CheckMate 012: Safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC.

Hellmann, Matthew D.; Gettinger, Scott; Goldman, Jonathan W.; Brahmer, Julie R.; Borghaei, Hossein; Chow, Laura Q.; Ready, Neal; Gerber, David E.; Juergens, Rosalyn A.; Shepherd, Frances A.; Laurie, Scott A.; Zhou, Ye; Geese, William J.; Agrawal, Shruti; Li, Xuemei; Antonia, Scott

doi:10.1200/jco.2016.34.15_suppl.3001

Cited by 61 publications

(47 citation statements)

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“…This hypothesis has now been validated in various clinical trials. 18,31,39 Several limitations of our study need to be mentioned. This analysis focused on predictive criteria of response to PD-1-PD-L1 blockade based on in situ multiparametric immunofluorescence analysis.…”

Section: Cd8mentioning

confidence: 95%

Composite biomarkers defined by multiparametric immunofluorescence analysis identify ALK-positive adenocarcinoma as a potential target for immunotherapy

et al. 2017

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Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. CD8C T cells was also observed in ALK-positive lung cancer patients compared with EGFR-mutated (p D 0.03) or WT patients (p D 0.012). These results strongly suggest that a subgroup of ALK-positive lung cancer patients may constitute good candidates for anti-PD-1/-PD-L1 therapies.

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Section: Cd8mentioning

confidence: 95%

Composite biomarkers defined by multiparametric immunofluorescence analysis identify ALK-positive adenocarcinoma as a potential target for immunotherapy

et al. 2017

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“…A phase III study of osimertinib plus durvalumab has been prematurely closed because of the high rate of pulmonary toxicities observed with such combination (NCT 02454933). Finally preliminary results of the CheckMate 012 study have recently shown a partial response (PR) in 4/8 EGFR-mutated patients receiving nivolumab plus ipilimumab combination (Hellmann et al, 2016). As suggested by all these translational and clinical data, more efforts are needed in order to clarify the complex interaction between EGFR molecular pathway and anti-tumor immune response, and ultimately select those patients who may benefit from these combinations.…”

Section: Immunotherapymentioning

confidence: 99%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy

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“…In a recent presentation, response rates of 13 to 39% were reported, with median duration of response not reached yet (median follow-up 16.6 months). 120 CheckMate 227 is investigating nivolumab with or without ipilimumab, compared with standard platinum-doublet chemotherapy with or without nivolumab depending on the PD-L1 status in the first-line treatment of advanced or metastatic NSCLC. 121 In a phase I study, the combination of durvalumab and tremelimumab showed a manageable tolerability profile, with antitumour activity in patients with locally advanced or metastatic NSCLC, irrespective of PD-L1 status.…”

Section: Combined Immunotherapeutic Approachesmentioning

confidence: 99%

Immunotherapy and Targeted Therapies in the Treatment of Non-small Cell Lung Cancer

Nguyen-Ngoc¹,

Reck²,

Tan³

et al. 2017

European Oncology &Amp; Haematology

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In the last decade, the emergence of targeted therapies has changed the treatment paradigm for non-small cell lung cancer (NSCLC). The growing availability of therapies targeting specific genetic alterations, such as epidermal growth factor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, have led to changes in the guidelines to reflect the need for molecular profiling. More recently, immunotherapeutic approaches have been investigated in the treatment setting of NSCLC, and these may provide superior outcomes and have substantially better tolerability compared to chemotherapy. Immunotherapies currently available for NSCLC include the checkpoint inhibitors anti-PD-1 antibodies nivolumab and pembrolizumab. Several other anti-PD-L1 compounds such as atezolizumab, durvalumab and avelumab are also very advanced in clinical investigation, in monotherapy as well as in combination with immune priming phase activators anti-CTLA4 ipilimumab and tremelimumab, across all treatment lines. The challenge facing oncologists is identifying which therapy is best suited to the individual patient.

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CheckMate 012: Safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC.

Cited by 61 publications

References 0 publications

Composite biomarkers defined by multiparametric immunofluorescence analysis identify ALK-positive adenocarcinoma as a potential target for immunotherapy

Composite biomarkers defined by multiparametric immunofluorescence analysis identify ALK-positive adenocarcinoma as a potential target for immunotherapy

EGFR inhibition in NSCLC: New findings…. and opened questions?

Immunotherapy and Targeted Therapies in the Treatment of Non-small Cell Lung Cancer

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