Chemotherapy with erlotinib or chemotherapy alone in advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitors (TKI).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7524-7524 ◽  
Author(s):  
Sarah B. Goldberg ◽  
Geoffrey R. Oxnard ◽  
Subba Digumarthy ◽  
Alona Muzikansky ◽  
David Michael Jackman ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Objective Response ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Rank Test ◽  
Significant Difference ◽  
Tki Resistance ◽  
Egfr Tkis

7524 Background: EGFR-mutant NSCLC has an oncogene-addicted phenotype that confers sensitivity to EGFR TKIs. Prior data suggests EGFR addiction persists after development of TKI resistance, leading many clinicians to continue TKI along with chemotherapy (chemo); however, this strategy has not been formally evaluated. Methods: An institutional database was reviewed to identify patients (pts) with advanced NSCLC and acquired resistance to EGFR TKIs by Jackman criteria. Pts were included if they subsequently received chemo. Objective response rate (RR) to chemo/erlotinib or chemo alone was assessed by blinded radiographic review and compared by Fisher’s exact test and multivariable logistic regression. Progression-free survival (PFS) and overall survival (OS) from TKI failure (defined as chemo initiation date) were compared by log-rank test and multivariable Cox analysis. Results: 78 pts were eligible (34 chemo/erlotinib, 44 chemo alone). 70 pts (90%) had a documented EGFR mutation and were on TKI for a median of 15 months (range 4-51); in the 8 pts with unknown genotype the median duration on TKI was 11 months (range 5-16). Baseline characteristics were well balanced except more pts received erlotinib as initial TKI in the chemo/erlotinib group. RR was evaluable in 57 pts and was higher with chemo/erlotinib compared to chemo alone (41% vs 18%; OR 0.31, 95% CI 0.09, 1.04; p=0.08). RR adjusted for chemo regimen and time to TKI failure yielded OR 0.20 (95% CI 0.05, 0.78; p=0.02), favoring chemo/erlotinib. Median PFS was 4.4 months in the chemo/erlotinib group and 4.2 months in the chemo alone group (crude HR=0.84, 95% CI 0.52, 1.38; p=0.50; adjusted HR 0.79, 95% CI 0.48, 1.29; p=0.34). There was no significant difference in OS in the crude or adjusted analyses. Conclusions: This is the first study, to our knowledge, to show that continuation of an EGFR TKI with chemo compared to chemo alone significantly increases the RR in pts with advanced NSCLC and acquired TKI resistance, though we did not observe an impact on PFS or OS. Continued concurrent TKI may be a valuable strategy, particularly for pts with symptomatic progression, when a higher response rate may be beneficial. Further study is warranted.

Comparison of circulating tumor DNA (ctDNA) sequencing and tumor-based genotyping for the detection of EGFR mutations in non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20586-e20586
Author(s):  
Allen Li ◽  
Sanja Dacic ◽  
Timothy Francis Burns ◽  
Mark A. Socinski ◽  
Shira Abberbock ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
High Specificity ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
High Concordance ◽  
Egfr Tkis

e20586 Background: Therapy for NSCLC is based on detection of actionable oncogenic drivers. Conventionally, targetable mutations are detected by tissue biopsy, which may be insufficient for molecular testing. Repeat biopsy is often required at the time of disease progression. Guardant360™ (G360) utilizes digital next-generation sequencing (NGS) to analyze ctDNA in plasma. Limited data exists on clinical outcomes of 3rd generation EGFR tyrosine kinase inhibitors (TKIs) against T790M-mediated resistance detected by digital NGS in ctDNA. We hypothesize that G360 has high concordance in detecting actionable oncogenic drivers and similar clinical outcomes compared with tumor-based genotyping. Methods: G360 (Guardant Health, Inc.) was performed in 20 advanced NSCLC patients (pts) with matched tumor-based genotyping by either Sanger sequencing (N = 10) or Ion Torrent ApliSeq v.2 NGS (N = 10; Life Technologies, Fisher Scientific). Matched genotypes were done at diagnosis (N = 12) or at time of acquired resistance (N = 8). Sensitivity, specificity, and response to EGFR TKIs (RECIST V1.1) were determined. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method. Objective response rates (ORR) were calculated by MedCalc(r) software. Results: Compared with tumor-based testing, G360 has high concordance for EGFR exon 19 deletion, T790M and L858R (90%, 85% and 100%, respectively) and high specificity (100%, 93.3%, and 100%, respectively). OS of pts with T790M or L858R were similar between those detected by G360 and by tumor-based testing (p > 0.99). Pts who received 3rd generation EGFR TKIs (4 osimertinib, 1 PF-06747775) after detected T790M in plasma (N = 4) had similar ORR (50% vs 25% with difference of 25%, 95% CI (-0.45 to 0.75)) and median PFS (7.5 vs 6.0 mos, p = 0.63) as those detected by tumor-based testing (N = 4). Conclusions: G360 showed high concordance for EGFR actionable mutations. Clinical outcomes of 3rd generation EGFR TKI treatment in T790M+ disease were similar between those detected by G360 and those detected by tumor testing. G360 represents a viable option for pts who are not candidates for solid tumor biopsies.

