IMpower150: An exploratory analysis of efficacy outcomes in patients with EGFR mutations

Mok, Tony; Socinski, Mark A.; Reck, M.; Jotte, Robert M.; Lim, Diane S. W.; Cappuzzo, Federico; Orlandi, F.; Stroyakovskiy, Daniil; Nogami, Naoyuki; Rodríguez-Abreu, Delvys; Moro-Siblot, D.; Thomas, Christian A.; Finley, Gene Grant; Lee, A.; Shankar, Geetha; Kowanetz, Marcin; Lin, W.; Nishio, Makoto

doi:10.1093/annonc/mdz063.002

Cited by 14 publications

(14 citation statements)

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“…In addition, clinical trials involving combination immunotherapy of anti-PD-1/PD-L1 Abs with other modalities have demonstrated the promising efficacy of this regimen against some cancers (25,26). Among these the combination of ICIs with antiangiogenic agents, including an anti-VEGF Ab, bevacizumab, has been expected and has shown durable efficacy in several cancers, including advanced hepatocellular carcinoma (33)(34)(35)(36)(37). We previously reported that therapy with anti-VEGF agents, including bevacizumab or inhibitors, increased the accumulation of fibrocytes in tumors in mice and humans (21).…”

Section: Discussionmentioning

confidence: 99%

Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes

Afroj

Mitsuhashi

Ogino

et al. 2021

The Journal of Immunology

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Fibrocytes, a distinct population of collagen-producing, monocyte-derived cells, are involved in wound healing as well as fibrotic diseases. Recently, fibrocytes have been revealed to play a role in the tumor microenvironment, particularly under antiangiogenic therapy. In addition, combination cancer immunotherapy with immune checkpoint inhibitor and antiangiogenic agents have been developed for various cancers in the clinical setting, although the immunological background is not clear. In the current study, we aimed to determine the function of fibrocytes in tumor immunity induced by immune checkpoint inhibitor therapy. Human and murine fibrocytes were generated from PBMCs and lungs, respectively. The expression of costimulatory and inhibitory molecules on fibrocytes was examined by flow cytometry. The stimulation of CD8 + T cells by fibrocytes was examined in MLRs with a 3 Hthymidine incorporation assay. Fibrocytes expressed CD80 low and CD86 high as a costimulatory molecule, and expressed PD-L1 high , but not PD-L2, as a coinhibitory molecule. Without any stimulation, fibrocytes strongly enhanced the proliferation of CD8 + T cells in mice and humans. Treatment with anti-CD86 and -CD54 Abs inhibited the growth of CD8 + T cells induced by fibrocytes. Anti-PD-L1 Ab further enhanced the proliferation of CD8 + T cells, even in the OVA-specific MLR with OT-1Rag 2/2 mice. Importantly, fibrocytes derived from PBMCs of patients with lung adenocarcinoma or murine MC38 tumors augmented the proliferation of CD8 + T cells with PD-L1 blockade. These results suggest that fibrocytes infiltrating tumor sites may play a role in the antitumor immunity mediated by CD8 + T cells when the activity is further enhanced by PD-L1/PD-1 blockade.

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Section: Discussionmentioning

confidence: 99%

Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes

Afroj

Mitsuhashi

Ogino

et al. 2021

The Journal of Immunology

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“…Emerging clinical data also point to synergy between angiogenesis inhibitors and immune checkpoint blockers in patients with NSCLC [21]. For example, the Phase III IMpower150 trial provided evidence that the efficacy of atezolizumab is augmented by the anti-VEGF agent bevacizumab, when these two agents are combined with chemotherapy for first-line treatment of EGFR-mutant non-squamous NSCLC [24]. Phase I studies have also shown activity of ramucirumab plus either pembrolizumab or durvalumab in previously treated advanced NSCLC [31,32], and nivolumab plus bevacizumab as maintenance therapy for non-squamous NSCLC following first-line chemotherapy [33].…”

Section: Tablementioning

confidence: 99%

“…Of particular relevance, high vascular endothelial growth factor (VEGF) levels are implicated in the development of an immunosuppressive tumor microenvironment (TME), and, therefore, could foster resistance to immunotherapies while sensitizing to anti-angiogenic treatments [20]. Further support is provided by preclinical activity of combinations of anti-angiogenic and immunotherapeutic agents, along with emerging data indicating clinical synergism between these two therapeutic strategies [21,23,24].…”

