scholarly journals Are anti-PD1 and anti-PD-L1 alike? The non-small-cell lung cancer paradigm

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
Giuseppe Luigi Banna ◽  
Ornella Cantale ◽  
Melissa Bersanelli ◽  
Marzia Del Re ◽  
Alex Friedlaender ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Indirect Evidence ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Nsclc Patients

Anti-PD1 and anti-PD-L1 agents may have intrinsic and clinically relevant differences in the treatment of non-small cell lung cancer (NSCLC) patients. By reviewing currently available indirect evidence on these agents for NSCLC treatment, highlighting possible inter- and intra-class dissimilarities, anti-PD1 agents showed a higher response rate and a better outcome when combined with chemotherapy for the first-line treatment of patients with squamous and PD-L1 low advanced NSCLC, as compared to anti-PD-L1 agents. Conversely, anti-PD-L1 agents were responsible for less severe adverse events (AEs), particularly, immunerelated AEs. These differences could be explained by their different specific properties. Considering possible differences between anti-PD1 and anti-PD-L1 agents could be clinically relevant for treatment tailoring and inspiring new investigational approaches.

scholarly journals PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

2021 ◽  
Vol 10 (7) ◽  
pp. 1365
Author(s):  
Margarita Majem ◽  
Manuel Cobo ◽  
Dolores Isla ◽  
Diego Marquez-Medina ◽  
Delvys Rodriguez-Abreu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Potential Biomarker ◽  
Nsclc Patients

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.

Biweekly docetaxel and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18147-18147
Author(s):  
E. Gaspar ◽  
J. Firvida ◽  
M. Amenedo ◽  
D. Orts ◽  
M. Salgado ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line

18147 Background: The activity and tolerability of third-generation agents led many investigators to evaluate doublet combinations in the hope that platinum analogues could be eliminated from the treatment of advanced NSCLC. To improve the therapeutic index of this combination, we performed a study with biweekly gemcitabine and docetaxel. Primary objective was determination of objective response rate (ORR). Secondary objectives were time to progression, tolerability and overall survival. Methods: Patients histologically confirmed of non-small cell lung cancer, aged ≥ 18, ECOG PS 0–2, measurable lesion according RECIST criteria, adequate bone marrow, renal and hepatic function were included. Prior chemotherapy was not allowed. Patients received treatment with a combination of Docetaxel 50 mg/m2 and gemcitabine 20,00 mg/m2 each 15 days for a maximum of 8 cycles. Results: Fifty patients were included between July 2005 and October 2006.Now we present the results of the first 32 patients: 88% were male, median age was 62.7 years old, 69% had ECOG 0–1 and 81% of patients had stage IV. Histology was squamous cell carcinoma (53%) adenocarcinoma (31%) and large cell carcinoma (16%). A total 221 cycles were administrated . Over 30 patients evaluable for response, none achieved CR, 11 PR (36%), 7 SD (23%) and 12 PD, with an overall response rate of 36%. Median follow up of patients is 16 months, with a median overall survival of 9 months. Grade 3–4 toxicity per patient was: neutropenia (6%).Grade 1–2 toxicity per patient asthenia (75%), and nauseas (30%). Conclusions: These results suggest that biweekly schedule of gemcitabine / docetaxel is a safe and active regimen in first line advanced NSCLC patients.Updated results will be presented. No significant financial relationships to disclose.

scholarly journals Efficacy of Combination Chemo-Immunotherapy as a First-Line Treatment for Advanced Non-Small-Cell Lung Cancer Patients With HER2 Alterations: A Case Series

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuang Zhao ◽  
Xinghong Xian ◽  
Panwen Tian ◽  
Weimin Li ◽  
Ke Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Nsclc Patients ◽  
First Line Treatment

ObjectiveAlthough the treatment of non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) alterations has been studied for years, the overall response rate (ORR) of these patients is still unsatisfactory, and more therapeutic strategies are needed. Little is known about the combination of chemo- and immunotherapy in HER2-altered lung cancer treatment.Materials and MethodsWe report five cases of advanced NSCLC with HER2 insertion mutation or amplification treated with immunotherapy combined with chemotherapy as the first-line treatment. The HER2 alteration type, duration of treatment and survival were also analyzed.ResultsThe five advanced NSCLC patients, three with HER2 mutations and two with HER2 amplifications, received chemo-immunotherapy as the first-line treatment. The average patient age was 54.6 years. Three patients were females, and two were males. Among all the patients, only one had a smoking history. The immunotherapies used were as follows: two patients were treated with sintilimab, and three patients were treated with pembrolizumab. Only one patient had squamous carcinoma, and she was also the only patient with a complete response (CR). The progression-free survival (PFS) ranged from 2-12 months, with a median PFS of 8.0 months.ConclusionsChemo-immunotherapy may be a promising first-line treatment option for NSCLC patients with HER2 alterations. Further clinical trials are required to confirm this therapeutic option.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

scholarly journals Circulating mRNA Expression of astrocyte-Elevated Gene-1 Associated with Treatment Response and Survival in Non-Small Cell Lung Cancer Patients Treated with Pemetrexed

2021 ◽  
Author(s):  
You-Lung Chang ◽  
Yen-Fu Chen ◽  
Ying-Yin Chen ◽  
Shih-Chieh Chang ◽  
Cheng-Yu Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Treatment Response ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Nsclc Patients

Abstract Backgrounds: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumor response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed advanced NSCLC were enrolled to be treated with pemetrexed combined platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR.Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of SD (n = 13) and PD (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS) and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR v.s. SD or PD, AEG-1: 1.22 ± 0.80 v.s. 4.51 ± 15.45, p = 0.043). NSCLC patients had elevated AEG-1 (AEG-1 ≥ 2) after 2-cycle chemotherapy had shorter PFS and OS (high AEG-1 v.s. low AEG-1, median, PFS: 5.5 v.s. 11.9 months, p = 0.021; OS: 25.9 v.s. 40.8 months, p = 0.019, respectively). In Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival.Conclusion: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.

scholarly journals Does Pemetrexed Work in Targetable, Nonsquamous Non-Small-Cell Lung Cancer? A Narrative Review

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2658
Author(s):  
Jin-Yuan Shih ◽  
Akira Inoue ◽  
Rebecca Cheng ◽  
Rocio Varea ◽  
Sang-We Kim
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Narrative Review ◽  
Small Cell Lung ◽  
First Line ◽  
Anaplastic Lymphoma

Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed–platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First- and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK- and ROS1-positive patients and longer than that in patients with Kirsten rat sarcoma (KRAS) virus proto-oncogene mutations or WTD, although the available studies were limited. For Erb-b2 receptor tyrosine kinase 2 (ERRB2) mutations, first-line pemetrexed showed outcomes similar to those for EGFR and KRAS alterations. Data on pemetrexed in patients with KRAS mutations or MNNG HOS-transforming (MET) expression were limited. Pemetrexed could be an option for first- and second-line treatment for TKI failure in nonsquamous advanced NSCLC with select targetable driver mutations.

Randomized Phase III Study of Gemcitabine-Cisplatin Versus Etoposide-Cisplatin in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 12-12 ◽  
Author(s):  
Felipe Cardenal ◽  
M. Paz López-Cabrerizo ◽  
Antonio Antón ◽  
Vicente Alberola ◽  
Bartomeu Massuti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

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