Immune Checkpoint Inhibitor Nivolumab and Radiotherapy in Pretreated Lung Cancer Patients

Fiorica, Francesco; Belluomini, Lorenzo; Stefanelli, Antonio; Santini, Alessandra; Urbini, Benedetta; Giorgi, Carlotta; Frassoldati, Antonio

doi:10.1097/coc.0000000000000428

Cited by 57 publications

(59 citation statements)

References 21 publications

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“…Shaverdian et al reported that any previous treatment with RT in patients with advanced NSCLC receiving pembrolizumab was associated with longer PFS and OS . They analyzed the clinical features of a subset of 97 patients administered pembrolizumab in the phase I KEYNOTE001 trial.…”

Section: Discussionmentioning

confidence: 99%

“…Shaverdian et al reported that any previous treatment with RT in patients with advanced NSCLC receiving pembrolizumab was associated with longer PFS and OS. 9 They analyzed the clinical features of a subset of 97 patients administered pembrolizumab in the phase I KEYNOTE001 trial. Forty-two (43%) of the 97 patients were administered any previous RT before the initiation of pembrolizumab, 38 (39%) were administered extracranial RT, and 24 (25%) were administered thoracic RT.…”

Section: Discussionmentioning

confidence: 99%

“…Of the 98 patients registered in the KEYNOTE‐001 phase I trial, Shaverdian et al reported that the duration of progression‐free survival (PFS) with pembrolizumab was significantly longer in patients previously administered RT than in those not treated with RT . Fiorica et al also reported that nivolumab treatment after hypofractionated RT improved the outcome in 35 patients with pretreated or metastatic NSCLC . These results suggest that previous RT clinically improves tumor response and immune reaction to ICIs, such as nivolumab or pembrolizumab.…”

Section: Introductionmentioning

confidence: 99%

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Radiotherapy is an independent prognostic marker of favorable prognosis in non‐small cell lung cancer patients after treatment with the immune checkpoint inhibitor, nivolumab

et al. 2019

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Background It remains unclear why radiation clinically provides a synergistic effect when combined with immune checkpoint inhibitors such as nivolumab. The purpose of our study was to retrospectively evaluate whether the therapeutic efficacy of nivolumab is improved as a result of a history of radiotherapy (RT) in patients with previously treated advanced non‐small cell lung cancer (NSCLC). Methods From February 2016 to December 2017, 124 consecutive patients were administered nivolumab for pretreated advanced NSCLC. The patients were divided into RT and non‐RT groups. Results Sixty‐six (53%) of the 124 patients had been administered RT before the initiation of nivolumab, 52 (42%) received extracranial RT, and 40 (32%) were treated with thoracic RT. The median number of nivolumab cycles was 4 (range: 1–43). The overall response rate (ORR) and disease control rate (DCR) of nivolumab in all patients were 28.0% and 58.4%, respectively. The ORR (36.4%) was significantly higher in patients who had received previous RT than in patients who had not received any RT (19%). The therapeutic efficacy of nivolumab was particularly noteworthy in patients with non‐adenocarcinoma and squamous cell carcinoma histology administered extracranial RT, with ORRs of 48.3% and 52.6%, and DCRs of 87.1% and 84.2%, respectively. Conclusion Previous RT was an independent prognostic marker of favorable prognosis after nivolumab administration and improved the response rate to nivolumab treatment. Previous RT was clinically identified to have a synergistic effect with nivolumab treatment, increasing the response rate and improving the outcome of patients with advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Radiotherapy is an independent prognostic marker of favorable prognosis in non‐small cell lung cancer patients after treatment with the immune checkpoint inhibitor, nivolumab

et al. 2019

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“…Preclinical studies showed that conventional therapy including the radiotherapy and chemotherapy could kill tumor cells and induce PD‐L1 expression on tumor cells . Fiorica and colleagues reported that immune checkpoint inhibitors plus radiotherapy gained both OS and PFS benefit with tolerated toxicities in patients of NSCLC . Several studies demonstrated that immune checkpoint inhibitors alone or plus chemotherapy could improve tumor response and prolong survival in both male and female patients in NSCLC .…”

Section: Discussionmentioning

confidence: 99%

“…38,39 Fiorica and colleagues reported that immune checkpoint inhibitors plus radiotherapy gained both OS and PFS benefit with tolerated toxicities in patients of NSCLC. 40 Several studies demonstrated that immune checkpoint inhibitors alone or plus chemotherapy could improve tumor response and prolong survival in both male and female patients in NSCLC. 21,22,26 However, other studies showed that immune checkpoint inhibitors alone or plus chemotherapy had no obvious survival benefit in both men and women in NSCLC.…”

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confidence: 99%

Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non‐small cell lung cancer

et al. 2019

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Immune checkpoint inhibitors (ICIs) have shown promising efficacy in the treatment of non‐small cell lung cancer (NSCLC). Sex‐associated dimorphism in immune system response is acknowledged, but the effect of patients’ sex on efficacy of ICIs as treatment in NSCLC still remains controversial. The present study was conducted to investigate the difference in efficacy of NSCLC patients receiving immune checkpoint inhibitors according to the sex. A total of 9583 patients involved 6567 men and 3016 women with advanced lung cancer from 15 randomized controlled trials were included in this study. An overall survival (OS) benefit of immune checkpoint inhibitors was illustrated in both male (HR 0.76, 95% CI 0.71‐0.82) and female (HR 0.73, 95% CI 0.58‐0.91) patients, and a progression‐free survival (PFS) benefit was also found in both men (HR 0.67, 95% CI 0.58‐0.77) and women (HR 0.73, 95% CI 0.56‐0.95) in NSCLC. Both PD‐1/PD‐L1 inhibitors alone and PD‐1/PD‐L1 plus chemotherapy significantly improved the OS and PFS in male patients. Whereas in females, PD‐1 inhibitors or monotherapy significantly benefited the OS but not the PFS, PD‐L1 inhibitors or combination therapy significantly prolonged the PFS but not the OS. No survival benefit was found in both male and female patients from the CTLA‐4 inhibitors. The current study indicated that the magnitude of survival benefit is sex‐dependent and male patients seemed to obtain more consistent and favorable outcomes from ICIs than women patients in NSCLC.

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Gene signature based on B cell predicts clinical outcome of radiotherapy and immunotherapy for patients with lung adenocarcinoma

et al. 2020

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Immune Checkpoint Inhibitor Nivolumab and Radiotherapy in Pretreated Lung Cancer Patients

Abstract: In conclusion, RT and nivolumab can be combined, obtaining a benefit in overall survival and progression-free survival, without an increase in acute toxicities in pretreated advanced NSCLC patients. Prospective studies are needed to confirm these results.

Cited by 57 publications

References 21 publications

Radiotherapy is an independent prognostic marker of favorable prognosis in non‐small cell lung cancer patients after treatment with the immune checkpoint inhibitor, nivolumab

Radiotherapy is an independent prognostic marker of favorable prognosis in non‐small cell lung cancer patients after treatment with the immune checkpoint inhibitor, nivolumab

Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non‐small cell lung cancer

Gene signature based on B cell predicts clinical outcome of radiotherapy and immunotherapy for patients with lung adenocarcinoma

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