Section: Introductionmentioning

confidence: 99%

Non-interventional LUME-BioNIS study of nintedanib plus docetaxel after chemotherapy in adenocarcinoma non-small cell lung cancer: A subgroup analysis in patients with prior immunotherapy

et al. 2020

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To evaluate the effectiveness and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) previously treated with both chemo-and immunotherapy. Materials and methods: LUME-BioNIS is a European, prospective, multicenter, non-interventional study of patients with advanced adenocarcinoma NSCLC, who initiated nintedanib plus docetaxel after first-line chemotherapy in routine practice according to the approved nintedanib EU label. The primary objective is to explore whether molecular biomarkers can predict overall survival (OS). Information on clinical or radiologic progression and death, and adverse drug reactions (ADRs)/fatal adverse events (AEs) was collected during follow-up. Here, we report a subgroup analysis evaluating outcomes in immunotherapy-pretreated patients. Results: Of 260 enrolled patients, 67 (25.8%) had prior immunotherapy and were included in this subgroup analysis. Prior immunotherapy was administered in first-line in 20 patients (29.9%; combined with chemotherapy in 4 patients [6.0%]) and later-lines in 47 patients (70.1%), and most commonly comprised nivolumab (39 patients; 58.2%), atezolizumab (14 patients; 20.9%) and pembrolizumab (11 patients; 16.4%). Nintedanib plus docetaxel was given in second-line in 10 patients (14.9%) and in later-lines in 57 patients (85.1%). Median OS was 8.8 months (95% confidence interval [CI]: 7.0-11.5) and median progression-free survival (PFS) was 4.6 months (95% CI: 3.5-5.7). Among 55 patients with available data, rates of objective response and disease control were 18.2% and 78.2%, respectively. In 65 patients evaluable for safety, the most common on-treatment ADRs/ AEs were malignant neoplasm progression (19 patients; 29.2%), diarrhea (21 patients; 32.3%) and nausea (10 patients; 15.4%). Conclusions: Used according to the approved nintedanib label in routine practice, nintedanib plus docetaxel demonstrated clinical effectiveness, with no unexpected safety findings, in patients with prior chemotherapy and

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“…An improvement in response rate translated to an improvement in mOS in driver mutation wild‐type patients in the quadruplet vs bevacizumab + chemotherapy (19.2 vs 14.7 months, HR 0.78, P = .002). This was the first study that showed improved OS with an ICB for patients who had progressed following targeted therapy for EGFR‐mutated tumours (mOS NR vs 17.5, HR 0.3,9 95% CI 0.14–1.07 for atezolizumab, bevacizumab, carboplatin and paclitaxel vs bevacizumab, carboplatin and paclitaxel, P‐value not provided), 60 suggesting the quadruplet Impower 150 regimen preferential in this post‐EGFR space. Please refer to Table 1 for descriptors of all pivotal trials leading to FDA registration for ICBs in melanoma and NSCLC.…”

Section: Effect On Clinical Practicementioning

confidence: 96%

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

Navani

Graves

Westhuizen

2020

Brit J Clinical Pharma

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Immune checkpoint blockade has transformed outcomes across solid organ tumours. Monoclonal antibodies targeting the negative inhibitory cytotoxic T lymphocyte‐associated protein 4 and programmed‐death 1/programmed death‐ligand 1 axis can lead to deep and durable responses across several tumour streams in the advanced setting. This immunotherapy approach is increasingly used earlier in the treatment paradigm. A rapidly evolving regulatory, reimbursement and drug development landscape has accompanied this novel class of immunotherapy. Unfortunately, only a small proportion of patients respond meaningfully to these agents. Here we review how the underlying tumoural genomic, histological and immunological characteristics interact within various patient phenotypes, leading to variations in response to checkpoint blockade. Concurrently, we outline the clinical trial and real‐world evidence that allows for appropriate selection of agent, dose and schedule in solid organ malignancies. An exploration of current trends in basic and translational research in immune checkpoint blockade accompanies a commentary on future clinical directions for checkpoint blockade in oncology.

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IMpower150: An exploratory analysis of efficacy outcomes in patients with EGFR mutations

Cited by 14 publications

References 0 publications

Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes

Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes

Non-interventional LUME-BioNIS study of nintedanib plus docetaxel after chemotherapy in adenocarcinoma non-small cell lung cancer: A subgroup analysis in patients with prior immunotherapy

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

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