Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC)

Shirish M. Gadgeel, Nathan A. Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P. Kalemkerian

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Abstract

Objective: The aim of this study was to assess the efficacy of maintenance pembrolizumab in patients with extensive-stage SCLC after treatment with platinum and etoposide. Methods: Patients with extensive-stage SCLC with a response or stable disease after induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg administered intravenously every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary end point of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary end point. Available tumor tissue was assessed for expression of programmed death ligand 1 (PD-L1) both in the tumor cells and in the surrounding stroma. Blood for circulating tumor cells was collected before the first, second, and third cycles of pembrolizumab. Results: Of the 45 patients enrolled, 56% were male and 22% had treated brain metastases. The median PFS was 1.4 months (95% confidence interval [CI]: 1.3–2.8), with a 1-year PFS of 13%. The median OS was 9.6 months (95% CI: 7.0–12), with a 1-year OS of 37%. Of the 30 tumors that could be assessed, three had PD-L1 expression (≥1%) in the tumor cells. A total of 20 tumors could be assessed for PD-L1 expression in the stroma. The median PFS in the eight patients with tumors positive for expression of PD-L1 at the stromal interface was 6.5 months (95% CI: 1.1–12.8) compared with 1.3 months (95% CI: 0.6–2.5) in 12 patients with tumors negative for this marker. No unexpected toxicities were observed. Conclusion: Maintenance pembrolizumab did not appear to improve median PFS compared with the historical data. However, the 1-year PFS rate of 13% and OS rate of 37% suggest that a subset of patients did benefit from pembrolizumab.

Original languageEnglish (US)
JournalJournal of Thoracic Oncology
DOIs
StateAccepted/In press - Jan 1 2018

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Small Cell Lung Carcinoma
Disease-Free Survival
Maintenance
Confidence Intervals
Ligands
Neoplasms
Survival
Survival Rate
Circulating Neoplastic Cells
Induction Chemotherapy
Etoposide
Tumor Biomarkers
Platinum
pembrolizumab
Neoplasm Metastasis
Drug Therapy
Brain

Keywords

  • Maintenance
  • Metastatic
  • Pembrolizumab
  • SCLC

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC). / Gadgeel, Shirish M.; Pennell, Nathan A.; Fidler, Mary Jo; Halmos, Balazs; Bonomi, Philip; Stevenson, James; Schneider, Bryan; Sukari, Ammar; Ventimiglia, Jaclyn; Chen, Wei; Galasso, Cathy; Wozniak, Antoinette; Boerner, Julie; Kalemkerian, Gregory P.

In: Journal of Thoracic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Gadgeel, SM, Pennell, NA, Fidler, MJ, Halmos, B, Bonomi, P, Stevenson, J, Schneider, B, Sukari, A, Ventimiglia, J, Chen, W, Galasso, C, Wozniak, A, Boerner, J & Kalemkerian, GP 2018, 'Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC)', Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2018.05.002
Gadgeel, Shirish M. ; Pennell, Nathan A. ; Fidler, Mary Jo ; Halmos, Balazs ; Bonomi, Philip ; Stevenson, James ; Schneider, Bryan ; Sukari, Ammar ; Ventimiglia, Jaclyn ; Chen, Wei ; Galasso, Cathy ; Wozniak, Antoinette ; Boerner, Julie ; Kalemkerian, Gregory P. / Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC). In: Journal of Thoracic Oncology. 2018.
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abstract = "Objective: The aim of this study was to assess the efficacy of maintenance pembrolizumab in patients with extensive-stage SCLC after treatment with platinum and etoposide. Methods: Patients with extensive-stage SCLC with a response or stable disease after induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg administered intravenously every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary end point of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary end point. Available tumor tissue was assessed for expression of programmed death ligand 1 (PD-L1) both in the tumor cells and in the surrounding stroma. Blood for circulating tumor cells was collected before the first, second, and third cycles of pembrolizumab. Results: Of the 45 patients enrolled, 56{\%} were male and 22{\%} had treated brain metastases. The median PFS was 1.4 months (95{\%} confidence interval [CI]: 1.3–2.8), with a 1-year PFS of 13{\%}. The median OS was 9.6 months (95{\%} CI: 7.0–12), with a 1-year OS of 37{\%}. Of the 30 tumors that could be assessed, three had PD-L1 expression (≥1{\%}) in the tumor cells. A total of 20 tumors could be assessed for PD-L1 expression in the stroma. The median PFS in the eight patients with tumors positive for expression of PD-L1 at the stromal interface was 6.5 months (95{\%} CI: 1.1–12.8) compared with 1.3 months (95{\%} CI: 0.6–2.5) in 12 patients with tumors negative for this marker. No unexpected toxicities were observed. Conclusion: Maintenance pembrolizumab did not appear to improve median PFS compared with the historical data. However, the 1-year PFS rate of 13{\%} and OS rate of 37{\%} suggest that a subset of patients did benefit from pembrolizumab.",
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AU - Gadgeel, Shirish M.

