scholarly journals ALK Resistance Mutations and Efficacy of Lorlatinib in Advanced Anaplastic Lymphoma Kinase-Positive Non–Small-Cell Lung Cancer

2019 ◽  
Vol 37 (16) ◽  
pp. 1370-1379 ◽  
Author(s):  
Alice T. Shaw ◽  
Benjamin J. Solomon ◽  
Benjamin Besse ◽  
Todd M. Bauer ◽  
Chia-Chi Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Second Generation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Resistance Mutations ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

PURPOSE Lorlatinib is a potent, brain-penetrant, third-generation anaplastic lymphoma kinase (ALK)/ROS1 tyrosine kinase inhibitor (TKI) with robust clinical activity in advanced ALK-positive non–small-cell lung cancer, including in patients who have failed prior ALK TKIs. Molecular determinants of response to lorlatinib have not been established, but preclinical data suggest that ALK resistance mutations may represent a biomarker of response in previously treated patients. PATIENTS AND METHODS Baseline plasma and tumor tissue samples were collected from 198 patients with ALK-positive non–small-cell lung cancer from the registrational phase II study of lorlatinib. We analyzed plasma DNA for ALK mutations using Guardant360. Tumor tissue DNA was analyzed using an ALK mutation–focused next-generation sequencing assay. Objective response rate, duration of response, and progression-free survival were evaluated according to ALK mutation status. RESULTS Approximately one quarter of patients had ALK mutations detected by plasma or tissue genotyping. In patients with crizotinib-resistant disease, the efficacy of lorlatinib was comparable among patients with and without ALK mutations using plasma or tissue genotyping. In contrast, in patients who had failed 1 or more second-generation ALK TKIs, objective response rate was higher among patients with ALK mutations (62% v 32% [plasma]; 69% v 27% [tissue]). Progression-free survival was similar in patients with and without ALK mutations on the basis of plasma genotyping (median, 7.3 months v 5.5 months; hazard ratio, 0.81) but significantly longer in patients with ALK mutations identified by tissue genotyping (median, 11.0 months v 5.4 months; hazard ratio, 0.47). CONCLUSION In patients who have failed 1 or more second-generation ALK TKIs, lorlatinib shows greater efficacy in patients with ALK mutations compared with patients without ALK mutations. Tumor genotyping for ALK mutations after failure of a second-generation TKI may identify patients who are more likely to derive clinical benefit from lorlatinib.

scholarly journals Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Jin Kang ◽  
Xu-Chao Zhang ◽  
Hua-Jun Chen ◽  
Wen-Zhao Zhong ◽  
Yang Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Fusion Partner ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

BackgroundEchinoderm microtubule-associated protein-like 4 (EML4) is the canonical anaplastic lymphoma kinase (ALK) fusion partner in non-small cell lung cancer (NSCLC), and ALK-positive patients showed promising responses to ALK tyrosine kinase inhibitors (TKIs). However, studies that comprehensively investigate ALK TKI treatment in patients with different ALK fusion patterns are still lacking.MethodsNinety-eight ALK-positive patients with advanced NSCLC were retrospectively studied for their response to crizotinib and subsequent treatments. Comprehensive genomic profiling (CGP) was conducted to divide patients into different groups based on their ALK fusion patterns. Non-canonical ALK fusions were validated using RNA-sequencing.Results54.1% of patients had pure canonical EML4-ALK fusions, 19.4% carried only non-canonical ALK fusions, and 26.5% harbored complex ALK fusions with coexisting canonical and non-canonical ALK fusions. The objective response rate and median progression-free survival to crizotinib treatment tended to be better in the complex ALK fusion group. Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical EML4-ALK fusion group (p = 0.010). The complex ALK fusion group also tended to respond better to next-generation ALK TKIs, which were used as later-line therapies. Most identified non-canonical ALK fusions were likely to be expressed in tumors, and some of them formed canonical EML4-ALK transcripts during mRNA maturation.ConclusionOur results suggest NSCLC patients with complex ALK fusions could potentially have better treatment outcomes to ALK TKIs therapy. Also, diagnosis using CGP is of great value to identify novel ALK fusions and predict prognosis.

