Clinical Outcomes in Patients With Metastatic Lung Cancer Treated With PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy

Hwang, William L.; Niemierko, Andrzej; Hwang, Katie L.; Hubbeling, Harper; Schapira, Emily; Gainor, Justin F.; Keane, Florence K.

doi:10.1001/jamaoncol.2017.3808

Cited by 84 publications

(77 citation statements)

References 8 publications

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“…According to our analyses, IRAEs were associated with better PFS (P = 0.038) and a trend toward longer OS (P = 0.06), in agreement with those of Hwang et al, who also found that grade >2 IRAEs in NSCLC patients treated with thoracic radiotherapy and anti-PD-1 were associated with longer survival. 24 That relationship was also described in NSCLC 31 and melanoma patients. 32 The synergy of radiotherapy with anti-PD-L1 efficacy remains controversial.…”

Section: Discussionmentioning

confidence: 76%

“…This good tolerance of the combination of radiotherapy and anti-PD-1 has been found previously. 13,15,16,23,24 In a retrospective analysis of 163 patients with advanced NSCLCs and brain metastases, rates of all-grade AEs and grade ≥3 AEs did not differ significantly between patients, who received intracranial RT and were treated with or without anti-PD-1 (grade ≥3 AEs: 8% of anti-PD-1-naïve patients vs 9% of anti-PD-1-treated patients with SRS, P = 1.00; and 8% of anti-PD-1-naïve patients vs 0% of anti-PD-1-treated patients with wholebrain RT, P = 0.71). In addition, AE rates did not differ according to the timing of anti-PD-1 administration with respect to irradiation.…”

Section: Discussionmentioning

confidence: 99%

“…23 Our results also agreed with the Keynote-001 trial subset analysis of irradiated patients 26 and other retrospective series. 24,27 Only one patient experimented a grade III immune-related adverse event directly correlated to the irradiation field (immune esophagitis after a cervical irradiation). This kind of secondary effect could be related to a T-cell infiltration of the esophagus according to the hypothesis proposed by Myers and Du, after having exposed murine preclinical model to the therapeutic combination.…”

Section: Discussionmentioning

confidence: 99%

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Safety of combined PD‐1 pathway inhibition and radiation therapy for non‐small‐cell lung cancer: A multicentric retrospective study from the GFPC

et al. 2018

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IntroductionRandomized prospective studies on patients with metastatic non‐small‐cell lung cancers (NSCLCs) showed that anti‐programmed death‐1 (PD‐1) agents notably improved 2‐year overall survival (OS) rates, compared to docetaxel. NSCLC patients now receive nivolumab and irradiation, concurrently or not. However, little is known about the safety of this combination, even though the preclinical model suggested a possible synergic effect. We analyzed NSCLC patients treated with radiotherapy and nivolumab according to former's timing.MethodsWe retrospectively reviewed records of a large series of metastatic NSCLC patients from three French centers, irradiated during the 6 months preceding, concomitantly, or 3 months after nivolumab administration to assess nivolumab tolerance and outcomes.ResultsAmong 104 patients included (37 women; 67 men; median age 60.3 years; 67% with performance status <2; 93.2% were current or past smokers) and their 144 intra‐ or extracranial irradiation courses, any‐grade adverse events (AEs) were observed in 62 (59.6%), with 10 (9.6%) experiencing at least one grade 3/4 toxicity and 9 (8.7%) at least one grade 3/4 immune‐related AE (IRAE). Respective 1‐ and 2‐year OS rates were 48.8% and 29.1%, while 1‐ and 2‐year progression‐free survival (PFS) rates were 20.9% and 10.1%. PFS was significantly better for patients with IRAE(s) (P = 0.038) than those without and a trend toward better OS (P = 0.06). Delivering radiation before or during/after nivolumab administration was not associated with better OS or PFS.ConclusionRadiotherapy delivered during the 6 months before, during, or the three months following nivolumab for NSCLCs was not associated with an increased risk of severe or unexpected toxicities.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Safety of combined PD‐1 pathway inhibition and radiation therapy for non‐small‐cell lung cancer: A multicentric retrospective study from the GFPC

et al. 2018

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“…These results are consistent with those of recent studies evaluating the toxicity of thoracic RT, in which the addition of ICI therapy was not observed to significantly increase treatment-related AEs. 28,29 A recent subanalysis of KEYNOTE-001 noted improved efficacy of pembrolizumab among patients receiving radiation before immunotherapy, supporting the notion that clinically relevant immune synergy between RT and ICI therapy may occur. 28 To investigate whether the frequency and/or spectrum of RT-related toxicities may differ depending on the relative timing and sequencing of RT with ICI therapy, we conducted additional subgroup analyses.…”

Section: Discussionmentioning

confidence: 96%

Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non–Small Cell Lung Cancer

Hubbeling

Schapira

Horick

et al. 2018

Journal of Thoracic Oncology

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“…Concerning conventional TRT, based on retrospective data, irAEs such as pneumonitis were demonstrated not to be common in metastatic lung cancer patients treated using both ICIs and TRT [98,99]. However, other studies have suggested a link between prior radiation pneumonitis and increased frequency of either radiation pneumonitis or ICI-P after nivolumab exposure [100][101][102].…”

Section: Radiation Pneumonitis or Ici-p In Cancer Patients Receivingmentioning

confidence: 99%

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

et al. 2019

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Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines.

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Clinical Outcomes in Patients With Metastatic Lung Cancer Treated With PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy

Cited by 84 publications

References 8 publications

Safety of combined PD‐1 pathway inhibition and radiation therapy for non‐small‐cell lung cancer: A multicentric retrospective study from the GFPC

Safety of combined PD‐1 pathway inhibition and radiation therapy for non‐small‐cell lung cancer: A multicentric retrospective study from the GFPC

Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non–Small Cell Lung Cancer

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

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