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Published on: February 12, 2017
Phase II study of everolimus (RAD001) in previously treated small cell lung cancer
Ahmad Tarhini1, Athanasios Kotsakis, William Gooding
1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
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.
Insights
Everolimus showed limited effectiveness as a single treatment for relapsed small cell lung cancer (SCLC). Further research into combination therapies for sensitive relapse SCLC patients is recommended.
Area of Science:
- Oncology
- Pharmacology
Background:
- Mammalian target of rapamycin (mTOR) is a validated therapeutic target in various cancers.
- Small cell lung cancer (SCLC) remains a challenging malignancy with limited treatment options for relapsed disease.
Purpose of the Study:
- To evaluate the efficacy and safety of everolimus, an mTOR inhibitor, in patients with previously treated, relapsed SCLC.
- To assess the disease control rate (DCR) at 6 weeks as the primary endpoint.
Main Methods:
- A phase II study treated 40 patients with relapsed SCLC with oral everolimus (10 mg daily) until disease progression.
- Tumor tissue was analyzed for PI3K/Akt signaling pathway biomarkers.
- Disease control rate (DCR), overall survival, and progression-free survival were assessed.
Main Results:
- The DCR at 6 weeks was 26% (95% CI = 11-40), with 1 partial response and 8 cases of stable disease among 35 evaluable patients.
- Median overall survival was 6.7 months, and median time to progression was 1.3 months.
- High phosphorylated AKT expression showed a modest association with overall survival, while higher S6 kinase expression correlated with disease control.
Conclusions:
- Everolimus demonstrated limited single-agent antitumor activity in previously treated, relapsed SCLC patients.
- The drug was generally well-tolerated, with manageable toxicities.
- Combination regimens involving everolimus may warrant further investigation, particularly for patients with sensitive relapse SCLC.
