scholarly journals The Real-Life Efficacy And Safety of Osimertinib In Pretreated Advanced Non-Small Cell Lung Cancer Patients With T790M Mutation: A Turkish Oncology Group Study

2021 ◽  
Author(s):  
Mutlu Hizal ◽  
Burak Bilgin ◽  
Nail Paksoy ◽  
Özgür Açıkgöz ◽  
Ahmet Sezer ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Real Life ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
T790m Mutation ◽  
The Real ◽  
Third Line ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation.Materials and Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety.Results: Of 163 patients 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13 months disease follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. Conclusion: Osimertinib is a highly effective option in second or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.

scholarly journals Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

A meta-analysis of comparing EGFR-TKI with chemotherapy as the second-line treatment of NSCLC patients with wild-type EGFR.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19166-e19166 ◽  
Author(s):  
Guanghui Gao ◽  
Shengxiang Ren ◽  
Aiwu Li ◽  
Yayi He ◽  
Xiaoxia Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Overall Response ◽  
Nsclc Patients ◽  
Egfr Tki

e19166 Background: The efficacy of comparing the EGFR-TKI with standard chemotherapy in the second-line treatment of advanced NSCLC with wide-type EGFR were still controversial. To derive a more precise estimation of the two regimens, a meta-analysis was performed. Methods: Medical databases and conference proceedings were searched for randomized controlled trials which compared EGFR-TKI (gefitinib or erlotinib) with standard second-line chemotherapy (docetaxel or pemetrexed) in patients with NSCLC. Endpoints were overall survival, progression-free survival and overall response. Results: Three eligible trials (INTEREST, TITAN and TAILOR) were identified. Lacking for data of overall survival of TAILOR trial, So we only make a preliminary meta-analysis for overall survival. The intention to treatment (ITT) analysis demonstrated that the patients receiving EGFR-TKI had a significantly shorter progression-free survival (PFS) than patients treated with chemotherapy (hazard ratio (HR) = 1.31; 95% confidence intervals (CI) = 1.10-1.56; P = 0.002). The overall survival (OS) and overall response rate (ORR) were coparable between this two groups (HR = 0.96; 95%CI = 0.77-1.19; P = 0.69; relative risk (RR) = 0.37; 95%CI = 0.09-1.54; P = 0.17). Conclusions: Although chemotherapy had a clear superiority in PFS as second-line treatment for patients without EGFR mutations compared with EGFR-TKI, OS and ORR were equal in this two regimens. The toxicity profiles might play an important role in the decision to choose EGFR-TKI or chemotherapy. These findings still need to be verified in larger confirmatory studies in future.

A phase II trial comparing pemetrexed with gefitinib as the second-line treatment of nonsquamous NSCLC patients with wild-type EGFR (CTONG0806).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8042-8042 ◽  
Author(s):  
Jinji Yang ◽  
Ying Cheng ◽  
Mingfang Zhao ◽  
Qing Zhou ◽  
Hong hong Yan ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Free Survival ◽  
Line Setting ◽  
Nsclc Patients

8042 Background: Pemetrexed or gefitinib is one of the standard second-line treatments for advanced non-squamousNSCLC in East Asia. The CTONG 0806 a multi-center, randomized, controlled, open-label phase II trial was designed to explore the efficacy of pemetrexed versus gefitinib as the second-line treatment in advanced NSCLC patients without EGFR mutation. Methods: The patients with locally advanced or metastatic, non-squamous NSCLC previously treated with platinum-based chemotherapy and no EGFR mutation in exons 18-21 were enrolled. Patients were 1:1 randomized to receive either gefitinib 250 mg per oral every day (G arm) or pemetrexed 500 mg/m2 iv day 1 with vitamin B12 and folic acid supplement every 21 days (P arm) until disease progression, unacceptable toxicity, or discontinuation of treatment due to other reason. The primary endpoint was progression-free survival (PFS). The secondary endpoints were 4-month and 6-month progression-free survival rate, overall survival (OS), objective response rate (ORR), quality of life using the FACT-L questionnaire and safety, EGFR and K-ras mutation status were evaluated and correlated with outcomes. Results: From Feb. 2009 to Aug. 2012, 157 evaluable patients were randomized (81 cases in G arm and 76 in P arm). Baseline age, gender, and ECOG performance status were balanced between arms. The primary endpoint of PFS was met with 1.6 months for G arm versus 4.8 months for P arm, the HR is 0.51 (95% CI 0.36~0.73, P<0.001). Overall response rates were 14.7 % and 13.3 % (P=0.814) and DCR were 32.0% and 61.3% (P<0.001) for G arm and P arm, respectively. OS data were not yet mature. More skin rash and diarrhoea were seen in G arm, but more fatigue and ALT increased in P arm. CTCAE grade 3 or 4 of AEs was 12.3% in G arm and 32.9% in P arm (p=0.002). The further analyses of efficacy evaluated by IRR and biomarkers analysis will be presented on the ground. Conclusions: CTONG0806 is the first trial to show significant improvements in PFS and DCR with pemetrexed compared with gefitinib in second-line setting for advanced NSCLC with EGFR wild type. Patients with EGFR wild type did not benefit from EGFR TKI gefitinb in second-line setting. Clinical trial information: NCT00891579.

