Circulating tumor DNA (ctDNA) in metastatic melanoma (MM) patients (pts) with brain metastases (mets).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9581-9581
Author(s):  
Jenny HJ Lee ◽  
Alexander M. Menzies ◽  
Matteo S. Carlino ◽  
Richard Kefford ◽  
Richard A. Scolyer ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Detection Threshold ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Brain Response ◽  
Free Survival ◽  
Best Response ◽  
Droplet Pcr ◽  
Extracranial Disease

9581 Background: Brain mets are common in pts with MM, occurring in up 50% of pts. Serial ctDNA levels at baseline and early on therapy predict objective response (OR) and overall survival (OS) in MM pts without brain mets receiving immune checkpoint inhibitors (ICI). The predictive utility in pts with brain mets is unknown. Methods: BRAF/NRAS ctDNA at baseline and early on ICI therapy (week 3-8) was analysed using mutation specific digital droplet PCR (detection threshold 2.5 copies/ml plasma) in MM pts with brain mets. Intracranial (IC) and extracranial (EC) disease volume (sum of product of diameters of ALL mets [SPD]) and OR, progression-free survival (PFS) and OS were analyzed. Results: 48 pts with brain mets were studied, 40 with concurrent EC disease (SPD EC med 892mm2 [25-22417mm2], IC med 200mm2 [9-1487mm2]) and 8 with isolated IC mets (SPD med 150mm2 [66-1035mm2]). At baseline, ctDNA was detectable in 28 (58%) pts, 28/40 (70%) with IC + EC mets and 0/8 with isolated IC mets. Baseline ctDNA reflected EC disease volume (Pearson’s r = 0.4, p = 0.01) but not IC volume (r = 0.1, p = 0.5). Baseline ctDNA did not associate with IC or EC OR or PFS, however, undetectable ctDNA was associated with superior OS (HR 0.4, p = 0.01). Early on therapy, ctDNA predicted EC response but not IC response; EC OR was 65% if ctDNA undetectable and 6% if detectable (p < 0.01), IC OR was 35% if undetectable and 12% if detectable (p = 0.1). Nevertheless, undetectable ctDNA early on therapy was associated with a superior PFS (HR 0.3, p < 0.01) and OS (HR 0.2, p < 0.01), indicating survival is largely determined by extracranial disease activity. In the 8 pts with IC disease only, 7/8 had disease progressive disease as best response. 1/8 subsequently developed detectable ctDNA at week 12, with multiple new EC mets seen at first restaging scan at this time. Conclusions: ctDNA does not appear to be a useful biomarker for detecting brain mets nor monitoring brain response in melanoma pts receiving ICI. This has important implications when using ctDNA in the setting of surveillance in the metastatic and adjuvant setting.

scholarly journals Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors

2020 ◽  
Vol 38 (27) ◽  
pp. 3088-3094 ◽  
Author(s):  
Anita Gul ◽  
Tyler F. Stewart ◽  
Charlene M. Mantia ◽  
Neil J. Shah ◽  
Emily Stern Gatof ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Rcc

PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

Gefitinib in second line treatment of metastatic or locally advanced synovial sarcoma expressing HER1: A phase II trial of EORTC Soft Tissue and Bone Sarcoma Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9517-9517 ◽  
Author(s):  
J. Blay ◽  
A. Le Cesne ◽  
J. Whelan ◽  
A. Van Oosterom ◽  
I. Ray-Coquard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Soft Tissue ◽  
Primary Endpoint ◽  
Objective Response ◽  
Locally Advanced ◽  
Specific Inhibitor ◽  
Progression Free Survival ◽  
Bone Sarcoma ◽  
Free Survival ◽  
Best Response

