IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain

Nogami, Naoyuki; Barlési, Fabrice; Socinski, Mark A.; Reck, Martin; Thomas, Christian A.; Cappuzzo, Federico; Mok, Tony; Finley, Gene Grant; Aerts, Joachim; Orlandi, F; Moro-Sibilot, Denis; Jotte, Robert M.; Stroyakovskiy, Daniil; Villaruz, Liza C.; Rodríguez-Abreu, Delvys; Lim, Darren Wan-Teck; Merritt, David M.; Coleman, Shelley; Lee, Anthony; Shankar, Geetha; Yu, Wei; Bara, Ilze; Nishio, Makoto

doi:10.1016/j.jtho.2021.09.014

Cited by 166 publications

(113 citation statements)

References 46 publications

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“…The results show that improved survival was achieved in patients treated with ABCP compared to those given BCP in the intention-to-treat population or those with baseline liver metastases [81]. Recently, final OS analyses were presented for EGFR mutations and liver or brain metastases subgroups in the phase III IMpower150 study evaluating ABCP or ACP versus BCP [82]. This final exploratory analysis showed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with prior TKI failures, and with liver metastases, although these results should be interpreted with caution.…”

Section: Combined Anti-angiogenic Therapymentioning

confidence: 99%

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Progress, Challenges, and Prospects

Tang

Qin

et al. 2022

Cells

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Non-small cell lung cancer is one of the most common types of malignances worldwide and the main cause of cancer-related deaths. Current treatment for NSCLC is based on surgical resection, chemotherapy, radiotherapy, and targeted therapy, with poor therapeutic effectiveness. In recent years, immune checkpoint inhibitors have applied in NSCLC treatment. A large number of experimental studies have shown that immune checkpoint inhibitors are safer and more effective than traditional therapeutic modalities and have allowed for the development of better guidance in the clinical treatment of advanced NSCLC patients. In this review, we describe clinical trials using ICI immunotherapies for NSCLC treatment, the available data on clinical efficacy, and the emerging evidence regarding biomarkers.

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Section: Combined Anti-angiogenic Therapymentioning

confidence: 99%

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Progress, Challenges, and Prospects

Tang

Qin

et al. 2022

Cells

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“…In IMpower150 trial ( 83 ), patients were randomized 1:1:1 to receive atezolizumab + bevacizumab + carboplatin/paclitaxel (ABCP), atezolizumab + carboplatin/paclitaxel(ACP), or bevacizumab + carboplatin/paclitaxel (BCP). With a good tolerance, significantly improved PFS and OS were observed in the ABCP group compared with the BCP group for metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status.…”

Section: Combination Strategy For Nsclc-bmsmentioning

confidence: 99%

Navigate Towards the Immunotherapy Era: Value of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Brain Metastases

2022

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Brain metastases (BMs) in non-small-cell lung cancer (NSCLC) patients are associated with significant morbidity and poor prognosis. Immune checkpoint inhibitors (ICIs) have resulted in a paradigm shift in the management of advanced NSCLC. However, the value of ICIs in NSCLC patients with BMs remains unclear because patients with BMs are routinely excluded in numerous prospective trials on ICIs. Here, starting from the mechanisms of ICIs for BMs, we will reveal the value of ICIs by reviewing the efficacy and adverse effects of ICIs monotherapy as well as promising combination strategies, such as combinations with chemotherapy, radiotherapy, and anti-angiogenic drugs, etc. In addition, the methods of patient selection and response assessment will be summarized to assist clinical practice and further studies.

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“… 23 OS was NE (95% CI=NE–NE) with ABCP (N=26 of 400) vs 17.5 months (95% CI=11.7–NE) with BCP (N=32 of 400) which resulted in a HR of 0.31 (95% CI=0.11–0.83). However, although the updated analysis from the IMpower150 study 24 showed that patients with EGFR mutations had numerically longer OS with the ABCP arm with a median of 26.1 months as compared to the BCP arm which reported a median of 20.3 months, the HR point estimate was 0.91 for ABCP vs BCP (95% CI=0.53–1.59), which may be a reflection of the limitations of sub-group analysis with a small number of patients or the results of patients crossing over to receive atezolizumab. Furthermore, no OS benefit was seen for atezolizumab + carboplatin + paclitaxel (ACP) compared with BCP in patients with sensitizing EGFR mutations who had received prior TKI therapy (21.4 vs 20.3 months; HR=1.16; 95% CI=0.71–1.89), hinting at the role of bevacizumab perhaps having synergistic effects to the combination of chemotherapy and ICI in this setting.…”

Section: “Off-target” Approachmentioning

confidence: 99%

ORIENT-31 as the Sakigake “Charging Samurai” Born of IMpower150 but Will MARIPOSA-2 IMPRESS in the “Meiji Modernization” of Post-3G EGFR TKI Progression?

Nagasaka¹,

Ou²

2022

LCTT

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Tyrosine kinase inhibitors (TKIs) have become the preferred first line therapy for those patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Given superior progression free survival (PFS) and overall survival (OS) when compared to earlier generations, third generation EGFR TKIs have become the first choice therapy in many parts of the world. Even though multiple strategies are in development to target both “on-target” and “off-target” resistance, the continuation of EGFR TKIs at the time of progression remains a controversial topic. This commentary focuses on both the ”classic” clinical trials of IMpower150 and IMPRESS and compares them to the recently reported ORIENT-31 and ongoing MARIPOSA-2 to discuss the future therapeutic strategies in the setting of progression post-third generation EGFR TKIs.

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IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain

Cited by 166 publications

References 46 publications

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Progress, Challenges, and Prospects

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Progress, Challenges, and Prospects

Navigate Towards the Immunotherapy Era: Value of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Brain Metastases

ORIENT-31 as the Sakigake “Charging Samurai” Born of IMpower150 but Will MARIPOSA-2 IMPRESS in the “Meiji Modernization” of Post-3G EGFR TKI Progression?

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