An updated analysis of ICOGEN to demonstrate utility of a blood-based proteomic test to predict outcomes in EGFR TKI treated patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20655-e20655
Author(s):  
Yuankai Shi ◽  
Xiaohong Han ◽  
Li Zhang ◽  
Lieming Ding ◽  
Nicholas Dupuis ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Therapeutic Benefit ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Study Endpoint ◽  
Primary Study ◽  
Plasma Samples ◽  
Nsclc Patients ◽  
Test Result

e20655 Background: ICOGEN was a randomized Phase III clinical trial comparing two EGFR tyrosine kinase inhibitors (TKI), icotinib (I) and gefitinib (G), in EGFR gene mutation status unknown non-small-cell lung cancer (NSCLC) patients previously treated with platinum doublet chemotherapy. Plasma samples from study patients were retrospectively analyzed with a commercially-available blood-based proteomic test which has been shown to have prognostic and predictive properties in NSCLC. This study represents an updated analysis of ICOGEN to evaluate the ability of the test to predict outcome based on therapeutic regimen. Methods: Available pre-treatment plasma samples from ICOGEN were retrospectively analyzed with the proteomic test which classifies subjects as Good or Poor. Progression free survival (PFS ) and over-all survival (OS) were analyzed within treatment (TX) arms and test classification. Results: 352 subjects were evaluated, with 277(78.7%) classified as Good and 75(21.3%) classified as Poor. Among all patients evaluated with the proteomic test, the median PFS was 4.9 mo. and 2.3 mo. (HR [95% CI] 0.61 [0.46 – 0.81]; p = 0.0004) and median OS was 16.6 mo. and 5.5 mo. (HR [95% CI] 0.39 [0.29 – 0.50]; p < 0.0001) for the Good and Poor sub-groups, respectively. Association between test result and PFS was significant in patients treated with I (6.0 mo vs. 1.9 mo, HR = 0.43, p < 0.0001), but not significant in patients treated with G (3.7 mo vs. 2.5 mo, HR = 0.85, p = 0.429). Further evaluation demonstrated that the proteomic test predicted differential therapeutic benefit between icotinib and gefitinib for PFS (pint = 0.036). In OS, a significant association between test result and outcome was shown in both the I (16.3 mo vs. 4.0 mo, HR [95% CI] 0.27[0.19-0.39]; p < 0.0001) and G (16.6 mo vs. 7.0 mo, HR [95% CI] 0.51[0.35-0.76; p = 0.0008) arms, which trended towards prediction of differential therapeutic benefit between icotinib and gefitinib for OS (pint = 0.086). Conclusions: For ICOGEN’s primary study endpoint, the proteomic test was predictive of differential therapeutic benefit between icotinib and gefitinib in EGFR mutations status unknown NSCLC patients.

Prospective study for usefulness of circulating-free DNA on prediction of third generation EGFR tyrosine kinase inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21510-e21510
Author(s):  
Hironori Yoshida ◽  
Chiho Nakashima ◽  
Naohisa Matsumoto ◽  
Kentaro Iwanaga ◽  
Noriyuki Ebi ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Disease Progression ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Egfr Tyrosine Kinase ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Nsclc Patients ◽  
Egfr T790m

