Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH)

Peters, Solange; Gettinger, Scott; Johnson, Melissa L.; Jänne, Pasi A.; Garassino, Marina Chiara; Christoph, Daniel C.; Toh, Chee-Keong; Rizvi, Naiyer A.; Chaft, Jamie E.; Costa, Enric Carcereny; Patel, Jyoti D.; Chow, Laura Q.M.; Koczywas, Marianna; Ho, Cheryl; Früh, Martin; Heuvel, Michel van den; Rothenstein, J.; Reck, Martin; Paz‐Ares, Luis; Shepherd, Frances A.; Kurata, Takeshi; Li, Zhengrong; Qiu, Jack Linchuan; Kowanetz, Marcin; Mocci, Simonetta; Shankar, Geetha; Sandler, Alan; Felip, Enriqueta

doi:10.1200/jco.2016.71.9476

Cited by 343 publications

(309 citation statements)

References 26 publications

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“…This has been confirmed in a recent meta-analysis [78] and corroborated in other studies [79]. In the BIRCH trial, ORRs were lower in previously-treated EGFR mutant-positive patients treated with atezolizumab compared with EGFRwild-type patients [42]. In the JAVELIN solid tumor trial, no confirmed responses to avelumab were reported in patients (n = 10) with EGFR mutations or ALK translocations [45].…”

Section: Mutational Status Egfr and Alksupporting

confidence: 54%

“…Following positive results in two Phase II trials (POPLAR and BIRCH) [42,43], atezolizumab was compared with docetaxel in a Phase III study (OAK) in unselected patients who had received up to two previous chemotherapy regimens, including at least one platinum-based therapy. OS was significantly improved in the atezolizumab treatment group compared with the docetaxel group.…”

Section: Pd-l1 Inhibitorsmentioning

confidence: 99%

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Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided.

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Section: Mutational Status Egfr and Alksupporting

confidence: 54%

Section: Pd-l1 Inhibitorsmentioning

confidence: 99%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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“…Peters and colleagues[30, 31] have recently reported the results of the “BIRCH” study, a phase II single-arm trial of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic PD-L1-selected NSCLC. Patients with PD-L1 positive tumors (TC2/3 and/or IC2/3) and without brain metastasis were eligible.…”

Section: Clinical Efficacymentioning

confidence: 99%

Atezolizumab for the treatment of non-small cell lung cancer

Santini

Rudin

2017

Expert Review of Clinical Pharmacology

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Introduction The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas Covered This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology. We discuss the discovery of PD-L1 and PD-L2 while highlight the potential differences in targeting PD-L1 versus PD-1. In addition, we briefly summarized the available pre-clinical and clinical data of atezolizumab use in NSCLC. A special section covers the challenges of PD-L1 immunohistochemistry assay. Expert commentary PD-1:PD-L1 blockade has taken the lead in the immunotherapeutics field and represents the backbone of developing combination immunotherapies. Atezolizumab represents a step forward in the treatment of advanced NSCLC, nonetheless PD1:PD-L1 blockade in early-stage lung cancer is still a matter of debate.

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“…These agents have produced durable clinical responses and antitumor activity in Phase I trials, leading to subsequent randomized Phase II and III trials that demonstrated significant improvements in overall survival when compared with cytotoxic chemotherapy alone [12][13][14][15][16]. These studies have established PD-1/PD-L1 pathway blockade as a powerful new line of therapy for patients with advanced NSCLC following progression after platinum-based therapy [9,11].…”

mentioning

confidence: 99%

Can radiotherapy potentiate the effectiveness of immune checkpoint inhibitors in lung cancer?

et al. 2017

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Systemic therapy including platinum-based chemotherapy and targeted therapy has been a mainstay of treatment for the majority of patients with metastatic non-small-cell lung cancer (NSCLC). Recent breakthroughs in immune checkpoint blockade, along with a deeper understanding of tumor immune biology, have led to a paradigm shift in the standard of care for cancer treatment. By activating the immune system to recognize and eliminate cancer, immune checkpoint blockade has the potential to elicit durable responses and augment survival outcomes for a subset of patients [1,2]. In addition, the ability of radiotherapy to induce an immunogenic response and neutralize the immune-suppressive effects of the tumor microenvironment, uniquely positions it as a synergistic tool at the center of emerging multimodal therapies utilizing immune checkpoint blockade [3][4][5][6][7].Immune checkpoint inhibitors of the PD-1/PD-L1 pathway have emerged as a promising new therapeutic strategy [8][9][10][11]. These agents have produced durable clinical responses and antitumor activity in Phase I trials, leading to subsequent randomized Phase II and III trials that demonstrated significant improvements in overall survival when compared with cytotoxic chemotherapy alone [12][13][14][15][16]. These studies have established PD-1/PD-L1 pathway blockade as a powerful new line of therapy for patients with advanced NSCLC following progression after platinum-based therapy [9,11]. Despite unprecedented improvements in clinical outcomes, less than 20% of patients respond to anti-PD-1/PD-L1 agents, necessitating strategies that explore combined treatment modalities in order to extend the benefits of immune checkpoint blockade to a broader patient population. The Phase II KEYNOTE-021 trial (NCT02039674), for example, evaluated the treatment of pembrolizumab in combination with pemetrexed and carboplatin and found significantly prolonged progression-free survival (median 13.0 vs 8.9 months; 6-month survival 92% for both arms) for patients with previously untreated metastatic nonsquamous NSCLC [17]. This trial, as well as the KEYNOTE-024 trial (NCT02142738), has served to bring PD-1 inhibition into the front-line setting for NSCLC [13].Radiation has become known for its abscopal effect in lung cancer. There are many compelling reasons to combine radiotherapy with checkpoint inhibition in the treatment of NSCLC. Radiation affects the immune system in many ways including release of neoantigens, upregulation of PD-L1 on tumor cells, recruitment of T cells to the tumor bed and neutralization of the immune-suppressive effects of the tumor microenvironment. Over 60% of patients with NSCLC require radiotherapy at least once during their course of treatment, and radiotherapy used in combination with immune checkpoint blockade has shown potential in preclinical and early clinical studies [3,6,7,18]. A Phase II trial of consolidation pembrolizumab initiated 1-2 months after concurrent chemoradiation demonstrated safety of such treatment [19]. In fact, in May 2017...

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Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH)

Cited by 343 publications

References 26 publications

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

Atezolizumab for the treatment of non-small cell lung cancer

Can radiotherapy potentiate the effectiveness of immune checkpoint inhibitors in lung cancer?

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