Prediction models for platinum-based chemotherapy response and toxicity in advanced NSCLC patients

Background.Osteopontin (OPN) is associated with prognosis of patients with non-small-cell lung cancer (NSCLC). However, little is known about the association between OPN gene polymorphism and the chemotherapy response in NSCLC patients.Methods.A total of 497 patients with inoperable advanced stage of NSCLC (stages III B and IV NSCLC) were enrolled. All patients had received platinum-based chemotherapy. OPN gene polymorphisms at 156 GG/G, 443 C/T, and −66T/G were determined.Results.The genotypes and allele frequency of −443C>T were significantly different between the responders and nonresponders. Responders had a markedly higher frequency of −443TT genotype than responders (40.71% versus 19.09%,P<0.001). With CC as reference, the TT genotype carriers had a higher chance to be well responders (adjustedOR=4.43, 95% CI: 2.60–7.53, adjustedP<0.001). The median overall survival time for patients with −443CC, −443CT, and −443TT genotype carriers was significantly different. Multivariate Cox proportional hazards regression models showed that OPN −443C>T gene polymorphisms were closely correlated to poor NSCLC prognosis.Conclusion.OPN −443C>T gene polymorphism may be used as a molecular marker to predict the treatment response to chemotherapy in advanced NSCLC patients.

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BMP-4 Genetic Variants and Protein Expression Are Associated with Platinum-Based Chemotherapy Response and Prognosis in NSCLC

BioMed Research International ◽

10.1155/2014/801640 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Sun Xian ◽

Lang Jilu ◽

Tian Zhennan ◽

Zhou Yang ◽

Hu Yang ◽

...

Keyword(s):

Genetic Variants ◽

Advanced Nsclc ◽

Nonsmall Cell Lung Cancer ◽

Tissue Expression ◽

Chemotherapy Response ◽

Potential Predictor ◽

Bone Morphogenic Proteins ◽

Platinum Based Chemotherapy ◽

Nsclc Patients

To explore the role of genetic polymorphisms of bone morphogenic proteins 4 (BMP-4) in the response to platinum-based chemotherapy and the clinical outcome in patients with advanced nonsmall cell lung cancer (NSCLC), 938 patients with stage III (A+B) or IV NSCLC were enrolled in this study. We found that the variant genotypes of 6007C > T polymorphisms significantly associated with the chemotherapy response. The 6007CC genotype carriers had a higher chance to be responder to chemotherapy (adjusted odd ratio = 2.77; 95% CI: 1.83–4.18; adjusted < 0.001). The 6007C > T polymorphisms and BMP-4 expression also affect the prognosis of NSCLC. Patients with high BMP-4 expression had a significantly higher chance to be resistant to chemotherapy than those with low BMP-4 expression (OR = 2.81; 95% CI: 1.23–6.44;P=0.01). The hazard ratio (HR) for 6007TT was 2.37 times higher than 6007CC (P=0.003). In summary, the 6007C > T polymorphism of BMP-4 gene and BMP-4 tissue expression may be used as potential predictor for the chemotherapy response and prognosis of advanced NSCLC.

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RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced NSCLC patients treated with cisplatin-based chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8097 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8097-8097

Author(s):

C. Zhou ◽

S. Zhou ◽

L. Zhang

Keyword(s):

