122TiP Phase III study of durvalumab with SBRT for unresected stage I/II, lymph-node negative NSCLC (PACIFIC-4/RTOG 3515)

Robinson, C.G.; Xing, Lijie; Tanaka, Hiroshi; Tasaka, S.; Badiyan, Shahed N.; Nasrallah, Haitam; Biswas, Tithi; Shtivelband, Mikhail; Schuette, Wolfgang; Shi, Anhui; Hepner, A.; Barrett, Karen; Rigas, James R.; Jiang, Haiyi; Lin, Song-Chang

doi:10.1016/j.annonc.2022.02.149

Cited by 2 publications

(3 citation statements)

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“…MPR in the combination group led to an impressive CR rate of 50%. The role of combining SBRT and immunotherapy in very early staged NSCLC is currently being investigated in multiple ongoing trials (257)(258)(259)(260).…”

Section: Combining An Ici With Chemoradiation In Earlier Stage Nsclcmentioning

confidence: 99%

Mechanistic rationales for combining immunotherapy with radiotherapy

Chi

Nguyen

2023

Front. Immunol.

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Immunotherapy consisted mainly of immune checkpoint inhibitors (ICIs) has led to significantly improved antitumor response. However, such response has been observed only in tumors possessing an overall responsive tumor immune micro-environment (TIME), in which the presence of functional tumor-infiltrating lymphocytes (TILs) is critical. Various mechanisms of immune escape from immunosurveillance exist, leading to different TIME phenotypes in correlation with primary or acquired resistance to ICIs. Radiotherapy has been shown to induce antitumor immunity not only in the irradiated primary tumor, but also at unirradiated distant sites of metastases. Such antitumor immunity is mainly elicited by radiation’s stimulatory effects on antigenicity and adjuvanticity. Furthermore, it may be significantly augmented when irradiation is combined with immunotherapy, such as ICIs. Therefore, radiotherapy represents one potential therapeutic strategy to restore anti-tumor immunity in tumors presenting with an unresponsive TIME. In this review, the generation of anti-tumor immunity, its impairment, radiation’s immunogenic properties, and the antitumor effects of combining radiation with immunotherapy will be comprehensively discussed.

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Section: Combining An Ici With Chemoradiation In Earlier Stage Nsclcmentioning

confidence: 99%

Mechanistic rationales for combining immunotherapy with radiotherapy

Chi

Nguyen

2023

Front. Immunol.

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“…At present, three randomized trials evaluating the efficacy of adding an ICI to SBRT in N0 ES NSCLC are ongoing. Among them, PACIFIC-4/RTOG 3515 (NCT03833154) and KEYNOTE (KN)-867 (NCT03924869) are placebo-controlled and do not select patients based on high-risk features [65][66][67]. PACIFIC-4 was initially designed to have patients receive adjuvant Durvalumab or placebo for two years after SBRT over 3, 4, 5, or 8 fractions, but was then modified to concurrent administration of Durvalumab or placebo with SBRT for two years [65,66].…”

Section: Clinical Evidence For Combining Sbrt With Immune Checkpoint ...mentioning

confidence: 99%

“…Among them, PACIFIC-4/RTOG 3515 (NCT03833154) and KEYNOTE (KN)-867 (NCT03924869) are placebo-controlled and do not select patients based on high-risk features [65][66][67]. PACIFIC-4 was initially designed to have patients receive adjuvant Durvalumab or placebo for two years after SBRT over 3, 4, 5, or 8 fractions, but was then modified to concurrent administration of Durvalumab or placebo with SBRT for two years [65,66]. A separate EGFR-mutant cohort also exists in PACIFIC-4, which will be assigned to adjuvant Osimertinib for three years after SBRT.…”

Section: Clinical Evidence For Combining Sbrt With Immune Checkpoint ...mentioning

confidence: 99%

Rationale for Combing Stereotactic Body Radiation Therapy with Immune Checkpoint Inhibitors in Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

Chi

Nguyen

2022

Cancers

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Stereotactic body radiation therapy (SBRT) has been widely adopted as an alternative to lobar resection in medically inoperable patients with lymph-node negative (N0) early-stage (ES) non-small cell lung cancer (NSCLC). Excellent in-field local control has been consistently achieved with SBRT in ES NSCLC ≤ 3 cm in size. However, the out-of-field control following SBRT remains suboptimal. The rate of recurrence, especially distant recurrence remains high for larger tumors. Additional systemic therapy is warranted in N0 ES NSCLC that is larger in size. Radiation has been shown to have immunomodulatory effects on cancer, which is most prominent with higher fractional doses. Strong synergistic effects are observed when immune checkpoint inhibitors (ICIs) are combined with radiation doses in SBRT’s dose range. Unlike chemotherapy, ICIs can potentiate a strong systemic response outside of the irradiated field when combined with SBRT. Together with their less toxic nature, ICIs represent a very suitable class of systemic agents to be combined with SBRT when treating ES NSCLC with high-risk features, such as larger tumor size. In this review, we describe the rationale and emerging evidence, as well as ongoing investigations in this area.

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122TiP Phase III study of durvalumab with SBRT for unresected stage I/II, lymph-node negative NSCLC (PACIFIC-4/RTOG 3515)

Cited by 2 publications

References 0 publications

Mechanistic rationales for combining immunotherapy with radiotherapy

Mechanistic rationales for combining immunotherapy with radiotherapy

Rationale for Combing Stereotactic Body Radiation Therapy with Immune Checkpoint Inhibitors in Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

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