Comparison of fluoropyrimidine based (FP)and taxane based platinum doublets (TP) in frontline treatment of patients with metastatic gastroesophageal adenocarcinomas (mGEAC): A retrospective analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15604-e15604
Author(s):  
Hibah Ismail ◽  
AMR Mohamed ◽  
Yeohan Song ◽  
Nadine Abdallah ◽  
Malini Surapaneni ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Rank Test ◽  
Continuous Variables ◽  
Weighted Estimates ◽  
Significant Difference ◽  
Key Factor ◽  
Frontline Treatment ◽  
Platinum Doublet

e15604 Background: Although, fluoropyrimidine (FP) and taxane based platinum doublet (TP) chemotherapy have demonstrated efficacy against advanced gastroesophageal cancer, these two regimens have not been compared in prospective trials. We retrospectively compared fluoropyrimidine based (FP)and taxane based platinum doublet (TP)chemotherapy in the frontline setting in patients with mGEAC. Methods: Patients with mGEAC treated at Karmanos Cancer Institute between 2000-2014 were reviewed. We compared progression free survival (PFS), Response rate (RR), and toxicity profile of the two regimens. Outcomes were analyzed using weighted estimates. Fisher’s exact tests and Kruskal-Wallis tests were used for categorical and continuous variables, respectively. Survival differences were assessed by a log-rank test. Results: Of the total136 patients, 39% (53) received FP and 61% (83) received TP chemotherapy. Males were 68% (94) of the patients. Gastric, esophageal and gastroesophageal adenocarcinomas contributed to 47% (64), 26.5% (36) and 26.5% (36) of the cases respectively. FOLFOX was the main regimen in FP (62%), followed by 5FU cisplatin (38%). Carboplatin paclitaxel was the main regimen in the TP group. There was no statistically significant difference between the FP and TP arms in terms of PFS, RR, and median OS. The estimated median PFS was 6.39 (95% CI, 5.54-11.15) for the FP group vs 6.92 months (95% CI, 6.13-9.02) for the TP group, (p = 0.90). Objective response rate was (48% for FP group Vs 56% for TP group, p = 0.70). There was more significant grade 4-5 toxicity in FP vs TP based regimen (79 % vs 55 % respectively, p = 0.004). Conclusions: The efficacy of fluoropyrimidine platinum doublet chemotherapy appears to be as comparable to taxane based platinum doublet in the frontline treatment of mGEC. However, the fluorpyrimidine based regimen appears to have more toxicity. Consideration of treatment adverse effects ought to be a key factor in determining the choice of either regimen in mGEAC.

scholarly journals Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

2021 ◽  
Author(s):  
Yang Wang ◽  
Jun Nie ◽  
Ling Dai ◽  
Weiheng Hu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p  = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Efficacy of gefitinib combined with bevacizumab versus gefitinib in advanced EGFR L858R NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21185-e21185
Author(s):  
Xinmin Zhao ◽  
Xianghua Wu ◽  
Huijie Wang ◽  
Hui Yu ◽  
Si Sun ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Therapeutic Option ◽  
Objective Response ◽  
Acquired Resistance ◽  
Response To Treatment ◽  
Control Group ◽  
Special Cases ◽  
Significant Difference ◽  
Experimental Group ◽  
Egfr Tkis