Clinical Outcome ◽

Mrna Expression ◽

Advanced Nsclc ◽

Response Rate ◽

Stage Iiib ◽

Expression Levels ◽

Platinum Based Chemotherapy ◽

Brca1 Mrna ◽

Nsclc Patients ◽

Mrna Expression Levels

8097 Background: Platinum-based chemotherapy is the standard treatment for advanced NSCLC patients. RRM1 and BRCA1 are important regulators of chemosensitivity of NSCLC. Methods: Stage IIIb/IV NSCLC patients were given cisplatin-based chemotherapy based upon expression levels of RRM1 and BRCA1 mRNA in the tumor. Expression levels of the two genes were determined by real-time PCR and cut-off points were reported in our previous study. The patients with low expression of RRM1 were treated with gemcitabine/cisplatin up to 4 cycles. The others were treated with vinorelbine or paclitaxel plus cisplatin up to 4 cycles. After the chemotherapy, the patients were followed every 6 weeks up to disease progression and then every 3 months up to death. Results: 90 chemonaive, stage IIIB/IV, PS 0–1 NSCLC patients were enrolled. Age 60 (40–78) yrs old, male/female: 73/27%; adenocarcinoma/squamous/adeno-squamous/undefined NSCLC: 49/33/11/7%;,stage IIIb/IV: 13/87%. Overall response rate was 41.1%, stable disease 42.2%, progressive disease 16.7%. Disease was not progressive in 33 patients. Median TTP was 5 months. Response rate and TTP were better in those with low RRM1 expression ( Table ). Toxicity of the chemotherapy was acceptable. Overall survival will be reported in the conference. Conclusions: RRM1 and BRCA1 mRNA expression levels in non-small cell lung cancer are associated with clinical outcome to cisplatin-based chemotherapy. Prospective studies are ongoing to evaluate the role of the two genes in tailoring chemotherapy in our center. [Table: see text] No significant financial relationships to disclose.

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Randomized phase III trial of gemcitabine and cisplatin versus gemcitabine alone in patients with advanced non-small cell lung cancer (NSCLC) and a performance status (PS) 2: CAPPA-2 study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8066 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8066-8066

Author(s):

Alessandro Morabito ◽

Vittorio Gebbia ◽

Saverio Cinieri ◽

Maria Grazia Viganò ◽

Roberto Bianco ◽

...

Keyword(s):

Advanced Nsclc ◽

Performance Status ◽

Single Agent ◽

Stage Iv ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Platinum Based Chemotherapy ◽

Nsclc Patients ◽

First Line Treatment

8066 Background: Platinum-based chemotherapy (CT) is the standard treatment for patients (pts) with advanced NSCLC, but the evidence of its efficacy among ECOG PS2 pts is weak, because these pts are usually excluded from clinical trials; concern exists about tolerability and feasibility of standard CT in these pts. No prospective randomized trial has tested the addition of cisplatin to single-agent CT in pts with advanced NSCLC and PS2. Methods: CAPPA-2 was a multicentre, randomized phase III study for first-line treatment of PS2 pts with advanced NSCLC. Patients, aged 18-70, were eligible if they had stage IV or IIIB with malignant pleural effusion or metastatic supraclavicular nodes (TNM VI ed.) and adequate organ function. Patients in standard arm received gemcitabine 1,200 mg/m2 dd1 and 8.Patients in experimental arm received cispaltin 60 mg/m2 d1 plus gemcitabine 1,000 mg/m2 dd1 and 8. All treatments were repeated q3w, up to 4 cycles, unless disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). To have 80% power of detecting hazard ratio (HR) 0.71, corresponding to an increase in median OS from 4.8 to 6.8 months, 285 deaths were required. Results: The study was stopped in June 2012 after the enrolment of 57 pts, due to the slow accrual and the report of positive results from a similar study. Median OS was 3.0 months with single-agent gemcitabine and 5.9 months with cisplatin + gemcitabine (HR 0.52, 95% CI 0.28-0.98, p=0.039). Combination CT produced longer PFS (median 1.7 vs. 3.3 months, HR 0.49, 95% CI 0.27-0.89, p=0.017) and higher response rate (4% vs. 18%, p=0.19), without substantial increase in toxicity. Conclusions: Addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2 patients with advanced NSCLC. Clinical trial information: NCT00526643.

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Association between polymorphisms of DNA repair genes and survival of advanced NSCLC patients treated with platinum-based chemotherapy

Lung Cancer ◽

10.1016/j.lungcan.2011.05.023 ◽

2012 ◽

Vol 75 (1) ◽

pp. 102-109 ◽

Cited By ~ 30

Author(s):

Shengxiang Ren ◽

Songwen Zhou ◽

Fengyin Wu ◽

Ling Zhang ◽

Xuefei Li ◽

...

Keyword(s):

Dna Repair ◽

Advanced Nsclc ◽

Dna Repair Genes ◽

Platinum Based Chemotherapy ◽

Nsclc Patients ◽

Repair Genes

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LKB1 mutations are not associated with the efficacy of first-line and second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC): a post hoc analysis of the TAILOR trial

ESMO Open ◽

10.1136/esmoopen-2020-000748 ◽

2020 ◽

Vol 5 (3) ◽

pp. e000748

Author(s):

Claudio Vernieri ◽

Monica Ganzinelli ◽

Eliana Rulli ◽

Gabriella Farina ◽

Anna Cecilia Bettini ◽

...

