Abstract CT043: Outcomes among patients (pts) with metastatic nonsquamous NSCLC with liver metastases or brain metastases treated with pembrolizumab (pembro) plus pemetrexed-platinum: Results from the KEYNOTE-189 study

Garassino, Marina Chiara; Gadgeel, Shirish M.; Esteban, Emilio; Felip, Enriqueta; Speranza, Giovanna; Angelis, F. De; Dómine, Manuel; Clingan, Philip R.; Hochmair, Maximilian; Powell, Steven; Cheng, Susanna Y.; Bischoff, Helge; Peled, Nir; Grossi, Francesco; Jennens, Ross; Reck, Martin; Hui, Rutai; Garon, Edward B.; Boyer, Michael; Rubio-Viqueira, Belén; Novello, Silvia; Kurata, Takeshi; Gray, Jhanelle E.; Cardellino, Anna; Yang, Jing; Pietanza, M. Catherine; Rodríguez-Abreu, Delvys

doi:10.1158/1538-7445.sabcs18-ct043

Cited by 10 publications

(8 citation statements)

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“…To our knowledge, this is the first study to focus on the population of patients with brain metastases from lung cancer and examine the effects of immunotherapy. Other studies have demonstrated that patients with brain metastases from NSCLC can benefit from immunotherapy both as a single agent 5,19,20 and in combination with chemotherapy, 21 however these reports were based on subset analyses from larger trials and did not assess the specific characteristics of the CNS disease. Several expanded access programs and observational studies examining patients with NSCLC treated with singleagent PD-1 or PD-L1 inhibitors found that clinical outcomes (including efficacy and safety) were similar in patients with versus without brain metastases, highlighting that both PD-1 and PD-L1 inhibitors can be effective in patients with CNS disease.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

Goldberg

Schalper

Gettinger

et al. 2020

The Lancet Oncology

409

319

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Background: We performed a phase II trial of pembrolizumab in patients with NSCLC or melanoma with untreated brain metastases to determine the activity of PD-1 blockade in the CNS. Interim results were previously published, and we now report an updated analysis of the full NSCLC cohort. Methods: This was an open-label, single-institution, phase 2 study. Eligible patients were ≥ 18 years of age with advanced NSCLC with ≥1 brain metastasis 5-20mm not previously treated or progressing after prior radiation, no neurologic symptoms or corticosteroid requirement, and performance status <2. Patients were treated with pembrolizumab 10 mg/kg IV every 2 weeks. Cohort 1 was for patients with PD-L1 ≥1% and cohort 2 PD-L1 <1% or unevaluable. The primary endpoint was the proportion of patients achieving a brain metastasis response. All treated patients were analyzed for response and safety endpoints. This study is closed to accrual and is registered with Clinicaltrials.gov, number NCT02085070. Here we report the updated results of the NSCLC cohort. Findings: Between March 31, 2014 and May 21, 2018, 42 patients were treated. Median followup was 8.3 months (IQR 4.5 to 26.2 months). Eleven of 37 patients in cohort 1 had a brain metastasis response (29.7% [95% CI, 15•9-47•0%]). There were no responses in cohort 2. Grade 3-4 AEs related to treatment included 2 patients with pneumonitis, and 1 each with constitutional symptoms, colitis, adrenal insufficiency, hyperglycemia, and hypokalemia. Treatment-related serious adverse events occurred in 6 (14%) patients and included pneumonitis acute kidney injury, colitis, hypokalemia, and adrenal insufficiency. There were no treatment-related deaths. Interpretation: Pembrolizumab has activity in brain metastases from NSCLC with PD-L1 expression ≥1% and is safe in select patients with untreated brain metastases. Further investigation of immunotherapy in patients with CNS disease from NSCLC is warranted.

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Section: Discussionmentioning

confidence: 99%

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

Goldberg

Schalper

Gettinger

et al. 2020

The Lancet Oncology

409

319

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“…Most clinical trials do not include advanced NSCLC patients with driver mutations. IMpower150 was the only study to include this type of patient, showing a positive trend in OS probably due to the addition of bevacizumab to the combination strategy, as previously discussed [ 43 ]. However, this therapeutic strategy for patients with EGFR/ALK mutations should be further confirmed in prospective, randomized studies.…”

Section: Discussionmentioning

confidence: 85%

“…Indeed, although other atezolizumab trials previously reported outcomes in patients with liver metastases, data from IMpower130 [ 41 ] and IMpower132 [ 42 ] showed no survival benefit with atezolizumab plus chemotherapy, supporting the benefits of adding the antiangiogenic agent in the combination [ 23 ]. Despite the fact that the updated KEYNOTE-189 analysis showed a clinical benefit of pembrolizumab-containing regimens over chemotherapy alone in patients with liver metastases (median OS 12.6 vs. 6.6, OS HR 0.62, 12-month OS rate 51% vs. 3%) [ 43 ], this baseline characteristic, in contrast with the IMpower trials, was not a stratification factor in the study.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, while PD-L1 immunohistochemistry was read on both tumor cells and tumor-infiltrating cells in the atezolizumab studies (IMpower) [ 20 , 24 , 25 , 29 , 43 ], PD-L1 expression was only measured on tumor cells in the trials assessing pembrolizumab (KEYNOTE) and nivolumab (CheckMate-227), [ 17 , 21 , 22 , 28 ]. Second, six of the included trials only provided interim analysis of the OS [ 17 , 20 , 22 , 24 , 25 , 28 , 29 , 43 ], which may misrepresent overall efficacy. Finally, the subgroup analysis was limited by the available information (PFS subgroup analyses were not assessed in CheckMate-227), and consequently caution must be exercised when interpreting the results.…”

Section: Discussionmentioning

confidence: 99%

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PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis

García‐González

Ruíz-Bañobre

Afonso-Afonso

et al. 2020

JCM

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The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57–0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67–0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70–2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.

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“…Some participants specifically selected a first line ICI-chemotherapy combination, even in PD-L1 ⩾50% patients, to minimise the risk of symptomatic BM progression. Furthermore, the combination of ICI ( pembrolizumab) and pemetrexed-platinum was superior to platinum-doublet chemotherapy in an exploratory analysis of the KEYNOTE189 trial BM subgroup [14]. Although not evaluated in a randomised trial, bevacizumab added to carboplatin-paclitaxel was mentioned as an option, based on the single arm phase II BRAIN trial (N=67) results, with a 61% intracranial objective response rate and a median survival of 16.0 months [15].…”

Section: Selection Of Type Of Treatmentmentioning

confidence: 99%

Current challenges in the management of nonsmall cell lung cancer brain metastases

2020

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Abstract CT043: Outcomes among patients (pts) with metastatic nonsquamous NSCLC with liver metastases or brain metastases treated with pembrolizumab (pembro) plus pemetrexed-platinum: Results from the KEYNOTE-189 study

Cited by 10 publications

References 0 publications

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis

Current challenges in the management of nonsmall cell lung cancer brain metastases

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