9517 Background: Synovial sarcomas (SyS) have been reported to overexpress HER1 in gene expression profile experiments and immunohistochemistry. Gefitinib, a specific inhibitor of HER1, was therefore tested in advanced or metastatic SyS failing doxorubicin (Doxo) ± ifosfamide (Ifo). Methods: Patients (pts) with advanced or metastatic SyS expressing HER1 using IHC were included. The principal inclusion criterias were: disease not curable with surgery and/or radiation, presence of a measurable progressive lesion(s), pretreatment with 1–3 line of chemotherapy in metastatic phase, ECOG PS 0 to 2, age ≥18 years. Gefitinib was given at 500mg/day until progression or intolerance. Primary endpoint was the rate of progression free survival at 3 months. A two step Simon design was used with a p0 of 25% and a p1 of 45%, with α and β of 0.1. 44 patients were scheduled to be recruited. Results: Between 10/02 and 10/05, 48 pts were included in 12 EORTC STBSG centers, 27 (56%) males and 21 (44%) females. Median age was 42 years (range 19–66). Metastatic sites were lung in 92% and soft tissue or lymph nodes in 42%, of the patients. Respectively 42, 40 and 18% of the patients had received 1, 2 and >2 lines of CT. As of December 2005, 37 pts are evaluable for toxicity and 39 for the primary endpoint. Median treatment duration was 11 weeks (range 2–25). Toxicity (G1–4) reported included fatigue (43%), diarrhea (54%), cough (35%), dyspnea (43%), cutaneous (73%). G3–4 toxicities were dyspnea (9), fatigue (4), cutaneous (2), cough (1), neurological (2), thombosis (2), hypoxia (1), infection (1). There was no drug related death. No dose reduction has been reported so far, but treatment had to be temporarily interrupted in 23% of the patients. As of December 2005, there were no objective response reported. Seven (18%) pts achieved stable disease as best response. At 3 months, 5 of the 39 (13%) evaluable patients achieved PFS; 6 and 12 months PFS were 10% and 3% respectively. Conclusions: 13% of SyS expressing HER1 achieved prolonged progression free survival at least 12 weeks) with gefitinib. Gene expression profiling and protein expression were not accurate predictors of gefitinib activity in this model. No significant financial relationships to disclose.

Real-world (rw) clinical outcomes for advanced/metastatic non-small cell lung cancer (aNSCLC) patients (pts) treated with second line (2L) ramucirumab plus docetaxel (R+D) post frontline (1L) platinum based chemotherapy plus immune checkpoint inhibitors (Pt + ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20727-e20727
Author(s):  
Jeffrey Melson Clarke ◽  
Raina Mathur ◽  
Cliff Molife ◽  
Marta Batus ◽  
Victoria Jennifer Stefaniak ◽  
...  
Keyword(s):  
Disease Control ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Community Practice ◽  
Best Response ◽  
First Response ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response

e20727 Background: R+D is approved for use in pts with aNSCLC after Pt chemotherapy. With recent approvals, ICI can now be added to Pt chemotherapy (Pt + ICI) in 1L. This retrospective observational study provides an exploratory view of baseline characteristics and rw clinical effectiveness outcomes for pts receiving 2L R+D post 1L Pt + ICI. Methods: All adult pts treated with 2L R+D after 1L Pt + ICI therapy between 03/01/2015 and 06/30/2018, with ≥ 3 months follow up, were selected from the Flatiron Health EHR-derived de-identified database (n = 15). Rw clinical endpoints during R+D therapy included rw objective response rate (rwORR), rw disease control rate (rwDCR), rw best response, as well as Kaplan-Meier estimates of rw time to first response & rw duration of response. Results: Median age was 62 years, 10 pts (66.6%) were aged < 65 years, 11 (73.3%) were men, 3 (20.0%) had no history of smoking, 14 (93.3%) had non-squamous histology, 4 (26.7%) were EGFR positive, 3 (20.0%) were KRAS positive and 6 (85.7%) were PD-L1 negative. Of the 8 pts with a documented rw tumor response assessment, 3 (37.5%) had partial response (PR), 3 (37.5%) had stable disease (SD), & 2 (25.0%) had progressive disease as their rw best response. The rwORR (PR or complete response [CR]) & rwDCR (PR, CR, or SD) were 37.5% and 75.0%, respectively. Among responding pts, median time to first response was 2.2 months (95% CI, 1.3 - not reached [NR]) & median duration of response was 2.3 months (95% CI, 1.5 - NR). Patient numbers were too small (n = 15) and duration of follow-up was too short (3.4 months [IQR, 0.7 - 5.4]) to make robust estimation of overall survival or rw progression free survival. Conclusions: Data from this small patient cohort in US community practice are not conclusive and should be considered exploratory, but do show high rates of rw objective response and rw disease control rates during 2L R+D following 1L Pt + ICI. Data with larger sample sizes and additional follow-up are needed to better understand outcomes of R+D following the addition of ICI to 1L Pt chemotherapy regimens.