Lungful: An observational prospective study to assess the molecular epidemiology of EGFR mutations upon progression on or after first line EGFR-TKI therapy, in real-life clinical settings in Greece.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21641-e21641
Author(s):  
Giannis Socrates Mountzios ◽  
Dimitrios Mavroudis ◽  
Epaminondas Samantas ◽  
Anna Koumarianou ◽  
Evangelos Georgios Konstantinos Fergadis ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Second Generation ◽  
Egfr Mutation ◽  
Locally Advanced ◽  
Real Life ◽  
Egfr Mutations ◽  
Liquid Biopsies ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

e21641 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the gold standard 1st line strategy for non-small-cell lung cancer (NSCLC) patients with activating EGFR mutations (EGFRm), associated with improved survival outcomes and quality of life compared to chemotherapy. Despite the high response rate with first- and second- generation TKIs, most patients develop resistance to treatment and progress. The acquisition of T790M mutation in exon 20 is considered the most common resistance mechanism. This study aims to investigate the molecular epidemiology of EGFR resistance mutations, focusing on T790M in EGFRm NSCLC patients treated with TKIs. Methods: The study included patients with locally advanced/metastatic EGFRm NSCLC who have progressed on or after 1st line treatment with first- or second- generation TKI. Samples either from plasma-based liquid biopsy and/or tissue re-biopsy were analysed using the Cobas EGFR Mutation Test v2. All patients signed informed consent and were enrolled between July 2017 and September 2019. Statistical analyses were performed using SAS software, Version 9.4. Results: Ninety-six eligible patients were enrolled. At the time of progression, T790M mutation was detected in 16.7%of the patients using plasma-based liquid biopsies. Among patients with negative T790M result, in plasma, tissue re-biopsy was performed in 22,7% with evaluable/valid results in 72.2% of them. T790M mutation was identified in 38.5% of re-biopsy samples. According to Cobas EGFR Mutation test results (combined plasma and tissue), T790M mutation was identified in 21.9% of the patients. Of T790M-positive patients 42.9% had previously received first and 57.1% second generation EGFR-TKI. Conclusions: Results from this study in real world clinical setting in Greece, show that EGFR-T790M acquired resistance positivity rate in plasma is lower compared to previous reports. Moreover, these data underline the challenges of implementing precision medicine using tissue re-biopsy in advanced/metastatic NSCLC. Clinical trial information: D133FR00126. [Table: see text]

scholarly journals Efficacy and Safety of Docetaxel and Sodium Cantharidinate Combination vs. Either Agent Alone as Second-Line Treatment for Advanced/Metastatic NSCLC With Wild-Type or Unknown EGFR Status: An Open-Label, Randomized Controlled, Prospective, Multi-Center Phase III Trial (Cando-L1)

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Wu ◽  
Chao Deng ◽  
Hui Zhang ◽  
Jie Weng ◽  
Youhua Wu ◽  
...  
Keyword(s):  
Single Agent ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Wild Type ◽  
Open Label ◽  
Metastatic Nsclc ◽  
Significant Difference ◽  
Nsclc Patients

