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

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

doi:10.1016/j.jtho.2018.05.002

Cited by 174 publications

(138 citation statements)

References 19 publications

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“…[22][23][24][25] Immunotherapy clinical studies have suggested that treatment with checkpoint inhibitors may be viable options for ES-SCLC patients. [26][27][28] The IMpower133 study-a double-blind, placebo-controlled, Phase 3 trial that evaluated atezolizumab plus carboplatin and etoposide in patients with ES-SCLC who had not previously received treatment (N = 202)-showed that the addition of atezolizumab extended OS (10.3 months to 12.3 months) improved the 1-year survival rate (38.2% to 51.7%), and increased the complete response rate (1.0% to 2.5%) compared to the placebo group (N = 202). Moreover, the survival benefit was most pronounced in patients older than 65 years, who had an Eastern Cooperative Oncology Group score of 1 and no brain or liver metastases.…”

Section: Discussionmentioning

confidence: 99%

<p>Thoracic Radiotherapy Benefits Elderly Extensive-Stage Small Cell Lung Cancer Patients with Distant Metastasis</p>

Sun

et al. 2019

CMAR

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Purpose: Thoracic radiotherapy (TRT) is the recommended therapeutic regimen for extensive-stage small cell lung cancer (ES-SCLC). Little is known about TRT benefits in elderly populations. The aim of this study was to evaluate TRT effects on the prognosis of elderly patients with ES-SCLC. Patients and methods: This retrospective analysis reviewed the records of patients over 65 years of age with metastatic ES-SCLC treated between 2010 and 2016. Enrolled patients received standard chemotherapy regimens (etoposide plus cisplatin or carboplatin). A total of 93 eligible patients were subjected to propensity score matching, which led to 40 patients being assigned to the TRT group and 40 to the no thoracic radiotherapy (noTRT) group. The cohort of 80 patients (67 males) had the median age of 69 years (range, 65-85 years), with a median of 4 chemotherapy cycle (range, 1-8 cycles), and a median chest irradiation dose of 50 Gy (range, 30-60 Gy). We analyzed overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) as endpoints; survival rates were determined by the Kaplan-Meier method and compared across groups with log-rank tests. Multivariate prognostic analysis was performed with Cox regression modeling, and categorical variables were analyzed with Chi-square tests. Results: In all patients, the 1-year OS, PFS, and LRFS rates were 38.3%, 16%, and 17.9%, respectively. The TRT group had superior survival outcomes compared to the noTRT group: their 1-year OS, PFS, and LRFS rates were 55% vs. 25% (P < 0.001), 32.1% vs. 0% (P < 0.001), and 31% vs. 2.6% (P < 0.001), respectively. TRT did not increase the incidence of adverse reactions (P = 0.431). Conclusion: TRT can improve chest tumor control and survival time in elderly ES-SCLC patients. Large-scale studies to further assess the benefits of TRT are warranted.

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Section: Discussionmentioning

confidence: 99%

<p>Thoracic Radiotherapy Benefits Elderly Extensive-Stage Small Cell Lung Cancer Patients with Distant Metastasis</p>

Sun

et al. 2019

CMAR

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“…Patients who did not have progression after completion of first-line chemotherapy were eligible for a single-arm study of maintenance pembrolizumab. 95 In 45 patients, pembrolizumab was well tolerated but the median PFS of only 1.4 months did not meet its primary endpoint. A larger, phase III maintenance study reported similar results.…”

Section: Relapsed/refractory Sclc: Immune-checkpoint Inhibition (Io)mentioning

confidence: 97%

Small Cell Lung Cancer: Advances in Diagnosis and Management

Chauhan

Liu

2020

Semin Respir Crit Care Med

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Small cell lung cancer (SCLC) is an aggressive subtype of lung cancer characterized by rapid growth and early spread. It is a highly lethal disease that typically is diagnosed at a late stage. Surgery plays a very small role in this cancer, and management typically involves chemotherapy, delivered with thoracic radiation in early-stage disease. Platinum-based chemotherapy is initially very effective, inducing rapid and often deep responses. These responses, though, are transient, and upon relapse, SCLC is highly refractory to therapy. Immunotherapy has shown promise in delivering meaningful, durable responses and the addition of immunotherapy to first-line chemotherapy has led to the first improvements in survival in decades. Still, the disease remains difficult to manage. Incorporating radiation therapy at specific points in patient management may improve disease control. The development of predictive biomarkers and novel targeted therapies will hopefully improve options for patients in the near future. This review focuses on the current standards of care and future directions.

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“…In other solid malignancies, only four studies reported efficacy and/or survival outcomes of patients with brain metastases, who were treated with ICI. First, in the phase II trial of Gadgeel et al, patients with small cell lung cancer (SCLC) were treated with pembrolizumab, 200 mg Q3W [54]. The median survival of these patients was 9.6 months (95% CI 7.0-12.0) and patients had a median PFS of 1.4 months (95% CI 1.2-2.8).…”

Section: Outcomes Of Immune Checkpoint Inhibitors In Brain Metastasesmentioning

confidence: 99%

The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review

Brahm

Linde

Enting

et al. 2020

Cancers

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The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (n = 8 in glioblastoma and n = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients.

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

Abstract: 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.

Cited by 174 publications

References 19 publications

<p>Thoracic Radiotherapy Benefits Elderly Extensive-Stage Small Cell Lung Cancer Patients with Distant Metastasis</p>

<p>Thoracic Radiotherapy Benefits Elderly Extensive-Stage Small Cell Lung Cancer Patients with Distant Metastasis</p>

Small Cell Lung Cancer: Advances in Diagnosis and Management

The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review

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