e21510 Background: Most non-small lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations develop resistance when exposed to EGFR-tyrosine kinase inhibitors (TKIs). T790M develops in about half of patients treated with TKI and can be detected by tumor tissue and cfDNA hotspot tests. However, co-occurring mutations at other loci may impact efficacy. We conducted a prospective, multi-center, observational study to assess the detection rates and predictive values of plasma-based EGFR T790M detection methods for Japanese NSCLC patients treated with osimertinib. Methods: NSCLC patients with tumor EGFR mutations and disease progression after treatment with 1st- or 2nd-generation EGFR-TKI were enrolled. Plasma was collected at the time of clinical disease progression, before osimertinib treatment. The collected plasma was tested for EGFR T90M by in-house plasma MBP-QP and ddPCR assays and compared to clinically tested cobas (Roche) results (including tissue, plasma). The primary endpoint was to demonstrate comparability of our MBP-QP system to cobas using plasma-based EGFR T790M detection to predict the therapeuitic effect of osimertinib via objective response rate (ORR) and disease control rate (DCR). As an exploratory analysis, we used Guardant360 to retrospectively test available banked plasma samples collected describe time points. Results: From Feb 2017 to Jan 2019, 145 patients enrolled. T790M was detected by cobas in 57 cases (44 tissue, 16 plasma, 3 both). ORR and DCR in plasma cobas-positive cases were 62.5% and 81.3%, respectively. MBP-QP found T790M in 9 patients with ORR and DCR 66.7% and 77.8%. ddPCR found 17 cases with ORR and DCR 70.6% and 82.4%. ORR was not correlated to AF. In plasma samples from 54 patients, Guardant360 detected T790M in 57%. Co-occurring alterations such as amplification or minor mutations in EGFR or other genes such as TP53 did not impact ORR, but in the group with poor response to osimertinib, the number of detected gene alterations tended to be large. Two patients with small cell carcinoma transformation had RB1 mutations and MYC amplification. Conclusions: Regardless of the test system, the detection of T790M could predict a good therapeutic effect of osimertinib, but there was no difference in response to osimertinib depending on EGFR T790M AF. Compared to single-gene assessment of EGFR, NGS of cfDNA may be useful for guiding treatment decisions for patients with TKI-resistant NSCLC. Clinical trial information: UMIN000025930.

Disease monitoring and TKI resistance mutations of EGFR mutation-positive NSCLC patients via circulating tumor DNA.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21627-e21627
Author(s):  
Corinna Woestmann ◽  
Christine Ju ◽  
Bernd Hinzmann ◽  
Stephanie J. Yaung ◽  
Michael Thomas ◽  
...  
Keyword(s):  
Disease Progression ◽  
Liquid Biopsy ◽  
Kinase Inhibitors ◽  
Outcome Data ◽  
Egfr Mutations ◽  
Driver Mutations ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
T790m Mutation ◽  
Nsclc Patients

e21627 Background: 15–40% of NSCLC adenocarcinoma patients harbor EGFR sensitizing mutations. Tyrosine kinase inhibitors (TKI) provide significant clinical benefit in this population, yet all patients will develop resistance. Liquid biopsy has been demonstrated to reliably identify tumor associated somatic EGFR mutations. Quantitative assessment of mutated EGFR driven tumors could potentially be used to monitor disease progression, to assess therapeutic response, and to identify resistance mechanisms. Methods: 106 longitudinal plasma samples from 16 NSCLC patients who were treated with osimertinib as either first line or second line therapy were collected. A series of plasma samples collected during treatment and at the time of disease progression were analyzed with the AVENIO ctDNA Surveillance kit*. Mutations at each time point were identified and reported by the AVENIO software v2.0*. The mutation profile of each patient at different timepoints along with the treatment journey was examined in combination with clinical outcome data. Results: EGFR sensitizing mutations were detected in all plasma samples by sequencing except in 3 cases. Patients responsive to anti-EGFR therapy showed a rapid decrease of EGFR driver mutations to non-detectable levels. Meanwhile, patients who had stable disease or rapid disease progression had stable or slightly decreasing ctDNA levels after receiving the treatment. One patient had a MET amplification, FBXL7 SNV, and EGFR T790M detected at the time of disease progression which were not detected at baseline. One patient had both EGFR L858R and T790M mutations. This patient progressed very quickly on erlotinib. Detection of the T790M mutation decreased upon osimertinib administration, however, the L858R mutation level stayed the same. TP53 mutations were elevated in 3 patients at the time of progression, and could potentially be related to anti-EGFR resistance. Conclusions: This study clearly demonstrated that liquid biopsy could identify resistance mutations beyond EGFR prior to clinical progression. Plasma samples collected prior to or at disease progression could facilitate identification of novel resistant mutations to TKI therapy. Further studies to demonstrate the clinical utility of serial blood EGFR testing in NSCLC management are necessary. *For Research Use Only. Not for use in diagnostic procedures.

scholarly journals Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC in Traditionally Unresectable Patients

2021 ◽  
Author(s):  
Ke-Cheng Chen ◽  
Shuenn-Wen Kuo ◽  
Chen-Hao Hsiao ◽  
Jing-Shing Chen
Keyword(s):  
Thoracic Surgery ◽  
Lung Adenocarcinoma ◽  
Surgical Resection ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Multidisciplinary Management ◽  
Advanced Stage ◽  
Nsclc Patients