scholarly journals Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program

2021 ◽  
Vol 13 ◽  
pp. 175883592110196
Author(s):  
Oliver Illini ◽  
Maximilian Johannes Hochmair ◽  
Hannah Fabikan ◽  
Christoph Weinlinger ◽  
Amanda Tufman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Real World Setting ◽  
Access Program

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38–89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1–8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53–81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8–22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.

scholarly journals The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab

2021 ◽  
Vol 10 (5) ◽  
pp. 1005
Author(s):  
Edoardo Lenci ◽  
Luca Cantini ◽  
Federica Pecci ◽  
Valeria Cognigni ◽  
Veronica Agostinelli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Serum Albumin ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Albumin Concentration ◽  
Small Cell Lung ◽  
First Line

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 − GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. Conclusion: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.

The effect and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer

2019 ◽  
Vol 49 (8) ◽  
pp. 762-765 ◽  
Author(s):  
Hiromi Watanabe ◽  
Toshio Kubo ◽  
Kiichiro Ninomiya ◽  
Kenichiro Kudo ◽  
Daisuke Minami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Careful Consideration ◽  
Small Cell ◽  
Small Cell Lung

Abstract Introduction Immune checkpoint inhibitors (ICIs) have demonstrated long survival for the treatment of advanced non-small cell lung cancer (NSCLC). However, the effect and safety of ICI rechallenge have not been fully evaluated. The aim of this study was to investigate the efficacy and safety of ICI rechallenge in NSCLC patients. Methods We defined ‘rechallenge’ as re-administration of ICIs for patients who were previously treated with ICIs and discontinued treatment for any reason, and received subsequent chemotherapy. We retrospectively analyzed the histories of 434 patients with advanced NSCLC who received ICIs from December 2015 to December 2017 at seven centers. Results A total of 317 patients discontinued the ICI treatment, and 14 patients (4.4%) received ICI rechallenge. All 14 patients discontinued the first ICI due to disease progression. Eight patients received the same kind of ICIs, and six patients received different ICIs. Median progression-free survival and overall survival were 1.5 months [95% confidence interval (CI): 0.8–2.6] and 6.5 months [95% CI: 1.4–19.0], respectively. The objective response rate was 7.1%, and the disease control rate was 21.4%. Two of three patients who achieved at least a stable disease, received radiotherapy between the first and second ICIs. Adverse events were not significantly different compared with the first ICIs. Conclusions In this study, the effect of ICI rechallenge was limited. Careful consideration of the administration of ICI rechallenge is necessary. This report involved a small number of cases, so further large prospective studies are warranted to confirm the efficacy of ICI rechallenge and to investigate predictive markers to identify a patient population in which ICI rechallenge is effective.

scholarly journals Brigatinib vs Alectinib in Crizotinib-Resistant Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer (ALTA-3)

2021 ◽  
Author(s):  
Sanjay Popat ◽  
Geoffrey Liu ◽  
Shun Lu ◽  
Gregory Song ◽  
Xin Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
End Point

Crizotinib is highly efficacious and more tolerable than chemotherapy for ALK+ non-small-cell lung cancer (NSCLC), but its progression-free survival benefit and intracranial efficacy have limitations. Head-to-head comparisons of next-generation ALK inhibitors in patients with ALK+ NSCLC progressing on crizotinib will contribute toward optimizing survival. This international, Phase III, randomized, open-label study (ALTA-3) will therefore assign patients with locally advanced or metastatic ALK+ NSCLC progressing on crizotinib to receive either brigatinib 180 mg qd (7-day lead-in at 90 mg qd) or alectinib 600 mg twice daily. The primary end point is progression-free survival as assessed by a blinded Independent Review Committee; the key secondary end point is overall survival. Trial registration number: NCT03596866  (ClinicalTrials.gov)

scholarly journals Phase II trial of S-1 plus cisplatin combined with bevacizumab for advanced non-squamous non-small cell lung cancer (TCOG LC-1202)