Second-line treatment options for advanced/metastatic non-small cell lung cancer (NSCLC) patients are limited. We aimed to evaluate the efficacy and safety of docetaxel/sodium cantharidinate combination vs. either agent alone as second-line treatment for advanced/metastatic NSCLC patients with wild-type or unknown EGFR status. A randomized, open-label, phase III study was performed at 12 institutions. Patients with failure of first-line platinum regimens were randomized to receive either single-agent sodium cantharivsdinate (SCA) or single-agent docetaxel (DOX) or docetaxel/sodium cantharidinate combination (CON). The primary endpoints were centrally confirmed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. A total of 148 patients were enrolled in our study between October 2016 and March 2020. After a median follow-up time of 8.02 months, no significant difference was observed among the three groups in ORR (SCA vs. DOX vs. CON: 6.00% vs. 8.33% vs. 10.00%, respectively; p=0.814) and DCR (74.00% vs. 52.00% vs. 62.50%, respectively; p=0.080). In additional, the mOS was significantly higher in the CON group, compared with the single-agent groups (7.27 vs. 5.03 vs. 9.83 months, respectively; p=0.035), while no significant differences were observed in terms of PFS (2.7 vs. 2.9 vs. 3.1 months, respectively; p=0.740). There was no significant difference in the baseline QoL scores between the three groups (p&gt;0.05); after treatment, life quality in SCA and CON group was significantly better than that in the DOX group (p&lt;0.05). Furthermore, the incidence of adverse events (AEs) in the SCA group was significantly lower (46.00 vs. 79.17 vs. 25.00%, respectively; p=0.038) and the incidence of grade ≥3 AEs was also significantly lower in the SCA group compared with the DOX and CON groups (10.00 vs. 82.00 vs. 30.00%, respectively; p=0.042). Single-agent SCA and single-agent DOX has similar therapeutic efficacy in the second-line treatment of advanced/metastatic NSCLC with wild-type or unknown EGFR status, but single-agent SCA has fewer AEs and better QoL. Also, SCA plus DOX can significantly improve OS and exerted a significant synergistic effect, with good safety and tolerance profile.

Third-line treatment: A randomized, double-blind, placebo-controlled phase III ALTER-0303 study—Efficacy and safety of anlotinib treatment in patients with refractory advanced NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9053-9053 ◽  
Author(s):  
Baihui Han ◽  
Kai Li ◽  
Qiming Wang ◽  
Yizhuo Zhao ◽  
Li Zhang ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Advanced Nsclc ◽  
Phase Iii ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Third Line ◽  
Ecog Ps ◽  
Third Line Treatment

9053 Background: Anlotinib hydrochloride, an oral TKI targeting VEGFR, FGFR, PDGFR and c-Kit, showed promising efficacy in PhaseⅡstudy. Here, we evaluated the efficacy and safety of anlotinib as third-line treatment for advanced NSCLC, a randomized, double-blind, placebo-controlled Phase Ⅲtrial (ALTER-0303). Methods: Eligible ⅢB/Ⅳ NSCLC pts who progressed after at least 2 lines of prior therapies were randomized 2:1 to receive anlotinib or placebo (12 mg QD from day 1 to 14 of a 21-day cycle) till progression or intolerable toxicity. Enrolled pts harboring EGFR or ALK mutations must had failed in previous match-targeted therapies. The primary endpoint is OS; secondary endpoint includes PFS, DCR and ORR. Results: As of Aug 2016, total of 437 pts from 31 sites were randomized. The baseline characteristics of Anlotinib arm (N=294) and placebo arm (N=143) were well balanced in the age, gender, ECOG PS and gene states. With 292 OS events (66.82%), significant superiorities in OS, PFS, DCR and ORR were observed in Anlotinib arm according to investigator-assessed results. Grade ≥ 3 treatment-related AEs were hypertension, dermal toxicity and hypertriglyceridemia. There was no treatment–related death in either arm. (Data presented in the Table.) Conclusions: ALTER-0303 trial met its primary endpoint. Anlotinib significantly improved OS and PFS in advanced NSCLC with a manageable safety profile. The results strongly suggest that anlotinib should be considered as a candidate for the third-line treatment or beyond in advanced NSCLC. Clinical trial information: NCT02388919. [Table: see text]