Efficacy of first-line immune checkpoint inhibitors in patients with sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC).

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 66-66
Author(s):  
Ziad Bakouny ◽  
Sarah Abou Alaiwi ◽  
Amin Nassar ◽  
John A. Steinharter ◽  
Xiao X. Wei ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Logistic Regressions

66 Background: Patients with mRCC with S/R components tend to have a poor prognosis with few therapeutic options available. Recent data suggest that immune checkpoint inhibitor (ICI)-based therapies may be especially effective for these patients. Our aim was to evaluate the efficacy of ICI-based therapies in patients with S/R mRCC. Methods: We retrospectively assessed objective response rate (ORR), progression free survival (PFS) & overall survival (OS) of patients with S/R mRCC treated at our institution with first-line ICI-based therapies and compared these to those of patients treated with first-line non-ICI-based therapies. Univariable and multivariable (adjusted for IMDC group) Cox and logistic regressions were performed. Results: 92 patients (70 S, 9 R, and 13 S&R) patients were included, of which 74 with a clear-cell component. For all patients (regardless of therapy), 74 (80.4%) patients experienced a PFS event (progression or death) and 52 (56.5%) died at 25.3 months (m) median follow-up. Overall median PFS was 5.3 m (95% CI= 3.4–7.2) and 24 m OS rate was 39.5% (27.4–51.7). Out of 78 patients in whom response was evaluable, ORR was 30.8% (20.4–41.2). Patients treated with ICI-based therapies had significantly better ORR, PFS, and OS on multivariable analysis (table). Conclusions: mRCC patients with S/R components have significantly better ORR, PFS, and OS with first-line ICI-based compared to non-ICI-based therapies. These data support the use of ICI-based therapies for patients with S/R mRCC. [Table: see text]

Clinicopathologic and genomic correlates of tumor-infiltrating immune cells and immunotherapy efficacy in NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9121-9121
Author(s):  
Joao Victor Machado Alessi ◽  
Biagio Ricciuti ◽  
Mizuki Nishino ◽  
Jason L. Weirather ◽  
Ann-Elisabeth Le ◽  
...  
Keyword(s):  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinicopathological Characteristics ◽  
Free Survival ◽  
Oncogenic Driver ◽  
Optimal Cluster

9121 Background: Tumor-infiltrating immune cells and PD-L1 expression are associated with improved clinical outcomes in patients (pts) with NSCLC treated with immune checkpoint inhibitors (ICIs). However, as tumor-infiltrating immune cells are not a well-established biomarker for NSCLC, further data are needed to integrate and identify clinicopathological and genomic factors that influence the tumor microenvironment. Methods: We collected clinicopathologic and genomic data from pts with NSCLC who underwent multiplexed immunofluorescence. Uniform Manifold Approximation and Projection (UMAP) was used to identify distinct immunophenotypic clusters according to the number of intratumoral PD-1+ immune cells (ICs), CD8+, and Foxp3+ T cells, as well as PD-L1 on tumor and immune cells. An unbiased recursive partitioning (URP) algorithm was used to investigate an optimal cluster with respect to objective response rate (ORR) in the subset of pts treated with ICIs. Results: Among 304 pts, UMAP identified 5 clusters: PD-L1-high with high vs low CD8+ and PD-1+ ICs (clusters A & B, respectively); PD-L1-low with high vs low CD8+ and PD-1+ ICs (clusters C & D respectively); PD-L1-low and moderate levels of CD8+ and PD-1+ ICs (cluster E). Clinicopathological characteristics of the clusters shown in Table. URP analysis identified immune rich clusters A and C as optimal responders to ICIs. From the start of ICIs, we observed a significantly higher ORR (53.3% vs 4.3%; P<0.001), a significantly longer median progression-free survival (mPFS 25.6 vs 3.7 months; HR: 0.12 [95% CI: 0.05-0.32]; P<0.001), and longer median overall survival (mOS 45.1 vs 22.3 months; HR: 0.25 [95% CI: 0.1-0.68]; P=0.006) in clusters A + C (N=15) vs other clusters (N=23). After adjusting for other variables such as performance status, histology, presence of oncogenic driver mutation, and line of treatment, clusters A + C were significantly associated with improved mPFS (HR: 0.08 [95% CI: 0.03-0.24], P<0.001) and mOS (HR: 0.11 [95% CI: 0.03-0.40], P<0.001). Conclusions: Incorporation of multiplex immunofluorescence may improve prediction of response and resistance to immunotherapy in NSCLC.[Table: see text]