e21185 Background: 60-80% of EGFR+ NSCLC could benefit from the treatment of EGFR TKIs. However, as a result of acquired resistance, median progression-free survival (PFS) associated with EGFR-TKIs monotherapy was rarely longer than 11 months. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) play an important role in the angiogenesis and progression of NSCLC. The combination of EGFR-TKIs and anti-vascular drugs that inhibit the EGFR and VEGF/VEGFR pathways may be a potential therapeutic option for EGFR-mutant NSCLC. The purpose of our study was to evaluate whether gefitinib combined with bevacizumab is associated with an increased PFS benefit compared with gefitinib alone. Methods: This study is a randomized, open-controlled, single-center study. A total of 43 advanced non-squamous NSCLC patients with EGFR L858R mutations were enrolled, including 24 in the experimental group and 19 in the control group. The experimental group received gefitinib combined with bevacizumab (gefitinib 250 mg, QD+bevacizumab 7.5 mg/kg, Q3W), and the control group received gefitinib monotherapy (250 mg, QD). Response to treatment was evaluated after one month of the treatment, followed by once every two months, and adverse events were graded. The primary endpoint was PFS, and secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety and tolerability evaluation. Samples at baseline (tissue or liquid biopsy), 43 days after treatment (liquid biopsy), and disease progression were subjected to genomic (139-gene NGS panel) profiling. Results: As of December 31, 2020, 22 patients were evaluable (12 for experimental group, 10 for control group). The ORR of the experimental group and the control group were 42% vs 60%, respectively, with no significant difference (experimental group: CR = 0, PR = 5, SD = 7, PD = 0; control group: CR = 0, PR = 6, SD = 4, PD = 0). Main adverse reactions included skin rash (n = 16), diarrhea (n = 24), hypertension (n = 2), proteinuria (n = 1). Other special cases developed fever, nausea and vomiting, elevated platelets, conjunctivitis, back pain, which were manageable. 36 patients with baseline liquid biopsy samples can be evaluated (33 plasma and 3 pleural fluid samples). Of these, EGFR L858R were detectable in 86% (n = 31) of patients. The most common co-mutated gene was TP53 (57%), followed by DNMT3A (49%) and TET2 (17%). Mutation profiles were comparable between the two groups. Conclusions: Compared to gefitinib monotherapy, gefitinib combined with bevacizumab in the treatment of non-squamous NSCLC with EGFR L858R showed similar efficacy and safety profiles.

scholarly journals Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang
Keyword(s):  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Deletion Polymorphism ◽  
Asian Populations ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

When will it be better? Lenvatinib combined with TACE for unresectable hepatocellular carcinoma: A retrospective analysis of real-world evidence in China.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 281-281
Author(s):  
Lan Zhang ◽  
Yanhong Wang ◽  
Ningling Ge ◽  
Yu-Hong Gan ◽  
ZhengGang Ren ◽  
...  
Keyword(s):  
Combination Treatment ◽  
Real World ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Optimal Timing ◽  
Real World Data ◽  
Combination Strategy ◽  
Significant Difference

281 Background: TACE and lenvatinib has each shown to prolong overall survival in patients with unresectable HCC, combination of which may also improve clinical outcomes and have been widely used in the real world accordingly. However, the optimal timing of adding on lenvatinb to TACE remains unclear. We are aiming to evaluate the efficacy and safety between two combination strategies. Methods: From Nov 2018 to Jun 2020, 79 consecutive patients had received a combination treatment of lenvatinib and TACE. Patients followed up for more than 2 months were included in this analysis. They were classified as early-combination group(add on lenvatinib before or after the first TACE ) and late-combination group(add on lenvatinib after at least two procedures of TACE ). Tumor response and progression-free survival (PFS,time from the first day of prescribing lenvatinib to progression or death) were assessed according to RECIST1.1 criteria. Liver function were also evaluated at baseline and every 2 months later. AEs were recorded during the combination treatment period according to CTCAE 5.0. Results: A total of 48 u-HCC patients was finally enrolled. Median follow-up in all patients was 9.3(5.3-14.3)months. Patients’ baseline characteristics were similar in two groups. For early-combination group(n=22)and late-combination group(n=26), the mean age was 65±9.7 and 61±11.6years(p=0.2);BCLC stage C HCC was 59% and 54%(p=0.89);and Child-Pugh A proportion was 81.8% and 77%(p=0.73) respectively. The objective response rate(ORR) was 22.9% in total 48 cases. There was no significant difference in response rate (18.2% vs 26.9%, P=0.51) or disease control rate (90.9% vs 92.3%, P=1.00). Median PFS was significantly longer in the early-combination group than that in late-combination group (14.5 vs 8.9 months; p=0.048). The safety profile was similar between two groups. Grade 3/4 adverse events were 3 (13.6%) and 2 cases(7.7%) respectively (P=0.65). Conclusions: This is to date the first real-world data of the combination timing of lenvatinib with TACE in u-HCC patients. Early-combination strategy may be a better option for the u-HCC patients with a longer mPFS.