AU - Pennell, Nathan A.

AU - Fidler, Mary Jo

AU - Halmos, Balazs

AU - Bonomi, Philip

AU - Stevenson, James

AU - Schneider, Bryan

AU - Sukari, Ammar

AU - Ventimiglia, Jaclyn

AU - Chen, Wei

AU - Galasso, Cathy

AU - Wozniak, Antoinette

AU - Boerner, Julie

AU - Kalemkerian, Gregory P.

PY - 2018/1/1

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N2 - Objective: The aim of this study was to assess the efficacy of maintenance pembrolizumab in patients with extensive-stage SCLC after treatment with platinum and etoposide. Methods: Patients with extensive-stage SCLC with a response or stable disease after induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg administered intravenously every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary end point of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary end point. Available tumor tissue was assessed for expression of programmed death ligand 1 (PD-L1) both in the tumor cells and in the surrounding stroma. Blood for circulating tumor cells was collected before the first, second, and third cycles of pembrolizumab. Results: Of the 45 patients enrolled, 56% were male and 22% had treated brain metastases. The median PFS was 1.4 months (95% confidence interval [CI]: 1.3–2.8), with a 1-year PFS of 13%. The median OS was 9.6 months (95% CI: 7.0–12), with a 1-year OS of 37%. Of the 30 tumors that could be assessed, three had PD-L1 expression (≥1%) in the tumor cells. A total of 20 tumors could be assessed for PD-L1 expression in the stroma. The median PFS in the eight patients with tumors positive for expression of PD-L1 at the stromal interface was 6.5 months (95% CI: 1.1–12.8) compared with 1.3 months (95% CI: 0.6–2.5) in 12 patients with tumors negative for this marker. No unexpected toxicities were observed. Conclusion: Maintenance pembrolizumab did not appear to improve median PFS compared with the historical data. However, the 1-year PFS rate of 13% and OS rate of 37% suggest that a subset of patients did benefit from pembrolizumab.

AB - Objective: The aim of this study was to assess the efficacy of maintenance pembrolizumab in patients with extensive-stage SCLC after treatment with platinum and etoposide. Methods: Patients with extensive-stage SCLC with a response or stable disease after induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg administered intravenously every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary end point of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary end point. Available tumor tissue was assessed for expression of programmed death ligand 1 (PD-L1) both in the tumor cells and in the surrounding stroma. Blood for circulating tumor cells was collected before the first, second, and third cycles of pembrolizumab. Results: Of the 45 patients enrolled, 56% were male and 22% had treated brain metastases. The median PFS was 1.4 months (95% confidence interval [CI]: 1.3–2.8), with a 1-year PFS of 13%. The median OS was 9.6 months (95% CI: 7.0–12), with a 1-year OS of 37%. Of the 30 tumors that could be assessed, three had PD-L1 expression (≥1%) in the tumor cells. A total of 20 tumors could be assessed for PD-L1 expression in the stroma. The median PFS in the eight patients with tumors positive for expression of PD-L1 at the stromal interface was 6.5 months (95% CI: 1.1–12.8) compared with 1.3 months (95% CI: 0.6–2.5) in 12 patients with tumors negative for this marker. No unexpected toxicities were observed. Conclusion: Maintenance pembrolizumab did not appear to improve median PFS compared with the historical data. However, the 1-year PFS rate of 13% and OS rate of 37% suggest that a subset of patients did benefit from pembrolizumab.

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KW - Metastatic

KW - Pembrolizumab

KW - SCLC

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