9 mo, 9 (5%) pts remained on pembro. Treatment-related AEs (TRAEs) of any grade and grade 3-4 occurred in 60% and 12% of pts, respectively; 4% discontinued due to TRAEs. There were no deaths due to AE. Overall ORR was 5% regardless of PD-L1 expression (Table). Best overall response was 0.6% CR, 4% PR, 21% SD; not evaluable (3%). DCR was 8% (95% CI 4-13). Median DOR was 6.3 mo (range 1.2+ to 10.3+); 5 (63%) responders w/o PD at data cutoff. Median PFS and OS were 2.0 mo (95% CI 1.9-2.0) and 8.9 mo (95% CI 7.2-11.2), with 6-mo rates of 12% and 69%, respectively. ORR was numerically lower in pts with poor prognostic factors (e.g., high LDH, liver/visceral mets; Table). Conclusions: In KEYNOTE-086 Cohort A, pembro monotherapy showed manageable safety and durable responses in a subset of pts with heavily pretreated mTNBC. Randomized studies of monotherapy and combination therapy are ongoing. Clinical trial information: NCT02447003. [Table: see text]

Pembrolizumab (Pem) in recurrent high-grade glioma (HGG) patients (PTS) with mismatch repair deficiency (MMRd): An observational study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2043-2043
Author(s):  
Giuseppe Lombardi ◽  
Mario Caccese ◽  
Matteo Simonelli ◽  
Matteo Fassan ◽  
Marta Padovan ◽  
...  
Keyword(s):  
Brain Mri ◽  
High Grade Glioma ◽  
Median Number ◽  
Kaplan Meier ◽  
Anaplastic Gliomas ◽  
Repair Deficiency ◽  
Grade 3 ◽  
Microsatellite Stability ◽  
Ecog Ps

2043 Background: Pem, an immune checkpoint inhibitor, demonstrated to be active in various neoplasms with MMRd. No data exists about its efficacy in MMRd glioma PTS. Methods: MMRd HGG relapsed after receiving RT and CT were treated with Pem. MMR status was analyzed by immunohistochemistry, including the MLH1, MSH2, MSH6, and PMS2 markers. MMRd was defined as presence of a weak (wMMRd) or absent (aMMRd) signal for at least one MMR protein. Other inclusion criteria were: ECOG PS 0-2, histologically confirmed glioma, dexamethasone ≤4 mg. Pem was administrated at 200 mg every 3 weeks until disease progression or unacceptable toxicity. Tumor response was evaluated by brain MRI every 10 weeks according to the RANO criteria. OS and PFS were evaluated by Kaplan-Meier curves. Results: among 167 glioma PTS, we found 22 MMRd gliomas. 12 PTS were treated with Pem: 8 wMMRd and 4 aMMRd. According to Bethesda criteria, all PTS had microsatellite stability. Tumor histologies included 5 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, 6 glioblastoma (GBM). MSH2 deficiency was found in 6 cases , MSH6 deficiency in 9 cases, PMS2 and MLH1 deficiency in 2 cases. Median number of prior lines of chemotherapy was 1 (range 1-5). Stable disease (SD) was reported in 4 PTS (33%); 8 PTS showed progressive disease (PD). PTS with anaplastic gliomas showed a statistically significant association with SD (p=0.03, OR=3); all GBM PTS reported PD; status of MMRd (weak/absent), IDH (mutated/wild-type), MSH2 and MLH6 (deficient/proficient) were not associated with SD. Median follow up was 14.7 ms. OS was 5.6 ms (95% CI 0.1-13.8), PFS 2.4 ms (95% CI 1.8-2.9). OS was 2.8 ms and 5.6 ms (p=0.9), PFS was 1.8 ms and 3.1 ms (p=0.5) in PTS with wMMRd and aMMRd, respectively. PTS reporting SD and PD had PFS of 7.4 ms (95% CI 4.6-10.2) and 1.8 ms (95% CI 0.2-3.4), p=0.002; OS was “not reached” and 2.8 ms in PTS having SD vs PD (p=0.04), respectively. Grade ≥3 adverse events were reported in 8% of PTS. Conclusions: a subgroup of recurrent MMRd HGG might benefit from Pem, especially anaplastic gliomas. There was a trend for a longer PFS and OS in PTS with aMMRd. The enrollment and analyses for identifying additional molecular predictive factors are ongoing.

Trifluridine/tipiracil (FTD/TPI) in patients (pts) aged ≥65 years with metastatic gastric/gastroesophageal junction cancer (mGC/mGEJC): Subgroup analysis from TAGS.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4037-4037 ◽  
Author(s):  
Kohei Shitara ◽  
Toshihiko Doi ◽  
Hisashi Hosaka ◽  
Peter C. Thuss-Patience ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Gastroesophageal Junction ◽  
The Elderly ◽  
Best Supportive Care ◽  
Moderate Renal Impairment ◽  
Treatment Groups ◽  
Gastroesophageal Junction Cancer ◽  
Previously Treated ◽  
Dose Modifications ◽  
Ecog Ps

4037 Background: 60% of newly diagnosed GC pts are > 65 y of age, a proportion that is increasing. The global phase 3 study TAGS (NCT02500043) demonstrated the efficacy and safety of FTD/TPI in previously treated pts with mGC/mGEJC. Here we report results in the pt subgroup aged ≥65 in TAGS. Methods: Pts with mGC/mGEJC treated with ≥2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. A preplanned efficacy/safety analysis was performed in pts aged ≥65 y. Results: Of 507 randomized pts, 228 (45%) were aged ≥65 y (range 65–89). The pt subset aged ≥65 y was similar to the overall population, except for a higher incidence of moderate renal impairment in the elderly subgroup (31% vs 17%). For pts aged ≥65 y, baseline characteristics were generally balanced across the treatment groups, although more pts treated with FTD/TPI than with placebo had ECOG PS 1 (69% vs 59%). FTD/TPI had an efficacy benefit in pts aged ≥65 y, and the FTD/TPI safety profile was similar in this subgroup vs the overall population (table). Treatment-related deaths (one in each treatment group) did not occur in pts aged ≥65 y. No drug-related deaths associated with cardiotoxicity were reported in pts aged ≥65 y. Although dose modifications were used more often in this subgroup, there was no increase in discontinuations vs the overall population. Conclusions: FTD/TPI was safe and effective in pts aged ≥65 y, who had a higher incidence of moderate renal impairment vs the overall population. Clinical trial information: NCT02500043. [Table: see text]

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