Keyword(s):

Advanced Nsclc ◽

Cytotoxic Chemotherapy ◽

Second Line ◽

Small Cell Lung ◽

First Line ◽

Mutational Status ◽

Platinum Based Chemotherapy ◽

Nsclc Patients ◽

The Impact ◽

Chemotherapy Efficacy

PurposeIn patients with advanced lung adenocarcinoma, the impact of LKB1 mutations on cytotoxic chemotherapy efficacy remains poorly explored. Here, we aimed at investigating the potential impact of LKB1 mutational status on chemotherapy efficacy in advanced non-small-cell lung cancer (NSCLC) patients enrolled in the TArceva Italian Lung Optimisation tRial (TAILOR) trial.MethodsThe multicenter TAILOR trial randomised patients with EGFR-wild type (wt) advanced NSCLC progressing on/after previous platinum-based chemotherapy to receive docetaxel or erlotinib. Here, we evaluated the impact of LKB1 mutational status on progression-free survival (PFS) and overall survival (OS) in patients treated with second-line docetaxel/erlotinib or during prior platinum-based chemotherapy.ResultsOut of 222 patients randomised in the TAILOR trial, left-over tumour tissues were available for 188 patients, and 120 patients with evaluable LKB1 status were included. Of them, 17 (14.17%) patients had LKB1-mutated tumours, while 103 (85.83%) had LKB1-wt disease. During second-line treatment, PFS and OS were not statistically significantly different in patients with LKB1-mutated when compared with LKB1-wt NSCLC (adjusted HR (aHR)=1.29, 95% CI 0.75 to 2.21; p=0.364 and aHR=1.41, 95% CI 0.82 to 2.44; p=0.218, respectively). Similarly, we found no significant association between LKB1 mutations and patient PFS or OS during prior first-line platinum-based chemotherapy (aHR=1.04, 95% CI 0.55 to 1.97; p=0.910 and aHR=0.83, 95% CI 0.42 to 1.65; p=0.602, respectively).ConclusionAmong advanced NSCLC patients receiving two lines of systemic therapy, LKB1 mutations were not associated with PFS or OS during second-line docetaxel or prior first-line platinum-based chemotherapy. While larger prospective trials are needed to confirm our findings, cytotoxic chemotherapy remains the backbone of investigational combination strategies in this patient population.

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A randomized phase II multi-institutional trial of anlotinib plus docetaxel versus docetaxel in EGFR-wild-type non-small cell lung cancer (NSCLC) patients after progression on first-line platinum-base chemotherapy: ALTER-L018.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21703 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21703-e21703

Author(s):

Lin Wu ◽

Zhijun Wu ◽

Zemin Xiao ◽

Jie Weng ◽

Zhongsha Ma ◽

...

Keyword(s):

