Impact of Radiotherapy on the Efficacy and Toxicity of anti-PD-1 Inhibitors in Metastatic NSCLC

Samuel, Evangeline; Lie, Gabrielle; Balasubramanian, Adithya; Hiong, Alison; So, Yeojeong; Voskoboynik, Mark; Moore, Miranda; Shackleton, Mark; Haydon, Andrew; John, Thomas; Mitchell, Paul; Markman, Ben; Briggs, Peter; Parakh, Sagun

doi:10.1016/j.cllc.2020.06.001

Cited by 15 publications

(19 citation statements)

References 26 publications

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“…Inhibitors (ICI) alone (Samuel et al 2020 ; Theelen et al 2019 ). The reason for the inconsistent outcomes may be the single-site irradiation in these studies.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer

Yin

Zhao

et al. 2021

J Cancer Res Clin Oncol

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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.

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“…Inhibitors (ICI) alone (Samuel et al 2020 ; Theelen et al 2019 ). The reason for the inconsistent outcomes may be the single-site irradiation in these studies.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer

Yin

Zhao

et al. 2021

J Cancer Res Clin Oncol

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“…The current body of clinical data suggests radiotherapy can enhance the efficacy of ICIs with an acceptable safety profile in patients with metastatic NSCLC ( 26 , 142 , 180 ). A secondary analysis of the KEYNOTE-001 trial conducted by Shaverdian et al suggested a prolongation of PFS and OS in patients who received both thoracic radiotherapy and pembrolizumab compared with those with no previous thoracic radiotherapy, and no statistically significant differences in the incidence of pulmonary toxicity of any grade were observed between the two groups (63% vs. 40%, P=0.052) ( 142 ).…”

Section: Combining Radiation and Icismentioning

confidence: 99%

“…A secondary analysis of the KEYNOTE-001 trial conducted by Shaverdian et al suggested a prolongation of PFS and OS in patients who received both thoracic radiotherapy and pembrolizumab compared with those with no previous thoracic radiotherapy, and no statistically significant differences in the incidence of pulmonary toxicity of any grade were observed between the two groups (63% vs. 40%, P=0.052) ( 142 ). A recent retrospective study involving 269 metastatic NSCLC patients treated with nivolumab or pembrolizumab included 102 patients who underwent radiotherapy within 3 months of initiation of anti-PD-1 therapy or subsequently during anti-PD-1 therapy ( 180 ), and the addition of radiotherapy to anti-PD-1 therapy was not associated with increased toxicity. The efficacy and safety of ICIs in combination with radiation has also been explored in several prospective trials.…”

Section: Combining Radiation and Icismentioning

confidence: 99%

International consensus on radiotherapy in metastatic non-small cell lung cancer

Zhu¹,

Ni²,

Cai³

et al. 2022

Transl Lung Cancer Res

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Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multi-disciplinary management of the disease.Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide.Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established. Conclusions:In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.

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“…Anti-PD-1 therapy enhances the efficacy of radiotherapy in metastatic gastric cancer treatment by increasing the CD8 + T cell/effector regulatory T cell ratio in TILs (160). Another study showed that patients with metastatic NSCLC treated with nivolumab or pembrolizumab+radiotherapy did not have increased grade 3/4 immune-related adverse events (161). The combination of chemotherapy and radiotherapy with PD-1/PD-L1 inhibitors induces lasting immune response in treatment of tumors when other treatment strategies fail.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

A combination of PD‑1/PD‑L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)

et al. 2021

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Impact of Radiotherapy on the Efficacy and Toxicity of anti-PD-1 Inhibitors in Metastatic NSCLC

Cited by 15 publications

References 26 publications

Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer

Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer

International consensus on radiotherapy in metastatic non-small cell lung cancer

A combination of PD‑1/PD‑L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)

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