2019 ◽  
Vol 49 (8) ◽  
pp. 749-754
Author(s):  
Akihiko Miyanaga ◽  
Kaoru Kubota ◽  
Yukio Hosomi ◽  
Yusuke Okuma ◽  
Koichi Minato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Endpoint ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Standard Chemotherapy Regimen ◽  
Grade 3

Abstract Background S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). The addition of bevacizumab has been shown to significantly improve overall survival (OS) in patients with advanced non-squamous (NSq) NSCLC who received carboplatin plus paclitaxel, however, failed to show an OS advantage in patients who received cisplatin plus gemcitabine. Methods Chemotherapy-naive patients with Stage IIIB, IV or recurrent non-SQ NSCLC were treated with a 3-week cycle of S-1 80 mg/m2 on days 1–14, cisplatin 60 mg/m2 on day 8 and bevacizumab 15 mg/kg on day 8 for 4–6 cycles. Patients without progressive disease (PD) received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 80 mg/m2 every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile and Quality of life (QOL). Results From June 2013 to January 2015, 39 eligible patients were enrolled from eight institutions. Thirty-one patients (79%) completed four cycles of induction chemotherapy, and maintenance chemotherapy was initiated in 23 patients (59%). Median PFS, OS and ORR were 7.3 months (95% CI: 5.9–8.7), 21.4 months (95% CI: 14.7—not reached) and 64%, respectively. The most common grade 3/4 toxicities were leukopenia (12.8%), neutropenia (23.0%) and hypertension (28.2%). QOL analyses showed detrimental effects after initiation of the regimen. Conclusions S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced NSq-NSCLC. RR was anticipated to be high with acceptable toxicities.

Efficacy of platinum-pemetrexed combination chemotherapy in ALK+ non-small cell lung cancer refractory to second-generation ALK TKIs.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9067-9067
Author(s):  
Jessica Jiyeong Lin ◽  
Adam Jacob Schoenfeld ◽  
Viola Weijia Zhu ◽  
Beow Y. Yeap ◽  
Emily Chin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Second Generation ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Entire Cohort ◽  
Treatment Naïve

9067 Background: Second-generation (gen) ALK tyrosine kinase inhibitors (TKIs) are standard first- and second-line therapies in patients (pts) with advanced ALK+ non-small cell lung cancer (NSCLC). After progression on second-gen TKI(s), standard options include platinum (PT)-based chemotherapy (chemo) or the third-gen ALK TKI lorlatinib. The efficacy of PT-based chemo is established in treatment-naive pts but is undefined in pts who have failed prior ALK TKIs. Here we evaluate the efficacy of PT/pemetrexed (pem)-based chemo in pts with ALK+ NSCLC refractory to second-gen TKIs. Methods: A retrospective study was performed at three institutions. Pts were eligible if they had advanced ALK+ NSCLC refractory to ≥1 second-gen TKI, and received PT-pem-based chemo. Medical records and imaging were reviewed to determine outcomes. Results: Among 55 eligible pts, chemo regimens included: PT/pem (31/55, 56%), PT/pem/bevacizumab (bev) (6/55, 11%), PT/pem/PD-1 inhibitor (3/55, 5%), PT/pem with ALK TKI (8/55, 15%), PT/pem/bev with TKI (6/55, 11%), and PT/pem/PD-1 inhibitor with TKI (1/55, 2%). Pts had received one (6/55, 11%), two (38/55, 69%), or more (11/55, 20%) prior TKIs. Six pts (11%) previously received adjuvant or neoadjuvant chemo. Radiographic data for response evaluation was available for 39 pts. Among 36 pts with measurable baseline disease, confirmed ORR was 31% (11/36; 95% CI, 16-48%); 13 (36%) had stable disease. The median duration of response was 5.4 months (95% CI, 1.5-7.1 months). The median progression-free survival (PFS) for the entire cohort was 4.0 months (95% CI, 2.8-4.6 months). Chemo (PT/pem +/- bev or PD-1 inhibitor) plus ALK TKI (n = 15) was associated with a significant increase in PFS compared to chemo without TKI (n = 40) (median PFS 6.8 vs 3.2 months; HR 0.306; p = 0.002). Similarly, PT/pem plus ALK TKI (n = 8) was associated with increased PFS compared to PT/pem without TKI (n = 31) (median PFS 6.8 vs 2.9 months; HR 0.358; p = 0.036). Conclusions: The efficacy of PT-pem-based chemo is limited after failure of second-gen ALK TKIs but may be higher in pts who receive chemo plus ALK TKI, suggesting a potential role for ongoing ALK inhibition. The modest benefit of PT-pem-based chemo highlights the need for other therapeutic strategies for pts refractory to second-gen TKIs.