Advanced Nsclc ◽

Phase Iii ◽

Wild Type ◽

First Line ◽

End Points ◽

Phase Iii Trial ◽

Platinum Based Chemotherapy ◽

Group A ◽

Group B ◽

Nsclc Patients

e21703 Background: Anlotinib is an oral VEGFR, FGFR, PDGFR and c-Kit tyrosine kinase inhibitor, which can prolong both PFS and OS of refractory advanced NSCLC patients in phase III trial: ALTER0303. The combination of docetaxel and ramucirumab/nintedanib had been demonstrated activity in the second line therapy setting for NSCLC. We performed ALTER-L018 to assessed the safety and efficacy of anlotinib with docetaxel in EGFR-wild type refractory advanced NSCLC (NCT03624309). Methods: Patients (pts) with EGFR-wild type refractory advanced NSCLC, who failed to first-line platinum-based chemotherapy, were randomized to group A(anlotinib: 12mg QD from day 1 to 14 of a 21-day cycle +docetaxel: 75mg/m2 Q3W) and group B(docetaxel: 75mg/m2 Q3W). The primary end points is PFS, and secondary end points include OS, ORR, DCR and safety. Results: Between January and December 2019, 36 pts were enrolled at 10 institutions in Hunan China, with 31(15 in group A, 16 in group B) of these individuals being evaluable for treatment efficacy and safety. Pt characteristics(group A/ group B): median age: 55(39-70)/57(44-67); male: 73%/81%; non-squamous NSCLC: 86%/75%. Median PFS were 5.3 months (95%CI:2.76-7.85) in group A and 2.3 months (95%CI, 1.14-3.46) in group B (HR 0.42; 95% CI:0.16-1.13; p = 0.047); In group A and B, ORR and DCR were 26.67% versus 0%(p = 0.043), 60.00% versus 31.25%(p = 0.16), respectively. Among 31 pts, 89% of treatment-related AEs (TRAEs) were grade 1 or 2, and the most common TRAEs in group A were hand-foot syndrome, pruritus and insomnia of 13%(2/15) each; in group B were alopecia, constipation and anemia of 12%(1/16) each. Toxicities≥grade 3(TRAEs) included: neutropenia, leukopenia, diarrhea and hrombocytopenia, 6.6%(1/15) each in group A. There was 1 grade 5 AE in group A. Conclusions: This combination of anlotinib and docetaxel with significant difference PFS prolonging and manageable safety profile, is a viable option in relapsed NSCLC, should be considered following progression on platinum-based chemotherapy. It will be further explored in a randomized phase III trial. Clinical trial information: NCT03624309.

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Association of XRCC3 and XPD751 SNP with efficacy of platinum-based chemotherapy in advanced NSCLC patients

Clinical & Translational Oncology ◽

10.1007/s12094-012-0785-3 ◽

2012 ◽

Vol 14 (3) ◽

pp. 207-213 ◽

Cited By ~ 17

Author(s):

Xiaoxia Chen ◽

Hui Sun ◽

Shengxiang Ren ◽

Vikramsingh Kim Curran ◽

Ling Zhang ◽

...

Keyword(s):

Advanced Nsclc ◽

Platinum Based Chemotherapy ◽

Nsclc Patients

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Predictive Effects of ERCC1 and XRCC3 SNP on Efficacy of Platinum-based Chemotherapy in Advanced NSCLC Patients

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyq071 ◽

2010 ◽

Vol 40 (10) ◽

pp. 954-960 ◽

Cited By ~ 35

Author(s):

C. Zhou ◽

S. Ren ◽

S. Zhou ◽

L. Zhang ◽

C. Su ◽

...

Keyword(s):

Advanced Nsclc ◽

Platinum Based Chemotherapy ◽

Nsclc Patients

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Pembrolizumab Alone or Combined With Chemotherapy in Advanced NSCLC With PD-L1 ≥50%: Results of a Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.691519 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ya Chen ◽

Yanan Wang ◽

Zhengyu Yang ◽

Minjuan Hu ◽

Yanwei Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Survival Rates ◽

Progression Free Survival ◽

Standard Of Care ◽

Programmed Death ◽

Platinum Based Chemotherapy ◽

Prospective Trials ◽

Nsclc Patients

ObjectivesPembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy (PM) both become standard of care in patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50%. This study aimed to figure out the better treatment choice.MethodIn this retrospective analysis, we compared the clinical efficacy of PM and PC as first-line treatment in NSCLC patients with a PD-L1 ≥50% and negative for genomic alterations in the EGFR and ALK genes.ResultAmong the population, 115 patients received PC, and 91 patients received PM. Up to Dec 30, 2020, median follow-up was 17.13 months. The median progression-free survival (PFS) rates of PC and PM were 12.37 and 9.60 months (HR: 0.44, p < 0.001), respectively. The median overall survival (OS) rates were NE and 28.91 months (HR: 0.40, p = 0.005), respectively. Subgroup analysis found that the PFS benefit of PC was evident in most subgroups excepting patients with brain metastasis. The 1-year overall survival rates of PC and PM were 89.3% and 76.1%, respectively. The ORR was 61.7 and 46.9% (p = 0.004), respectively.ConclusionIn patients with previously untreated, PD-L1 ≥50%, advanced NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard platinum-based chemotherapy seems to be the preferred treatment, which needs to be validated by further prospective trials.

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