scholarly journals Immune Checkpoint Inhibitors in Advanced Acral Melanoma: A Systematic Review

2020 ◽  
Vol 10 ◽  
Author(s):  
Qingyue Zheng ◽  
Jiarui Li ◽  
Hanlin Zhang ◽  
Yuanzhuo Wang ◽  
Shu Zhang
Keyword(s):  
Systematic Review ◽  
Combination Therapy ◽  
Objective Response Rate ◽  
Median Overall Survival ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Therapeutic Effects ◽  
Free Survival

IntroductionAcral melanoma (AM) has different biological characteristics from cutaneous melanoma. Although systemic therapeutic strategies for advanced AM resemble those for advanced cutaneous melanoma, the evidence of the clinical use of immune checkpoint inhibitors (ICIs) for AM is still inadequate. We aimed to systematically analyze the therapeutic effects and safety profile of ICI treatments in advanced AM.MethodsThis systematic review was conducted in line with a previously registered protocol. Three electronic databases, conference abstracts, clinical trial registers, and reference lists of included articles were searched for eligible studies. The primary outcomes were therapeutic effects, and the secondary outcomes were the safety profiles.ResultsThis systematic review included six studies investigating anti-CTLA-4 immunotherapy, 12 studies investigating anti-PD-1 immunotherapy, one study investigating the combination therapy of anti-CTLA-4 and anti-PD-1, and one study investigating anti-PD-1 immunotherapy in combination with radiotherapy. In most studies investigating ipilimumab, the anti-CTLA-4 antibody, the objective response rate ranged from 11.4 to 25%, the median progression-free survival ranged from 2.1 to 6.7 months, and the median overall survival was more than 7.16 months. For studies discussing anti-PD-1 immunotherapy with nivolumab, pembrolizumab, or JS001, the objective response rate ranged from 14 to 42.9%, the median progression-free survival ranged from 3.2 to 9.2 months, and the median overall survival was more than 14 months. The combination therapy of anti-CTLA-4 and anti-PD-1 immunotherapy showed better efficacy with an objective response rate of 42.9% than single-agent therapy. The retrospective study investigating the combination therapy of anti-PD-1 immunotherapy and radiation showed no overall response. Few outcomes regarding safety were reported in the included studies.ConclusionsICIs, especially anti-CTLA-4 monoclonal antibodies combined with anti-PD-1 antibodies, are effective systematic treatments in advanced AM. However, there remains a lack of high-level evidence to verify their efficacy and safety and support their clinical application.