Randomized phase Ⅱ trial of uracil/tegafur and cisplatin versus pemetrexed and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage Ⅲ non-squamous non-small-cell lung cancer: NJLCG1001.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8527-8527
Author(s):  
Kana Watanabe ◽  
Yukihiro Toi ◽  
Atsushi Nakamura ◽  
Tatsuro Fukuhara ◽  
Ryosuke Chiba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Involved Field

8527 Background: It is unknown which regimen is the best in concurrent chemoradiotherapy (CCRT) of locally advanced non-squamous non-small cell lung cancer (NSCLC). Our previous randomized phase Ⅱ study, NJLCG0601, showed that chemoradiotherapy with uracil/tegafur (UFT) and cisplatin achieved promising efficacy with acceptable toxicities. In this trial, this regimen was compared to a regimen with pemetrexed and cisplatin for stage Ⅲ non-squamous NSCLC. Methods: Patients with inoperable stage Ⅲ non-squamous NSCLC were randomized to UFT 400 mg/m2 on days 1–14 and 29–42, and cisplatin 80 mg/m2 on days 8 and 36 (UP), or pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on days 1, 22, and 43 (PP). Involved-field radiotherapy (IFRT) was administered from day 1 to a total dose of 66 Gy radiotherapy in 33 fractions. Consolidation chemotherapy after CCRT was not planned for this study. The primary endpoint was 2-year overall survival (OS), with expected rates of 55% and a lower limit of 35% (alfa 0.05, beta 0.2). Secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), OS, and toxicity profile. Results: From November 2010 to June 2017, 86 patients were enrolled from 11 institutions. Of the 85 eligible patients, the rate of 2-year OS was 78.6% (95% CI: 62.8–88.3%) in the UP arm and 85.5% (95% CI: 70.5–93.2%) in the PP arm. The ORR was 76.7% in the UP arm and 81.0% in the PP arm. With a median follow-up of 54 months, median PFS and OS were 12.3 and 64.2 months in the UP arm, and 26.2 months and not reached in the PP arm, respectively. Grade 3/4 febrile neutropenia was more frequent in the UP arm than in the PP arm (14.0%, 2.0%, respectively). Grade 3/4 pneumonitis occurred in 7.0% and 4.8% of patients in UP and PP arms, respectively. Conclusions: Both regimens with IFRT achieved the expected 2-year survival rate. PP had more favorable results than UP in terms of OS and PFS. We selected the PP arm for the next step.

scholarly journals Atezolizumab Plus Chemotherapy Vs Chemotherapy Alone for Non-small Cell Lung Cancer: A Meta-analysis of Different PD-L1-expression Levels

2020 ◽  
Author(s):  
Zhang Hong ◽  
Zhong Xiaoyu ◽  
Liu Zhaowei ◽  
Miao Feifei ◽  
Zhang Changgeng
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Double Blind ◽  
Grade 3