Abstract IntroductionAdvanced stage non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations may have benefit from tyrosine kinase inhibitors (TKI). However, the role of multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery is uncertain. This study assessed the possible impact of neoadjuvant TKI therapy and thoracic surgery in selected advanced stage patients.MethodsAdvanced stage of IIIB and IVA NSCLC patients were retrospectively reviewed from 2010 to 2013. Patients with EGFR mutations who received neoadjuvant TKI followed by surgical resection were included. All patients were followed up for 5 years or until death.ResultsThere were total 15 advanced stage lung adenocarcinoma patients in the study. 8 patients were stage IIIB and 7 were stage IVA. All tumor sizes significantly decreased after neoadjuvant TKI therapy (p value = 0.0002). 11 patients received adjuvant TKI therapy after surgical resection and others received adjuvant cisplatin-based chemotherapy. Progression-free survival was superior in the group of adjuvant TKI therapy than in the group of adjuvant chemotherapy (median 14 months versus 5.9 months, p value = 0.016). Overall survival (OS) was not different between two groups (p value = 0.755). In the group of adjuvant TKI therapy, median OS in patients harboring exon 19 deletion and exon 21 L858R was 60 months and 44.9 months, respectively (p value = 0.078). ConclusionTKI may decrease the size of EGFR mutation lung adenocarcinoma. A multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery may be discussed in selected advanced stage lung adenocarcinoma.

Phase II study of sorafenib combined with gemcitabine and 5-fluorouracil in patients with metastatic renal cell carcinoma: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16093-e16093
Author(s):  
L. Hongyun ◽  
C. Zhihong ◽  
Y. Xiangqing ◽  
S. Lu ◽  
C. Chuanliang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Kinase Inhibitors ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Eligibility Criteria

e16093 Background: The tyrosine kinase inhibitors sorafenib and sunitinib have been approved for use in patients with advanced RCC and have supplanted immunotherapy as first-line therapy. Nevertheless, complete responses have been observed only rarely with these agents and only 10% of patients experience PR. The vast majority of responding patients will ultimately progress despite continued therapy. In order to improve the objective response rate and the durability of those responses in patients, we conducted a single-institution, single-arm phase II trial of gemcitabine and 5-fluorouracil (5-FU) combined with sorafenib in patients with RCC. Methods: Eligibility criteria included advanced, histologically confirmed RCC; age >18 years; ECOG PS ≤ 2, adequate bone marrow, renal and hepatic function; measurable/evaluable lesions. Gemcitabine was administered at 1,000 mg/m2 over 30 min i.v. on days 1 and 8, followed by 5-FU 400 mg/m2 i.v. bolus on day 1 and 1,200 mg/m2/day × 2 days continuous infusion (28-day cycle). From day 1 of cycle 1, 400 mg sorafenib was continuously given twice daily. The sample size of 21 patients was sufficient to provide 80% power to detect an objective response rate that was greater than 10% with significance that 0.05 level. Results were expressed as mean±SD or median ± 95% CI. The primary study endpoint was objective response rate and the secondary were toxicity, progression-free survival and overall survival. Results: Patients (n = 21) were enrolled from May 2006 to Dec. 2007. The rate of objective response and disease control (including stable disease, complete responses and partial responses) were 38% (95% CI, 18–62%) and 86% (95% CI, 64–97%), respectively. Among them, there is 1 complete response and 2 pts occurred completely liquefaction deliquesce in metastatic lesions. The median PFS time is longer than 13 months, with 6/21 patients remaining progression free at 2008.12.26 the data were compiled for this report (three are longer than 26 months and there other three longer than 13 months ). The median OS time have not yet been reached, because of the amount of censoring data. Conclusions: The combination of sorafenib with gemcitabine and 5-FU shows promising activity for patients with metastatic RCC. No significant financial relationships to disclose.

