Pembrolizumab (pembro) plus platinum-based chemotherapy (chemo) in NSCLC with brain metastases: Pooled analysis of KEYNOTE-021, 189, and 407

Powell, Steven; Rodríguez-Abreu, Delvys; Langer, Corey J.; Tafreshi, Ali; Paz-Ares, L.; Kopp, Hans Georg; Rodríguez-Cid, Jerónimo Rafael; Kowalski, Dariusz M.; Cheng, Ying; Kurata, Takeshi; Awad, Mark M.; Lin, Jianxin; Zhao, Bin; Pietanza, M. Catherine; Piperdi, Bilal; Garassino, M.C.

doi:10.1093/annonc/mdz260.005

Cited by 32 publications

(34 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain metastases are not confirmed as a negative prognostic factor because ICIs may cross the blood-brain barrier and induce disease response in selected patients [31]. Data from both retrospective series [36] and clinical trials showed good activity of ICIs as a single agent [37] or in combination with chemotherapy [38] in patients with brain metastases.…”

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

View full text Add to dashboard Cite

Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group. Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan–Meier and Cox hazard methods were used for survival analysis. Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001). Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs).

show abstract

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…All of these had been con ducted in the firstline setting and had tested pembrolizumab plus platinum based chemotherapy. Cohort C of the KEYNOTE21 study assessed two differ ent pembrolizumab doses [8], while Co hort G [9,10], KEYNOTE189 [11] and KEYNOTE407 [12] contained chemo therapyonly control arms. Patients in cluded in KEYNOTE407 had squamous histology, whereas all of the other trial participants had been diagnosed with nonsquamous NSCLC.…”

Section: … and Pembrolizumabchemotherapy Combinationmentioning

confidence: 99%

“…De Braud et al reported updated results from the integrated analysis of the ALKA372001, STARTRK1 and STAR TRK2 trials that focused on lung cancer patients [8]. Out of 63 individuals, 53 and 10 had ROS1positive and NTRK positive lung cancer, respectively.…”

Section: Entrectinib In Ntrk-positive Diseasementioning

confidence: 99%

“…In similar vein, Powell et al reported an exploratory pooled analysis of the KEY NOTE021, 189, and 407 trials that evalu ated the outcomes in NSCLC patients with and without stable brain metastases at baseline [8]. These studies had tested firstline pembrolizumab plus platinum based chemotherapy compared to chemotherapy [912].…”

Section: … and Pembrolizumab Plus Chemotherapymentioning

confidence: 99%

See 1 more Smart Citation

Report from the ESMO 2019 Congress, Barcelona, September 27th – October 1st 2019

2019

memo

View full text Add to dashboard Cite

S66 Checkpoint inhibition in non-small-cell lung cancer: expanding the range of options S69 EGFR-positive tumors: the issue of optimal therapy across several lines S73 Frontline combinations of EGFR-and angiogenesis-targeted agents S75 Exploring synergy between anti-angiogenic drugs and immunotherapy S76 Innovations in the setting of rare mutations: ALK, ROS1, NTRK, NRG1 S78 CNS disease does not preclude successful treatment S80 Interview: Even infrequent actionable drivers are important S81 Emerging survival benefits in the small-cell setting Supported by Boehringer Ingelheim in the form of an unrestricted grant

show abstract

“…Although ICI are widely being used across diverse tumor types, patients with untreated and/or symptomatic BM were either excluded from pivotal clinical trials or the percentage included was very low, with those patients enrolled being hyper-selected [17][18][19][20][21][22][23][24][25][26][27]. Therefore, there are still some concerns about the safety/efficacy ratio of ICI in patients with BM.…”

mentioning

confidence: 99%

Combination Treatments with Immunotherapy in Brain Metastases Patients

2020

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many advanced cancers. However, in most pivotal trials, patients with brain metastases (BM) were either excluded, or only selected patients were allowed. Therefore, there are still some concerns about the safety/efficacy ratio of ICI in patients with BM. In this special report we will provide an overview on the biological rationale for using ICI in the treatment of BM, the reported BM-related outcomes of clinical trials with a focus on ICI plus chemotherapy and ICI plus ICI combinations. Last, we will provide future challenges with this strategy, as well as directions for future research.

show abstract

Pembrolizumab (pembro) plus platinum-based chemotherapy (chemo) in NSCLC with brain metastases: Pooled analysis of KEYNOTE-021, 189, and 407

Cited by 32 publications

References 0 publications

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Report from the ESMO 2019 Congress, Barcelona, September 27th – October 1st 2019

Combination Treatments with Immunotherapy in Brain Metastases Patients

Contact Info

Product

Resources

About