Radiotherapy and Tyrosine Kinase Inhibitors in Stage IV Non-small Cell Lung Cancer: Real-life Experience

Borghetti, Paolo; Bonù, Marco Lorenzo; Roca, Elisa; Pedretti, Sara; Salah, Emiliano; Baiguini, A.; Greco, Diana; Triggiani, Luca; Maddalo, Marta; Levra, Niccolò Giaj; Alongi, Filippo; Magrini, Stefano Maria; Buglione, Michela

doi:10.21873/invivo.11219

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…The median duration regarding the administration of EGFR-TKI prior to radiotherapy was 5.4 months (range: 0.3-47.3 months). 43 In our study, we found that there was a tendency for patients to receive more benefits if local radiotherapy began within 24 weeks after the start of EGFR-TKI, as compared to those who began after more than 24 weeks. This could be the synergistic effect, as EGFR-TKI displays its maximum activity after 4 months of drug use.…”

Section: Discussionmentioning

confidence: 56%

Primary Tumor Radiotherapy During EGFR-TKI Disease Control Improves Survival of Treatment Naïve Advanced EGFR-Mutant Lung Adenocarcinoma Patients

Hsu

Huang

Tseng

et al. 2021

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Background Whether radiotherapy only for primary lung tumor (RTPLT) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves survival of treatment naïve advanced EGFR -mutant lung adenocarcinoma (LAD) patients with/without polymetastasis. Materials and Methods This was a retrospective, single-center, observational study. Patients with stage IIIB-IV EGFR -mutant LAD with disease control by EGFR-TKI therapy were divided into curative RTPLT, and control, without radiotherapy (WRTPLT) groups. Results A total of 138 patients were enrolled; 46 in the RTPLT group and 92 in the WRTPLT group. Amongst them, 37% had oligometastasis, and 26.1% brain metastasis. The RTPLT group had both significantly longer progression-free survival (PFS) (27.5 months [95% CI 18.1–36.9] vs 10.9 months [95% CI 6.3–15.5], P<0.001) and overall survivor (OS) (NR [95% CI NR-NR] vs 38.0 months [95% CI 31.2–44.8], P<0.001), respectively, when compared to the WRTPLT group. In multivariate analysis, the adjusted HR of radiotherapy on PFS was 0.30 (0.19–0.47) and on OS, 0.11 (0.04–0.30). Patients with oligometastasis had significantly longer PFS than those with polymetastasis with an HR of 0.35 (0.14–0.85), P=0.02. Patients with either oligometastasis or polymetastasis had significant longer PFS when undergoing radiotherapy than those without (both P<0.05). An EGFR-TKI to radiotherapy interval <24 weeks seemed more beneficial (P=0.097). Radiation pneumonitis comprised 32 (69.6%), 12 (26.1%), and two (4.3%) cases of common terminology criteria grade I, II, and III, respectively. Conclusion Curative RTPLT can prolong survival in patients with LAD following EGFR-TKI disease control, both involving oligometastasis and polymetastasis. RTPLT within 24 weeks after EGFR-TKI initiation appeared to be more beneficial with tolerable radiation pneumonitis.

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Section: Discussionmentioning

confidence: 56%

Primary Tumor Radiotherapy During EGFR-TKI Disease Control Improves Survival of Treatment Naïve Advanced EGFR-Mutant Lung Adenocarcinoma Patients

Hsu

Huang

Tseng

et al. 2021

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“…Our findings support the idea that concomitant IR + ALKi therapy does not lead to a significant increase of cell death at concentrations equal to serum concentrations, which might not lead to a relevant immunogenic trigger for the immune system. Cells responded stronger to first-generation KI crizotinib, due to a smaller specificity and possible off-target effects based on the additional effect on different kinases like c-Met and RON [33] . Interestingly, alectinib led to stronger decrease of number of colonies in our colony forming assay.…”

Section: Discussionmentioning

confidence: 99%

Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells

et al. 2022

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“…A more recent clinical trial has demonstrated the role of conventional radiotherapy and SBRT in patients with EGFR-mutant or anaplastic lymphoma kinase rearrangement-positive metastatic NSCLC. [65] . Among these patients, there were 50 with an mOS of 19.3 months and 1- and 2-year OS of 71.5% and 36.5%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials

et al. 2019

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Background: Preclinical in vitro experiments demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) might have synergistic effect in combination with radiotherapy on Non-small cell lung cancer (NSCLC), but the clinical trials showed inconsistence results in NSCLC patients with EGFR status unknow or mutations. This study aimed to determine if added TKIs to Thoracic radiotherapy (TRT) improve primary disease response rate (RR) and survival outcomes in advanced or metastatic NSCLC. Methods: We searched MEDLINE, EMBASE, and Cochrane Library from January 2000 to December 2017 for eligible studies where patients received concurrent EGFR TKIs and TRT or CRT. Concerned outcomes were primary tumor RR, overall survival (OS), and adverse events (AEs). The meta-analysis was performed using Stata software (version 12.0). Random effects models were used to pool outcomes across studies. Sensitivity analysis was performed to determine if the results would be different. Results: We found 16 prospective clinical trials with mature results for meta-analyses. Twelve studies including 446 patients reported the RR and survival outcomes of TRT combined TKIs. The CR, PR, SD, and PD, respectively, were 0.06 (95% CI 0.03–0.09, I 2 = 0%), 0.44 (95% CI 0.38–0.49, I 2 = 64.9%), 0.29 (95% CI 0.24–0.34, I 2 = 78.4%), and 0.15 (95% CI 0.11–0.19, I 2 = 84.2%). One- and 2-year OS, respectively, were 0.52 (95% CI 0.44–0.60, I 2 = 38.8%) and 0.26 (95% CI 0.18–0.33, I 2 = 0%). Four studies including 182 patients reported the RR and survival outcomes of CRT combined TKIs. The pooled CR, PR, SD, and PD, respectively, were 0.12 (95% CI 0.02–0.22, I 2 = 69.1%), 0.41 (95% CI 0.27–0.55, I 2 = 71.6%), 0.31 (95% CI 0.16–0.46, I 2 = 79%), and 0.14 (95% CI −0.01–0.30, I 2 = 87.8%). Only 1 study reported the survival event rate, 1- and 2-year OS, respectively, were 0.83 (95% CI 0.71–0.94) and 0.67 (95% CI 0.54–0.81). There were not severe adverse events (SAEs) reported either TRT combined TKIs or CRT combined TKIs. Conclusion: There is evidence, albeit of low quality, that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone, TRT alone or CRT.

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Radiotherapy and Tyrosine Kinase Inhibitors in Stage IV Non-small Cell Lung Cancer: Real-life Experience

Cited by 12 publications

References 23 publications

Primary Tumor Radiotherapy During EGFR-TKI Disease Control Improves Survival of Treatment Naïve Advanced EGFR-Mutant Lung Adenocarcinoma Patients

Primary Tumor Radiotherapy During EGFR-TKI Disease Control Improves Survival of Treatment Naïve Advanced EGFR-Mutant Lung Adenocarcinoma Patients

Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells

Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials

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