Outcomes of patients (pts) with metastatic clear-cell renal cell carcinoma (mCCRCC) treated with second-line (2L) vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after first-line (1L) immune checkpoint inhibitors (ICI).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 682-682 ◽  
Author(s):  
Amishi Yogesh Shah ◽  
Emily Lemke ◽  
Jianjun Gao ◽  
Anuradha Chandramohan ◽  
Matthew T. Campbell ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Impaired Wound Healing ◽  
Kaplan Meier ◽  
Best Response

682 Background: Little data exists on objective response rates (ORR), progression-free survival (PFS), and safety of 2L VEGFR-TKI after 1L ICI therapy in pts with mCCRCC. Methods: This is a retrospective study of pts with mCCRCC who received 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Tumor response was assessed by a blinded radiologist using RECIST 1.1. Descriptive statistics, the Fisher’s test, and Kaplan-Meier method were used. Results: We report on 43 pts who were treated at MDACC from 2015 till present. Median age at mCCRCC diagnosis was 59 years (range: 43-72). 33 pts had lung mets, 20 had LN mets, 14 had bone mets, and 3 had liver mets. As 1L therapy, 20 pts received nivolumab + ipilimumab, 14 received nivolumab + bevacizumab, and 9 received nivolumab. Median time on ICI therapy was 29.4 weeks. All pts had resolution of Grade 3/4 AEs from ICI and PD before initiation of VEGFR-TKI. One patient (2%) had CR, 17 pts (40%) had PR, and 25 pts (58%) had SD, leading to 100% disease control rate (DCR) as best response to 2L VEGFR-TKI. Median PFS was 10.0 months (95% CI: 7.4, NA). Estimated 1-yr overall survival (OS) was 87.5% (95% CI: 74.6 - 100). Seven pts (16%) discontinued VEGFR-TKI therapy because of AEs: Gr 3 transaminitis (3 on pazopanib), Gr 3 hand-foot skin reaction (1 on axitinib), impaired wound healing (1 on axitinib), and Gr 3 pancreatitis (1 on pazopanib, 1 on axitinib). Conclusions: In this retrospective study, we observed a 42% ORR, a 10-month median PFS, and a 100% DCR in pts with mCCRCC who received VEGFR-TKI after PD with ICI. These results inform the design of trials with 2L VEGFR-TKI after failure of ICI therapy. [Table: see text]

scholarly journals Real-world outcomes of regorafenib combined with immune checkpoint inhibitors in patients with advanced or metastatic microsatellite stable colorectal cancer: A multicenter study

2021 ◽  
Author(s):  
Kaili Yang ◽  
Lu Han ◽  
Shikai Wu ◽  
Xiujuan Qu ◽  
Qin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Best Response

Abstract Background Treatment strategies are limited for patients with chemotherapy refractory microsatellite stable (MSS) colorectal cancer. We aim to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with regorafenib in this population in routine clinical practice. Methods We retrospectively analyzed patients with advanced or metastatic colorectal cancer who received at least one dose of ICIs combined with regorafenib in 14 Chinese medical centers. The primary outcome was objective response rate (ORR). This study was registered at ClinicalTrials.gov on February 2020 (NCT04771715). Results Eighty-four patients received ICIs combined with regorafenib from January 2019 to January 2021. Most patients (91%) received two or more systemic treatment lines before the study treatment. Seventy-six patients (90%) had confirmed MSS status. At a median follow-up of 5.5 months, four patients achieved partial response (5%) and 37 patients achieved stable disease (45%) as the best response. The median progression-free survival (PFS) was 3.1 months, and the median overall survival was 17.3 months. Eleven patients (13%) remained progression-free for more than 6 months. Baseline liver metastasis (HR 1.98, 95%CI 1.07–3.69, P = 0.03) and neutrophil–lymphocyte ratio (NLR) of ≥ 1.5 (HR 2.83, 95%CI 1.00–7.98, P = 0.05) were associated with shorter PFS in multivariate analysis. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 16 patients (19%). Conclusion The combination of ICIs with regorafenib can be a valuable treatment option for a proportion of patients with chemotherapy refractory MSS colorectal cancer. Patients with no liver metastasis and a low NLR at baseline may derive most benefit from this strategy.

scholarly journals BRAF Inhibition in BRAFV600-Mutant Gliomas: Results From the VE-BASKET Study