TGFb expression as predictor of outcome in EGFR wild type (WT) metastatic non-small cell lung cancer (NSCLC) patients (PTS) treated with EGFR tyrosine kinase inhibitors (TKIs).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18104-e18104
Author(s):  
Giovanna Finocchiaro ◽  
Luca Toschi ◽  
Letizia Gianoncelli ◽  
Barbara Canal ◽  
Luca Rubino ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Egfr Mutations ◽  
Study Cohort ◽  
Intrinsic Resistance ◽  
Alk Rearrangement ◽  
Primary Resistance ◽  
Metastatic Nsclc ◽  
Nsclc Patients

e18104 Background: Gefitinib and erlotinib have shown to be highly effective in pts harboring EGFR mutations, while the majority of EGFR wt pts does not respond to treatment.Preclinical data suggested that TGFb and HGF could affect response to TKIs. Aim of the present study is to investigate molecular predictors for primary resistance to TKIs in metastatic NSCLC pts. Methods: This retrospective study included 120 metastatic NSCLC patients treated with gefitinib (68/56.7%) or erlotinib (52/43.3%) in first line (20/16.7%) or after prior chemotherapy (100/83.4%) with at least one measurable lesion and availability of paraffin-embedded tumour tissue from primary cancer. Analyses included presence of mutations in EGFR and KRAS genes, assessment of ALK rearrangement by fluorescence in situ hybridization (FISH) and protein expression of HGF and TGFb by immunohistochemistry (IHC). Pts were grouped in IHC+ and IHC- according to staining intensity. Results: In the whole study cohort response rate (RR) was 9.2%, median progression free survival (PFS) 2.5 months, and overall survival (OS) 7.8 months. EGFR mutations were observed in 9.2% of pts and were significantly associated with better pts outcome. KRAS was mutated in 23.3% of pts without any correlation with clinical end points. ALK translocations were observed in 5 pts (4.2%), and none responded to treatment. IHC was successfully performed for HGF and TGFb in 95 and 75 pts respectively. No difference was seen in HGF+ (9/9.5%) vs HGF- pts in terms of RR, PFS and OS. TGFb+ pts (41/54.7%) had a significantly shorter OS than TGFb- pts (6.7 vs 10.3 months, p=0.020) although no difference in terms of RR and PFS was observed. When restricting survival analysis to EGFR wt/KRAS wt pts (n=80) TGFb+ subjects had a significantly worse PFS (1.9 vs 2.9 months, HR 2.16, CI 95% 1.18;3.95, p=0.013) and OS (5.3 vs 8.8 months, HR 2.07, CI 95% 1.10;3.91, p=0.025) when compared with the TGFb- group. Conclusions: Overexpression of TGFb is associated with a poor outcome in EGFR and KRAS wt pts treated with gefitinb or erlotinib. Prospective validation of the role of TGFb as a mediator of intrinsic resistance to EGFR TKIs in NSCLC is warranted.

Single versus sequential high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ-cell tumors (GCT)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4511-4511 ◽  
Author(s):  
A. Lorch ◽  
O. Rick ◽  
J. T. Hartmann ◽  
C. Kollmannsberger ◽  
B. Metzner ◽  
...  
Keyword(s):  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
High Dose ◽  
Free Survival ◽  
Secondary Endpoints ◽  
One Year

4511 Background: Patients (pts) with relapsed or refractory GCT may be cured by HDCT. It is unknown whether single or sequential HDCT is superior. Methods: Between 11/99 and 11/04, 216 pts with relapsed or refractory GTC were treated in a prospective, randomized, multicenter phase III trial with either one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1500 mg/m2 and etoposide 1500 mg/m2 (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2200 mg/m2, etoposide 1800 mg/m2 and cyclophosphamide 6400 mg/m2 (CEC, arm B) followed by reinfusion of autologous peripheral blood progenitor cells. Primary study endpoint was the event-free survival (EFS) one year after randomization. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. An event was defined as any deviation from the planned treatment, relapse, progression or death from any cause. The planned study size was 230 pts to detect a difference of 15% with an alpha error of 5% and a power of 80%. Results: The study was stopped after recruitment of 216 pts due to excess treatment-related mortality in arm B: 111 pts were randomized in arm A and 105 pts in arm B. Due to non-GCT histologies at review 5/216 pts had to be excluded from further analysis. With a median follow-up of 36 months, 109/211 (52%) evaluable pts are still alive and 91/211 (43%) are progression-free. At one year EFS; PFS and OS are 40%, 55% and 80% in arm A as compared to 37%, 49% and 61% in arm B. Treatment-related deaths mainly due to sepsis and cardiac toxicity were less frequent in arm A (4/111 pts, 4%) as compared to arm B (15/105 pts, 14%) (p = 0.01). Severe non-hematologic organ toxicities were also less frequent in arm A. Conclusions: Treatment with sequential high-dose carboplatin and etoposide is at least as effective but less toxic than single HDCT with carboplatin, etoposide and cyclophosphamide. No significant financial relationships to disclose.

