Radiotherapy to augment pembrolizumab responses and outcomes in metastatic non-small cell lung cancer: Pooled analysis of two randomized trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9548-9548
Author(s):  
James William Welsh ◽  
Dawei Chen ◽  
Paul Baas ◽  
Joe Y. Chang ◽  
Vivek Verma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Randomized Trials ◽  
Small Sample Size ◽  
Response Rates ◽  
Pooled Analysis ◽  
Small Cell ◽  
Small Sample ◽  
Small Cell Lung

9548 Background: In metastatic non-small cell lung cancer (mNSCLC), the clinical trials NCT02492568 and NCT02444741 are the only known randomized comparisons of pembrolizumab alone versus pembrolizumab combined with radiation therapy (RT). When the trials were analyzed individually, some potential benefit was observed in the combination therapy group, but the relatively small sample size of each trial limited the detection of potential differences in response rates and outcomes. Hence, we perform a pooled analysis of these two randomized trials to validate and explore whether RT improves mNSCLC patient responses to immunotherapy. Methods: This was a pooled analysis of two randomized trials (NCT02492568 and NCT02444741) of pembrolizumab with or without RT for mNSCLC. Endpoints included the out-of-field overall response rate (ORR) and disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and subgroup analysis of the different RT schemes. Results: In all, 131 patients were analyzed (n = 66 pembrolizumab; n = 65 pembrolizumab/RT (iRT)). ORR was 21% in the pembrolizumab arm vs. 38% in the iRT arm (p = 0.01); DCR was 53% in the pembrolizumab arm vs. 67% in the iRT arm (p = 0.0009); PFS was 4.4 m vs 8.3 m (p = 0.046); and OS was 9.2 m vs 19.2 m (HR 0.66; p = 0.040). Ablative RT (24Gy/3 fractions and 50Gy/4 fractions) had better ORRs of 48% and 54%, respectively, compared to 18% for non-ablative RT (45Gy/15 fractions) and 20% for pembrolizumab alone (p < 0.05, respectively). Conclusions: The addition of RT to immunotherapy significantly increased the ORR of unirradiated lesions and was additionally associated with significant improvements in PFS and OS. Ablative RT was associated with response rates significantly higher than those of non-ablative RT, possibly due to a detrimental effect of non-ablative RT on ALC. These hypothesis-generating findings require dedicated, large-volume, and randomized studies for corroboration. Clinical trial information: NCT02492568 and NCT02444741 .

scholarly journals The influence of sex and histology on outcomes in non-small-cell lung cancer: a pooled analysis of five randomized trials

2010 ◽  
Vol 21 (10) ◽  
pp. 2023-2028 ◽  
Author(s):  
P. Wheatley-Price ◽  
F. Blackhall ◽  
S.-M. Lee ◽  
C. Ma ◽  
L. Ashcroft ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Randomized Trials ◽  
Pooled Analysis ◽  
Small Cell ◽  
Small Cell Lung

Xanthine oxidoreductase and chemosensitivity in non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11077-11077
Author(s):  
R. Myint ◽  
M. Batus ◽  
P. Bonomi ◽  
P. Gattuso ◽  
W. H. Warren ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Small Sample Size ◽  
Small Cell ◽  
Small Sample ◽  
Xanthine Oxidoreductase ◽  
Small Cell Lung ◽  
Clin Pathol

11077 Background: Xanthine oxidoreductase (XOR) is an enzyme involved in the degradation of purines into uric acid and reactive oxygen species and activation of the MAP kinase pathway involved in apoptosis. Decreased XOR expression was shown in recent studies to be associated with more aggressive disease in breast (Linder et al. Clin Cancer Res. 2005;11:4372–4381) and gastric cancers (Linder et al. J Clin Pathol. 2006;59:965–971). The goal of our study was to show that decreased XOR expression was associated with decreased survival in non-small cell lung cancer (NSCLC). Methods: Tissue specimens from 82 patients (pts) were stained using a XOR specific antibody (36 male and 46 female, age range from 40 to 92 years). These included 41 adenocarcinoma, 31 squamous cell, 8 poorly/moderately differentiated, and 2 bronchioloalveolar. XOR staining intensity was measured on a scale of 0 through 4 (0 being no staining). XOR intensity was correlated with clinical characteristics and outcomes using log rank and COX PH regression analysis. Results: Of the 82 pts, 34 received adjuvant chemo, and of these, 15 specimens had low XOR intensity (0–1). These 15 pts received adjuvant chemo and had a median survival of 543 days. In comparison, 19 of the 34 pts receiving adjuvant chemo had specimens with high XOR intensity (2–4). Their median survival was significantly longer at 2,023 days (p=0.007, hazard ratio=0.33). Conclusions: Although we had a small sample size, in our retrospective study, we found that pts who received adjuvant chemo had a longer survival if their tumors expressed high levels of XOR. XOR could be a potential predictor for responsiveness to adjuvant chemo in patients with NSCLC. Pts with decreased XOR may be less responsive to chemo and thus be able to avoid a toxic treatment if it is not significantly beneficial. [Table: see text] No significant financial relationships to disclose.

scholarly journals Safety Related to the Timing of Radiotherapy and Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer: A Single Institutional Experience

2022 ◽  
Vol 29 (1) ◽  
pp. 221-230
Author(s):  
Michael C. Tjong ◽  
Malavan Ragulojan ◽  
Ian Poon ◽  
Alexander V. Louie ◽  
Susanna Y. Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Sample Size ◽  
Small Cell ◽  
Small Sample ◽  
Small Cell Lung

Background: The safety impact of radiotherapy (RT) timing relative to immune checkpoint inhibitors (ICIs) for advanced non-small-cell lung cancer (NSCLC) is unclear. We investigated if RT within 14 days (Interval 1) and 90 days (Interval 2) of ICI use is associated with toxicities compared to RT outside these intervals. Methods: Advanced NSCLC patients treated with both RT and ICIs were reviewed. Toxicities were graded as per CTCAE v4.0 and attributed to either ICIs or RT by clinicians. Associations between RT timing and Grade ≥2 toxicities were analyzed using logistic regression models adjusted for patient, disease, and treatment factors (α = 0.05). Results: Sixty-four patients were identified. Twenty received RT within Interval 1 and 40 within Interval 2. There were 20 Grade ≥2 toxicities in 18 (28%) patients; pneumonitis (6) and nausea (2) were most prevalent. One treatment-related death (immune encephalitis) was observed. Rates of patients with Grade ≥2 toxicities were 35%/25% in the group with/without RT within Interval 1 and 30%/25% in the group with/without RT within Interval 2. No significant association between RT timing relative to ICI use period and Grade ≥2 toxicities was observed. Conclusion: Albeit limited by the small sample size, the result suggested that pausing ICIs around RT use may not be necessary.

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