2018 ◽  
Vol 36 (35) ◽  
pp. 3477-3484 ◽  
Author(s):  
Thomas Kaley ◽  
Mehdi Touat ◽  
Vivek Subbiah ◽  
Antoine Hollebecque ◽  
Jordi Rodon ◽  
...  
Keyword(s):  
Stable Disease ◽  
Pilocytic Astrocytoma ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Diffuse Glioma ◽  
Histologic Subtype ◽  
Free Survival ◽  
Best Response

Purpose BRAFV600 mutations are frequently found in several glioma subtypes, including pleomorphic xanthoastrocytoma (PXA) and ganglioglioma and much less commonly in glioblastoma. We sought to determine the activity of vemurafenib, a selective inhibitor of BRAFV600, in patients with gliomas that harbor this mutation. Patients and Methods The VE-BASKET study was an open-label, nonrandomized, multicohort study for BRAFV600-mutant nonmelanoma cancers. Patients with BRAFV600-mutant glioma received vemurafenib 960 mg twice per day continuously until disease progression, withdrawal, or intolerable adverse effects. Key end points included confirmed objective response rate by RECIST version 1.1, progression-free survival, overall survival, and safety. Results Twenty-four patients (median age, 32 years; 18 female and six male patients) with glioma, including malignant diffuse glioma (n = 11; six glioblastoma and five anaplastic astrocytoma), PXA (n = 7), anaplastic ganglioglioma (n = 3), pilocytic astrocytoma (n = 2), and high-grade glioma, not otherwise specified (n = 1), were treated. Confirmed objective response rate was 25% (95% CI, 10% to 47%) and median progression-free survival was 5.5 months (95% CI, 3.7 to 9.6 months). In malignant diffuse glioma, best response included one partial response and five patients with stable disease, two of whom had disease stabilization that lasted more than 1 year. In PXA, best response included one complete response, two partial responses, and three patients with stable disease. Additional partial responses were observed in patients with pilocytic astrocytoma and anaplastic ganglioglioma (one each). The safety profile of vemurafenib was generally consistent with that of previously published studies. Conclusion Vemurafenib demonstrated evidence of durable antitumor activity in some patients with BRAFV600-mutant gliomas, although efficacy seemed to vary qualitatively by histologic subtype. Additional study is needed to determine the optimal use of vemurafenib in patients with primary brain tumors and to identify the mechanisms driving differential responses across histologic subsets.

Prevalence and outcomes of patients (pts) with EGFR S492R ectodomain mutations in ASPECCT: Panitumumab (pmab) vs. cetuximab (cmab) in pts with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 740-740 ◽  
Author(s):  
Timothy Jay Price ◽  
Kathryn Newhall ◽  
Marc Peeters ◽  
Tae Won Kim ◽  
Jin Li ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Exon 2 ◽  
Free Survival ◽  
Droplet Pcr ◽  
Secondary Endpoints ◽  
To Receive ◽  
Clinical Trial Information

740 Background: Mutations resistant to anti-EGFR treatment (tx), beyond those in RAS, have been reported and include EGFR S492R. We report results for pts with EGFR S492R mutations in the phase 3 ASPECCT trial. Methods: Pts were randomized 1:1 to receive pmab or cmab. Crossover was not allowed. The primary endpoint was non-inferiority of overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. EGFR S492R was evaluated by digital droplet PCR in plasma samples collected pre-tx and post-tx (safety follow-up 4 wks after the last dose). Outcomes were analyzed by EGFR S492 status. Results: Of 999 pts randomized and treated, post-tx samples were available for EGFR S492 assessment from 53% of pts (261/496) in the pmab arm and 57% of pts (285/503) in the cmab arm. EGFR S492R was detected in 1% of pts in the pmab arm and 16% of pts in the cmab arm in post-tx samples. EGFR S492R was not detected in pre-tx samples. Results are shown (table). Conclusions: In a retrospective analysis of pts with available samples from ASPECCT, 16% of pts in the cmab arm and 1% of pts in the pmab developed EGFR S492R mutations. Pts with EGFR S492R in the cmab arm had longer tx duration before progressive disease (PD) and appeared to have worse OS vs pts with wild-type S492 in the cmab arm. Clinical trial information: NCT01001377. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document