scholarly journals Efficacy of immune checkpoint inhibitor therapy in patients with RET fusion-positive non-small-cell lung cancer

Immunotherapy ◽  
2021 ◽  
Author(s):  
Naleen Raj Bhandari ◽  
Lisa M Hess ◽  
Yimei Han ◽  
Yajun E Zhu ◽  
Anthony N Sireci
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival

Aim: To describe outcomes of patients with RET fusion-positive non-small-cell lung cancer (NSCLC) who received immune checkpoint inhibitor (ICI)-based treatments in the US. Patients & methods: Using de-identified Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic and Guardant Health databases, treatment patterns and outcomes of 69 patients with advanced/metastatic RET fusion-positive NSCLC who received ICI-based treatment were described. Results: Median real-world progression-free survival and overall survival months were 4.2 (95% CI: 1.4–8.4) and 19.1 (6.9–not reached), respectively, among patients in Clinico-Genomic database (n = 17) receiving first-line ICI-based therapy. In the Guardant Health database, progression-free survival was unavailable, and the median overall survival was not reached (n = 29). Conclusion: Outcomes associated with ICI-based treatments in the first-line setting among patients with RET fusion-positive NSCLC are consistent with unselected populations reported in literature.

A multicenter, open label, randomized phase III study of atezolizumab with platinum-pemetrexed and with or without bevacizumab for patients with advanced nonsquamous non-small cell lung cancer (WJOG11218L APPLE Study).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9125-TPS9125 ◽  
Author(s):  
Yoshimasa Shiraishi ◽  
Haruko Daga ◽  
Satoshi Ikeda ◽  
Akito Hata ◽  
Hideaki Mizutani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Combination Therapy ◽  
Disease Progression ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

TPS9125 Background: First-line treatment of non–small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with an immune-checkpoint inhibitor. Bevacizumab is expected to enhance not only chemotherapy but also the efficacy of immune-checkpoint inhibitors through blockade of vascular endothelial growth factor–mediated immunosuppression. The aim of this trial is to demonstrate an additional effect of bevacizumab administered together with platinum combination therapy and the immune-checkpoint inhibitor atezolizumab in patients with advanced nonsquamous NSCLC. Methods: Cytotoxic chemotherapy–naïve patients aged 20 years or older with a performance status of 0 or 1 are randomly assigned in a 1:1 ratio to receive either atezolizumab plus pemetrexed-carboplatin (APP) or atezolizumab, pemetrexed-carboplatin, and bevacizumab (APPB). Patients with genetic driver alterations such as those affecting EGFR or ALK are included if they have experienced disease progression or unacceptable side effects during treatment with at least one approved tyrosine kinase inhibitor. After four cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab plus pemetrexed plus bevacizumab is administered for up to 2 years until evidence of disease progression or development of unacceptable toxicity. The primary end point is progression-free survival (according to central image review). Secondary end points are progression-free survival (determined by the attending physician), overall survival, response rate, response duration, and adverse events. Stratification factors are PD-L1 tumor proportion score (≥50% vs. < 50%), stage, and driver gene alterations. We determined that, with a sample size of 350 patients (175 in each arm), the trial will have 80% power to show a hazard ratio for disease progression or death of 0.727 at a one-sided alpha level of 0.025 (as calculated on the basis of 311 such events) for comparison between the APPB and APP groups. Clinical trial information: 194565.

Randomized Phase II Study of Gemcitabine Plus Cisplatin or Carboplatin, With or Without Cetuximab, As First-Line Therapy for Patients With Advanced or Metastatic Non–Small-Cell Lung Cancer

2007 ◽  
Vol 25 (36) ◽  
pp. 5777-5784 ◽  
Author(s):  
Charles A. Butts ◽  
David Bodkin ◽  
Edward L. Middleman ◽  
Craig W. Englund ◽  
David Ellison ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival

PurposeTo evaluate the efficacy of cetuximab added to first-line gemcitabine/platinum in chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC).Patients and MethodsIn this noncomparative, randomized trial, chemotherapy-naïve patients with recurrent/metastatic NSCLC (stage IV or stage IIIB with malignant pleural effusion) were eligible. Patients received cisplatin (75 mg/m2IV, every 3 weeks) or carboplatin (area under the concentration-versus-time curve of 5 intravenously [IV], every 3 weeks), and gemcitabine (1,250 or 1,000 mg/m2IV, days 1 and 8) plus cetuximab (400 mg/m2IV day 1, followed by 250 mg/m2weekly), in arm A, or chemotherapy alone, in arm B. Response rate was the primary end point; safety, progression-free survival, and overall survival were secondary end points.ResultsSixty-five patients were randomly assigned to arm A and 66 to arm B. Partial responses were observed in 18 patients (27.7%; 95% CI, 17.3 to 40.2) in arm A and 12 (18.2%; 95% CI, 9.8 to 29.6) in arm B. Median progression-free survival was 5.09 months for arm A (95% CI, 4.17 to 5.98) and 4.21 months (95% CI, 3.81 to 5.49) in arm B. Median overall survival was 11.99 months (95% CI, 8.80 to 15.18) and 9.26 months (95% CI, 7.43 to 11.79) in arms A and B, respectively. Overall toxicity was acceptable and consistent with the profiles of the individual agents.ConclusionFirst-line treatment with cetuximab plus gemcitabine/platinum is well tolerated and can be administered safely in patients with advanced NSCLC. Differences in response rate, progression-free survival, and overall survival suggest that the addition of cetuximab to platinum/gemcitabine may improve clinical outcomes. Larger studies are in progress to address this hypothesis.

scholarly journals Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Nathaniel Wiest ◽  
Umair Majeed ◽  
Karan Seegobin ◽  
Yujie Zhao ◽  
Yanyan Lou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Novel Approaches ◽  
Line Setting ◽  
Egfr Tki

Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with epidermal growth factor receptor (EGFR) gene mutant (EGFRm) NSCLC, newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitor combinations are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and active avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.

scholarly journals Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study

2021 ◽  
pp. JCO.20.03579 ◽  
Author(s):  
Michael Boyer ◽  
Mehmet A. N. Şendur ◽  
Delvys Rodríguez-Abreu ◽  
Keunchil Park ◽  
Dae Ho Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Metastatic Nsclc

PURPOSE Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. METHODS In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234 ), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. RESULTS Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. CONCLUSION Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.

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