A phase II, multicenter, randomized, open-label study to evaluate the safety and tolerability of proxalutamide (GT0918) in subjects with metastatic castrate-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 108-108
Author(s):  
Tie Zhou ◽  
Dingwei Ye ◽  
Zhongquan Sun ◽  
Qinggui Meng ◽  
Dalin He ◽  
...  
Keyword(s):  
Dose Level ◽  
Response Rate ◽  
Objective Response ◽  
Specific Antigen ◽  
Stage Iv ◽  
Study Drug ◽  
Progression Free Survival ◽  
Open Label ◽  
Significant Difference ◽  
Psa Progression

108 Background: GT0918 is a 2nd generation of AR antagonist and capability to down-regulate AR level. This study is an open-label, randomized, multicenter, Ph II study to evaluate the safety and efficacy in patients with mCRPC, and to determine the optimal dose for Ph III study. Methods: Patients with historically confirmed mCRPC who progressed after/intolerant to/reluctant to receive Docetaxel and previously treated with abiraterone or enzalutamide were excluded. All the patients received up to 6 cycles or, unacceptable toxicity, or loss of clinical benefit as recommended by PCWG3. Primary endpoint was prostate-specific antigen (PSA) reduction from baseline. Secondary endpoints included time to PSA progression (TTPP), objective response rate (ORR), progression free survival (PFS), disease control rate (DCR) and safety profiles. Results: As of June 30, 2019, 108 treated with GT0918 at three dose levels: 100 mg (n =37), 200 mg (n = 35) and 300 mg (n = 36), the median age of patients was 70.0 years (range 63-77), 88% of patients had stage IV disease at the initial diagnosis and 69.4% had Gleason score ≥ 8. The median duration of disease was 2.88 years. All received prior endocrine therapy, 35.2% received prior chemotherapy, 29.6% received Docetaxel. The median PSA at baseline was 35.285ng/ml, PSA response rate (≥50 % reduction from baseline) was 41.9%. The median time to PSA progression was not reached. There was no significant difference among three arms. Of 19 evaluable patients with target lesions at baseline, the ORR was 15.8% (all were PR) assessed by IRC with RECIST v 1.1, with 20.0% (1/5), 22.2% (2/9), 0 (0/5) at 100, 200, 300 dose level, respectively. The DCR assessed by IRC was 78.9% (CR 0+PR15.8%+SD 63.2%). Of 26 evaluable patients with target lesions at baseline, the ORR was 19.2% assessed by investigators (CR 3.8%+PR 15.4%), with 11.1% (1/9), 20.0% (2/10), 28.6% (2/7) at 100, 200, 300 dose level, respectively. Overall, AEs were experienced by most of patients (94.4 %, n=102). AEs leading to drug interruption were reported in 13 patients (12.0%), 9 (8.3%)of them were suspected to be drug related. AEs leading to discontinuation were reported in 6 patients (5.6%), 3(2.8%) were possibly related to GT0918. 14 patients (13.0%) experienced Grade 3 and 4 AEs. 17 patients (15.7%)experienced SAE, 5(4.6%) of them were suspected to be related to study drug. Most of AEs were mild or moderate. The common suspected AE (≥10%) were asthenia (17.6%, n=19), anemia (14.8%, n=16), AST increased (14.8%, n=16), ALT increased (13.0%, n=14), decreased appetite (13.0%, N=14), white blood cell count decreased (12.0%, n=13), proteinuria (12.0%, n=13). Conclusions: GT0918 showed a manageable safety profile. This study provided preliminary anti-tumor activity in patients with mCRPC. 200mg/day is recommended dose for Ph III trial. Clinical trial information: CTR20170177.

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

Hand–foot syndrome (HFS) as a potential biomarker of efficacy in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib (SU).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 320-320 ◽  
Author(s):  
M. D. Michaelson ◽  
D. P. Cohen ◽  
S. Li ◽  
R. J. Motzer ◽  
B. Escudier ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Time Dependent ◽  
Phase Iii ◽  
Rank Test ◽  
Significant Independent Predictor ◽  
Potential Biomarker