scholarly journals Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients

2021 ◽  
Vol 15 ◽  
pp. 117955492199307
Author(s):  
Klaus Hackner ◽  
Anna Buder ◽  
Maximilian J Hochmair ◽  
Matthaeus Strieder ◽  
Christina Grech ◽  
...  
Keyword(s):  
Stable Disease ◽  
Progressive Disease ◽  
Kinase Inhibitor ◽  
Diagnostic Yield ◽  
Resistance Mutation ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Percent Agreement ◽  
Nsclc Patients ◽  
Egfr Mutated

Background: Proof of the T790M resistance mutation is mandatory if patients with EGFR-mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of EGFR mutations. Methods: Twenty-eight patients with advanced EGFR-mutated NSCLC were included during stable and/or progressive disease. The initial activating EGFR mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR). Results: Activating EGFR mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80. Conclusions: We demonstrated that EGFR mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.

scholarly journals Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tereza Vaclova ◽  
Ursula Grazini ◽  
Lewis Ward ◽  
Daniel O’Neill ◽  
Aleksandra Markovets ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact ◽  
Egfr T790m

AbstractAdvanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M‐positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.

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

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

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

Updated results of European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 1202 cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11518-11518
Author(s):  
Roberta Sanfilippo ◽  
Richard L Hayward ◽  
Jammbe Musoro ◽  
Charlotte Benson ◽  
Michael Gordon Leahy ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Dedifferentiated Liposarcoma ◽  
Study Endpoint ◽  
Primary Study ◽  
Primary Analysis ◽  
European Organization ◽  
Experimental Drugs

11518 Background: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. The most effective agents include doxorubicin, ifosfamide, trabectedin and eribulin, but, in general, objective response rates (ORR) and progression free survival (PFS) are modest. Cabazitaxel exerts its effect through inhibition of microtubular disassembly and has been shown to be relatively safe, effective and well-tolerated. EORTC 1202 assessed whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DD LPS to justify further investigation in a phase III setting. Methods: This was an international multi-center, open label single arm phase II trial. The clinical cut-off date for the primary analysis was performed on August 31, 2020. Data base lock was performed on February 2, 2021. Eligible patients with metastatic or inoperable locally advanced DD LPS, after a centralized pathological review, were treated with cabazitaxel 25mg/m² IV infusion over 1 hour every 21 days. Primary endpoint was PFS rate at 12 weeks assessed by local investigator per RECIST 1.1. Based on a Simon two-stage design, at least 4 out of 17 (Stage 1) and 11 out of 37 (Stage 2) eligible and evaluable patients who are progression-free at 12 weeks were needed. Currently, a centralized radiological assessment is ongoing. Results: Forty patients were registered by 10 institutions in 4 countries between March 2015 and March 2019, with 2 patients being ineligible. One patient was still on treatment at the clinical cut-off date. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. PFS at 12 weeks was 55% (conditional 1-sided 95% CI 40.8-100), achieving the primary study endpoint. The median FU was 21.6 months, median PFS was 6 months and median OS 21 months. RR was 8% with one CR and two PR. Twenty-three(60.5%) pts had a SD. Disease control (PR+SD) was achieved in 26 patients (68%). The most common cabazitaxel -related grade >3 adverse events in all 40 registered patients were Neutrophil count decreased (50%), febrile neutropenia (25%), fatigue (12.5%), and anemia (10%). There were no cabazitaxel-related deaths. Conclusions: EORTC 1202 met its primary endpoint, with 21/38 pts (55%) being progression-free at 12 weeks. Results of this trial confirm activity of cabazitaxel in patients with metastatic or inoperable locally advanced DD LPS and looks interesting if compared to the other available options and experimental drugs recently reported in this patient population. Clinical trial information: NCT01913652.

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