Phase II study of everolimus (RAD001) in previously treated small cell lung cancer

Ahmad Tarhini, Athanasios Kotsakis, William Gooding, Yongli Shuai, Daniel Petro, David Friedland, Chandra Belani, Sanja Dacic, Athanassios Argiris

Research output: Contribution to journalArticle

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Abstract

Purpose: Mammalian target of rapamycin (mTOR) is a promising target in small cell lung cancer (SCLC). We designed a phase II study of everolimus, an mTOR inhibitor, in previously treated, relapsed SCLC. Experimental Design: Patients were treated with everolimus 10 mg orally daily until disease progression. The primary endpoint was disease control rate (DCR) at 6 weeks. PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue. Results: A total of 40 patients were treated: 23 had 1 prior regimen/sensitive relapse, 4 had 1 prior regimen/refractory, and 13 had 2 prior regimens. Twenty-eight patients received 2 or more cycles of everolimus, 7 received 1 cycle, and 5 did not complete the first cycle. Best response in 35 evaluable patients: 1 (3%) partial response (in sensitive relapse), 8 (23%) stable disease, and 26 (74%) progression; DCR at 6 weeks was 26% (95% CI = 11-40). Median survival was 6.7 months and median time to progression was 1.3 months. Grade 3 toxicities included thrombocytopenia (n = 2), neutropenia (n = 2), infection (n = 2), pneumonitis (n = 1), fatigue (n = 1), elevated transaminases (n = 1), diarrhea (n = 2), and acute renal failure (n = 1). High phosphorylated AKT expression was modestly associated with overall survival (HR = 2.07; 95% CI = 0.97-4.43). Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression (P = 0.0093). Conclusions: Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC. Further evaluation in combination regimens for patients with sensitive relapse may be considered.

Original languageEnglish (US)
Pages (from-to)5900-5907
Number of pages8
JournalClinical Cancer Research
Volume16
Issue number23
DOIs
StatePublished - Dec 1 2010

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Small Cell Lung Carcinoma
Sirolimus
Recurrence
Ribosomal Protein S6 Kinases
Survival
Everolimus
Transaminases
Neutropenia
Phosphatidylinositol 3-Kinases
Acute Kidney Injury
Antineoplastic Agents
Fatigue
Disease Progression
Diarrhea
Pneumonia
Research Design
Biomarkers
Infection

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tarhini, A., Kotsakis, A., Gooding, W., Shuai, Y., Petro, D., Friedland, D., ... Argiris, A. (2010). Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. Clinical Cancer Research, 16(23), 5900-5907. https://doi.org/10.1158/1078-0432.CCR-10-0802
Tarhini, Ahmad ; Kotsakis, Athanasios ; Gooding, William ; Shuai, Yongli ; Petro, Daniel ; Friedland, David ; Belani, Chandra ; Dacic, Sanja ; Argiris, Athanassios. / Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 23. pp. 5900-5907.
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Tarhini, A, Kotsakis, A, Gooding, W, Shuai, Y, Petro, D, Friedland, D, Belani, C, Dacic, S & Argiris, A 2010, 'Phase II study of everolimus (RAD001) in previously treated small cell lung cancer', Clinical Cancer Research, vol. 16, no. 23, pp. 5900-5907. https://doi.org/10.1158/1078-0432.CCR-10-0802

Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. / Tarhini, Ahmad; Kotsakis, Athanasios; Gooding, William; Shuai, Yongli; Petro, Daniel; Friedland, David; Belani, Chandra; Dacic, Sanja; Argiris, Athanassios.

In: Clinical Cancer Research, Vol. 16, No. 23, 01.12.2010, p. 5900-5907.

Research output: Contribution to journalArticle

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T1 - Phase II study of everolimus (RAD001) in previously treated small cell lung cancer

AU - Tarhini, Ahmad

AU - Kotsakis, Athanasios

AU - Gooding, William

AU - Shuai, Yongli

AU - Petro, Daniel

AU - Friedland, David

AU - Belani, Chandra

AU - Dacic, Sanja

AU - Argiris, Athanassios

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Y1 - 2010/12/1

N2 - Purpose: Mammalian target of rapamycin (mTOR) is a promising target in small cell lung cancer (SCLC). We designed a phase II study of everolimus, an mTOR inhibitor, in previously treated, relapsed SCLC. Experimental Design: Patients were treated with everolimus 10 mg orally daily until disease progression. The primary endpoint was disease control rate (DCR) at 6 weeks. PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue. Results: A total of 40 patients were treated: 23 had 1 prior regimen/sensitive relapse, 4 had 1 prior regimen/refractory, and 13 had 2 prior regimens. Twenty-eight patients received 2 or more cycles of everolimus, 7 received 1 cycle, and 5 did not complete the first cycle. Best response in 35 evaluable patients: 1 (3%) partial response (in sensitive relapse), 8 (23%) stable disease, and 26 (74%) progression; DCR at 6 weeks was 26% (95% CI = 11-40). Median survival was 6.7 months and median time to progression was 1.3 months. Grade 3 toxicities included thrombocytopenia (n = 2), neutropenia (n = 2), infection (n = 2), pneumonitis (n = 1), fatigue (n = 1), elevated transaminases (n = 1), diarrhea (n = 2), and acute renal failure (n = 1). High phosphorylated AKT expression was modestly associated with overall survival (HR = 2.07; 95% CI = 0.97-4.43). Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression (P = 0.0093). Conclusions: Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC. Further evaluation in combination regimens for patients with sensitive relapse may be considered.

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Tarhini A, Kotsakis A, Gooding W, Shuai Y, Petro D, Friedland D et al. Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. Clinical Cancer Research. 2010 Dec 1;16(23):5900-5907. https://doi.org/10.1158/1078-0432.CCR-10-0802