320 Background: HFS and related skin toxicities are common side effects of tyrosine kinase inhibitors such as SU, a multitargeted inhibitor of VEGF and PDGF receptors plus other receptor tyrosine kinases. In a randomized phase III trial of treatment-naïve mRCC pts, SU showed superior progression-free survival (PFS) and objective response rate (ORR) over interferon-alfa, with a median PFS of 11 mo and median overall survival (OS) of 26.4 mo, establishing SU as a reference standard of care (Motzer et al, 2009). In this retrospective analysis, correlations between SU-associated HFS and efficacy endpoints were investigated in mRCC pts from 5 clinical trials in the first- and second-line treatment settings. Methods: Analyses included pooled data from 770 pts who received single-agent SU as 50 mg/d on a 4-week-on/2-week-off schedule (n=544; 71%) or 37.5 mg continuous once-daily dosing (n=226; 29%). Median PFS and OS were estimated by Kaplan–Meier methods and compared between pts with vs without HFS using a log-rank test. ORR was compared by Pearson's chi-square test. Tumor response was assessed by investigators and adverse events were recorded regularly. Multivariate and time-dependent covariate analyses were performed. Results: Of 770 pts, 179 (23%) developed any-grade HFS, compared with 591 (77%) who did not. Most instances of HFS (63%) initially occurred during the first 3 treatment cycles. Pts who developed HFS had significantly better ORR (55.6% vs. 32.7%), PFS (14.3 vs. 8.3 mo), and OS (38.3 vs. 18.9 mo) than pts who did not develop HFS (p<0.0001). In a multivariate analysis, SU-associated HFS remained a significant independent predictor of both PFS and OS (and of OS by time-dependent covariate analysis). Conclusions: In mRCC pts, SU-associated HFS was significantly and independently associated with improved clinical outcomes. Overall, pts who did not develop HFS still had substantial benefit from SU. However, the presence of HFS identified a subset of pts that manifested highly favorable efficacy results with SU. These findings suggest that development of HFS may serve as a predictive biomarker of SU efficacy, although prospective validation is warranted. [Table: see text]

Local ablative therapy (LAT) for oligoprogressive, EGFR-mutant, non-small cell lung cancer (NSCLC) after treatment with osimertinib.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20545-e20545 ◽  
Author(s):  
Chul Kim ◽  
Nitin Roper ◽  
Chuong D. Hoang ◽  
Eva Szabo ◽  
Maureen Connolly ◽  
...  
Keyword(s):  
Disease Progression ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
T790m Mutation ◽  
Tki Treatment ◽  
Egfr Mutant ◽  
A Prospective Study ◽  
Egfr Tki ◽  
Egfr Tkis

e20545 Background: EGFR tyrosine kinase inhibitors (EGFR-TKIs) improve progression-free survival (PFS) in patients with EGFR-mutant NSCLC, but disease progression limits efficacy. Retrospective studies show a survival benefit to LAT in patients with oligoprogressive disease (progression at a limited number of anatomic sites). Methods: This is a prospective study of LAT in patients with oligoprogressive EGFR-mutant NSCLC. Patients with no prior EGFR-TKI therapy (cohort 1) or progression after 1st/2ndgeneration EGFR-TKIs with acquired T790M mutation (cohort 2) receive osimertinib. Upon progression, eligible patients with < = 5 progressing sites undergo LAT and resume osimertinib until disease progression. Patients previously treated with osimertinib qualifying for LAT upon disease progression are also eligible for treatment (cohort 3). Primary endpoint: evaluation of safety and efficacy of reinitiation of osimertinib after LAT (assessed by PFS). Additional goals are assessment of mechanisms of resistance to osimertinib by multi-omics analyses of tumor, blood, and saliva. Results: Between 04/2016 and 01/2017, 15 patients were enrolled (cohort 1: 9, cohort 2: 3, cohort 3: 3). Median age was 57 (range 36-71). Treatment was well tolerated. The most common adverse events (AEs) were rash, diarrhea, thrombocytopenia, and alanine transaminase elevation. Grade 3/4 AEs were observed in 4 (27%) patients. Among evaluable patients, objective response rates prior to LAT in cohorts 1 and 2 were 71% (5/7) and 100% (2/2), respectively, with 6.8 months median PFS (95% CI: 3.4 months-undefined) in cohort 1 and no progressions in cohort 2. To date, 5 patients (33%; cohort 1: 2; cohort 3: 3) had LAT. Two patients with 3 progressing sites underwent a combination of surgery and radiation. Three patients with 1 progressing site underwent surgery alone. Post-LAT PFS and results of molecular analyses will be presented. Conclusions: Patients with EGFR-mutant NSCLC and oligoprogression after EGFR-TKI therapy can be safely treated with LAT. In selected patients, this approach could potentially maximize duration of EGFR-TKI treatment and prevent premature switching to other systemic therapies. Clinical trial information: NCT02759835.

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