scholarly journals Efficacy of Single-site Radiotherapy Plus PD-1 Inhibitors vs PD-1 Inhibitors for Oligometastatic Non-Small Cell Lung Cancer

Author(s):  
Peiliang Wang ◽  
Tianwen Yin ◽  
Kaikai Zhao ◽  
Jinming Yu ◽  
Feifei Teng

Abstract Purpose: Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aim to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. Methods: We retrospectively identified oligometastatic NSCLC (≤4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS) . Results: Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of radiotherapy to ICI therapy significant increased the best ORR from 31.2% to 50.8%, p=0.015). The out-of-field (abscopal`) response rate could reach 41.3% (95% CI, 26.5%-56.1%) in the ICI plus RT group. Median progression-free survival was 8.9 months (95%CI, 4.7-13.1 months) with ICI alone versus 13.8 months (95% CI, 9.5-18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.568; p=0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients with aged <65 years (p=0.016), patients with ECOG PS=0 (p=0.048), patients with 1-2 metastatic sites (p=0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm.Conclusion: Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.

2007 ◽  
Vol 25 (36) ◽  
pp. 5777-5784 ◽  
Author(s):  
Charles A. Butts ◽  
David Bodkin ◽  
Edward L. Middleman ◽  
Craig W. Englund ◽  
David Ellison ◽  
...  

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.


Author(s):  
Peiliang Wang ◽  
Tianwen Yin ◽  
Kaikai Zhao ◽  
Jinming Yu ◽  
Feifei Teng

Abstract Purpose Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aimed to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. Methods We retrospectively identified oligometastatic NSCLC (< 4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS). Results Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of RT to ICI therapy significantly increased the best ORR from 31.2% to 50.8% (p = 0.015). The out-of-field (abscopal effect) response rate could reach 41.3% (95%CI 26.5%–56.1%) in the ICI plus RT group. Median PFS was 8.9 months (95%CI 4.7–13.1 months) with ICI alone versus 13.8 months (95%CI 9.5–18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.556; p = 0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients aged < 65 years (p = 0.016), patients with ECOG PS = 0 (p = 0.048), and patients with 1–2 metastatic sites (p = 0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm. Conclusion Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.


2020 ◽  
Author(s):  
Mariano Provencio ◽  
Josefa Terrasa ◽  
Pilar Garrido ◽  
Rosario García Campelo ◽  
Francisco Aparisi ◽  
...  

Abstract Background: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain.Methods: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. 155 patients were enrolled (August 2016-December 2018) from 30 sites. Primary objective: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources.Results: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. 155 patients were evaluable for response, 1.3% complete response, 40.7% partial response, 31% stable disease and 11.6% progressive disease. Objective response rate was 42%. Median progression-free survival was 9.4 months. 49% reported an adverse event, the majority of which (78%) were grade 1 or 2. The resource cost study indicates early use is warranted. Conclusion: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events.Clinical trial registration number: NCT03790397


2017 ◽  
Vol 35 (4) ◽  
pp. 412-420 ◽  
Author(s):  
David R. Spigel ◽  
Martin J. Edelman ◽  
Kenneth O’Byrne ◽  
Luis Paz-Ares ◽  
Simonetta Mocci ◽  
...  

Purpose The phase III OAM4971g study (METLung) examined the efficacy and safety of onartuzumab plus erlotinib in patients with locally advanced or metastatic non–small-cell lung cancer selected by MET immunohistochemistry whose disease had progressed after treatment with a platinum-based chemotherapy regimen. Patients and Methods Patients were randomly assigned at a one-to-one ratio to receive onartuzumab (15 mg/kg intravenously on day 1 of each 21-day cycle) plus daily oral erlotinib 150 mg or intravenous placebo plus daily oral erlotinib 150 mg. The primary end point was overall survival (OS) in the intent-to-treat population. Secondary end points included median progression-free survival, overall response rate, biomarker analysis, and safety. Results A total of 499 patients were enrolled (onartuzumab, n = 250; placebo, n = 249). Median OS was 6.8 versus 9.1 months for onartuzumab versus placebo (stratified hazard ratio [HR], 1.27; 95% CI, 0.98 to 1.65; P = .067), with a greater number of deaths in the onartuzumab arm (130 [52%] v 114 [46%]). Median progression-free survival was 2.7 versus 2.6 months (stratified HR, 0.99; 95% CI, 0.81 to 1.20; P = .92), and overall response rate was 8.4% and 9.6% for onartuzumab versus placebo, respectively. Exploratory analyses using MET fluorescence in situ hybridization status and gene expression showed no benefit for onartuzumab; patients with EGFR mutations showed a trend toward shorter OS with onartuzumab treatment (HR, 4.68; 95% CI, 0.97 to 22.63). Grade 3 to 5 adverse events were reported by 56.0% and 51.2% of patients, with serious AEs in 33.9% and 30.7%, for experimental versus control arms, respectively. Conclusion Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter OS in the onartuzumab arm, compared with erlotinib in patients with MET-positive non–small-cell lung cancer.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mariano Provencio ◽  
Josefa Terrasa ◽  
Pilar Garrido ◽  
Rosario García Campelo ◽  
Francisco Aparisi ◽  
...  

Abstract Background AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. Methods Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016–December 2018) from 30 sites. Primary objective: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. Results 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. Conclusion This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. Trial registration Clinical trial registration number:NCT03790397.


2010 ◽  
Vol 28 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Suresh S. Ramalingam ◽  
Michael L. Maitland ◽  
Paul Frankel ◽  
Athanassios E. Argiris ◽  
Marianna Koczywas ◽  
...  

Purpose Vorinostat, a histone deacetylase inhibitor, exerts anticancer effects by both histone and nonhistone–mediated mechanisms. It also enhances the anticancer effects of platinum compounds and taxanes in non–small-cell lung cancer (NSCLC) cell lines. This phase II randomized, double-blinded, placebo-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxel in patients with advanced-stage NSCLC. Patients and Methods Patients with previously untreated stage IIIB (ie, wet) or IV NSCLC were randomly assigned (2:1) to carboplatin (area under the curve, 6 mg/mL × min) and paclitaxel (200 mg/m2 day 3) with either vorinostat (400 mg by mouth daily) or placebo. Vorinostat or placebo was given on days 1 through 14 of each 3-week cycle to a maximum of six cycles. The primary end point was comparison of the response rate. Results Ninety-four patients initiated protocol therapy. Baseline patient characteristics were similar between the two arms. The median number of cycles was four for both treatment arms. The confirmed response rate was 34% with vorinostat versus 12.5% with placebo (P = .02). There was a trend toward improvement in median progression-free survival (6.0 months v 4.1 months; P = .48) and overall survival (13.0 months v 9.7 months; P = .17) in the vorinostat arm. Grade 4 platelet toxicity was more common with vorinostat (18% v 3%; P < .05). Nausea, emesis, fatigue, dehydration, and hyponatremia also were more frequent with vorinostat. Conclusion Vorinostat enhances the efficacy of carboplatin and paclitaxel in patients with advanced NSCLC. HDAC inhibition is a promising therapeutic strategy for treatment of NSCLC.


2014 ◽  
Vol 76 (5) ◽  
pp. 218 ◽  
Author(s):  
Myoung-Rin Park ◽  
Yeon-Hee Park ◽  
Jae-Woo Choi ◽  
Dong-Il Park ◽  
Chae-Uk Chung ◽  
...  

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