The efficacy and safety profile of anlotinib plus docetaxel as second-line treatment in advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21068-e21068
Author(s):  
Zhiqiao Xu ◽  
Yan Zhang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Small Cell Lung

e21068 Background: Docetaxel is a standard second line treatment in advanced NSCLC, but the treatment effect is limited. Previous studies, such as REVEL, demonstrated that anti angiogenic therapy combined with docetaxel had significantly therapeutic efficacy. Anlotinib is an oral multi target angiogenesis TKI targeting the VEGFR, FGFR, PDGFR and c Kit. The ALTER 0303 trial showed that anlotinib improved both PFS and OS in later-line treatment for advanced NSCLC, and this study aims to investigate the efficacy and safety of Anlotinib combined with docetaxel in second-line treatment in advanced non-small cell lung cancer (NSCLC). Methods: This is a single-center, single-arm clinical trial. A group of 30 patients of histologically or cytologically confirmed, locally advanced stage IIIB-IV NSCLC and with ECOG PS 0-1 were admitted to the Kaifeng Central Hospital Cancer Center. Patients who progressed after first-line treatment were treated with anlotinib (12 mg p.o., QD d1 to 14, q3w) combined with docetaxel (75mg/m2, iv, QD, d1 to 14, q3w) as the second-line therapy. The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 30 patients were enrolled from October 2018 to April 2020. At data cutoff (Sept. 30, 2020), 30 patients were available for efficacy analysis. The median progression-free survival (mPFS) was 7.5 months (2.0-18.5). Among these patients, there was 1 CR, 9 PR, 15 SD, 5 PD, resulting in the ORR = 33.33% and the DCR = 83.33%. The Cox multivariate analysis showed that stage is an independent risk factor affecting prognosis ( p= 0.003). The most common grade 3 AEs were leukopenia (23,3%), neutropenia (13.3%), hypertension (13.3%), which can be controlled, and no grade 4 or grade 5 AEs occurred. Conclusions: Second line anlotinib plus docetaxel showed clinical benefit in advanced NSCLC patients in terms of PFS, ORR and DCR, and the incidence of adverse reactions are tolerable. This combination might be a promising option for patients advanced NSCLC.

The efficacy and safety of EGFR-TKI combined with chemotherapy in NSCLC patients with EGFR co-mutation with other oncogenic alterations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21077-e21077
Author(s):  
Wenhua Zhao ◽  
Wei Jiang ◽  
Hongtu Qiu ◽  
Aiping Zeng ◽  
Xiangqun Song ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Monotherapy Group ◽  
Efficacy And Safety ◽  
Observation Study ◽  
Primary Resistance ◽  
Nsclc Patients ◽  
Egfr Tki

e21077 Background: Previous studies indicated primary resistance to EGFR-TKIs might occur in EGFR co-mutation with other oncogenic alterations. However, the optimal therapeutic regimen for advanced NSCLC with EGFR co-mutation was still unknown. This respective observation study aimed to assess the efficacy and safety of the combination therapy with EGFR-TKI and chemotherapy in this sub-population. Methods: In this retrospectively study, from March 2017 to November 2019 advanced NSCLC patients with EGFR mutation detected using next-generation sequencing targeting 59 genes were screened for eligibility. We included patients of EGFR co-mutation with other oncogenic alterations receiving EGFR-TKI monotherapy or TKI plus chemotherapy as first-line therapy. The primary outcome was objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Disease control rate (DCR) and safety profile were considered to be the secondary endpoints. Results: Total 48 patients were enrolled. Among patients with concomitant mutation, the combination of chemotherapy with TKI was found to prolong mPFS (12.5 vs 7.3 months; HR, 0.38; 95%CI: 0.17-0.81; P = 0.012) compared with TKI monotherapy, with a trend of longer mOS (27.0 vs 22.4 months; HR, 0.40; 95%CI: 0.15-1.05; P = 0.062) and higher ORR (68.4% vs 44.8%, P = 0.113). The DCR were 100% in combination group and 93.1% in monotherapy group (P = 0.99). A proportion of 13.8% patients reported grade≥3 treatment-related adverse events in monotherapy group and 36.8% in combination group. Conclusions: EGFR co-mutation with other oncogenic alterations associated with poor treatment outcome with EGFR-TKI monotherapy. The combination of EGFR-TKI and chemotherapy was effective in this sub-population and side-effects were tolerable. The outcomes of this study should be confirmed by prospective clinical trials in future.

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