Abstract Background Atezolizumab was effective and well tolerated in pretreated non-small-cell lung cancer (NSCLC). This meta-analysis assessed that the efficacy and safety of atezolizumab plus chemotherapy combination, compared to chemotherapy alone.Methods This meta-analysis included double-blind randomized controlled trials (RCTs) comparing atezolizumab plus chemotherapy combination with chemotherapy alone for NSCLC. The subgroups were the high expression of PD-L1（PD-L1-high）, the low expression of PD-L1 （PD-L1-low） and the negative expression of PD-L1 (PD-L1-negative). The hazard ratios (HRs) and odds ratios (ORs) with 95% confidence interval (CI) were calculated. The outcome parameters were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events Grade 3-5（AEs G3-5）.Results A total of 6 articles were included in this meta-analysis. The results indicated that atezolizumab plus chemotherapy combination had better efficacy than chemotherapy alone for PFS (HR=0.64, 95% CI=0.60 to 0.70,P<0.001), PFS（PD-L1-high）(HR=0.41, 95% CI=0.34 to 0.51,P<0.001), PFS（PD-L1-low）(HR=0.63,95% CI 0.55 to 0.72,P<0.001) and PFS（PD-L1-negative）(HR=0.71, 95% CI=0.61 to 0.83,P<0.001). There were statistically significant improvements in terms of OS (HR = 0.79, 95% CI = 0.73 to 0.86,P<0.001) 、OS (PD-L1-high) (HR = 0.65, 95% CI = 0.48 to 0.88,P<0.01) and OS (PD-L1-negative) (HR = 0.84, 95% CI = 0.72 to 0.98,P<0.05). Significant benefits were observed in ORR (OR=1.81,95% CI=1.58 to 2.08, P<0.001), ORR（PD-L1-high）(OR=2.24,95% CI=1.24 to 4.06,P<0.01), ORR（PD-L1-low）(OR=1.51,95% CI=1.03 to 2.21,P<0.05) and ORR（PD-L1-negative）(OR=1.54,95% CI=1.05 to 2.27,P<0.05). Meanwhile, atezolizumab was well tolerated and the incidence of AEs G3-5 (OR = 1.32, 95% CI = 1.06 to 1.64,P=0.01). Conclusion The atezolizumab plus chemotherapy combination had excellent efficacy and great safety than chemotherapy alone for NSCLC. Furthermore, these benefits had nothing to do with the state of PD-L1 expression.

scholarly journals Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20626-e20626 ◽  
Author(s):  
Si-Yu Wang ◽  
Zui Liu ◽  
Wei Ou ◽  
Ning Li ◽  
Hui-qi Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Squamous Carcinoma ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Anaplastic Lymphoma

e20626 Background: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), has been proved to be effective and safe in treating patients with advanced gastric cancer who failed to second-line chemotherapy. As the VEGFR-2 targeted therapy has made encouraging progress in the treatment of a broad range of malignancies, we aimed to explore the efficacy and safety of apatinib in treatment of advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Methods: In this open-label single-arm, phase II study, patients were treated with apatinib alone in daily dose of 250 mg, po, in the second- or third-line setting. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Results: From January 28, 2016 to December 31, 2016, 33 patients were enrolled, including 9 patients with squamous carcinoma and 24 patients with adenocarcinoma. Fourteen patients were detected as EGFR mutations and all the cases have no anaplastic lymphoma kinase (ALK) fusion gene. The median progression free survival (mPFS) of the whole group was 4.0 (95% confidence interval [CI], 0-8.2) months, while the mPFS of adenocarcinoma was 4.0 (95% CI, 2.1-5.9) months and the mPFS of squamous carcinoma was 5.5 (95% CI, 0-13.9) months (P = 0.245). Among the 33 patients, partial response was noted in 3 patients (9.09 %) and stable disease in 14 (42.42%). The disease control rate (DCR) was 51.52%. The common side effects of apatinib were hypertension, hand-foot syndrome and proteinuria, which accounted for 33.33%, 24.24%, and 15.15%, and no grade 3/4 adverse reactions occurred. The toxicity of apatinib was controllable and tolerable. Conclusions: Apatinib appears to be effective and safe for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Prospective studies are needed for further investigation.

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