Cancer Res Treat.  2017 Oct;49(4):1001-1011. 10.4143/crt.2016.546.

Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with Advanced Nonadenocarcinomatous Non-small Cell Lung Cancer

• Lee Y
• Lee KH
• Lee GK
• Lee SH
• Lim KY
• Joo J
• Go YJ
• Lee JS
• Han JY

• KMID: 2394819
• DOI: http://doi.org/10.4143/crt.2016.546

Abstract

PURPOSE
This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).
MATERIALS AND METHODS
Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).
RESULTS
Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005).
CONCLUSION
There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.

Keyword

EGFR tyrosine kinase inhibitor; EGFR mutation; Non-small-cell lung carcinoma; Squamous cell carcinoma; Statin

MeSH Terms

Arm
Carcinoma, Non-Small-Cell Lung*
Carcinoma, Squamous Cell
Diarrhea
Disease-Free Survival
Drug Therapy
Exanthema
Fluorescence
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Immunohistochemistry
In Situ Hybridization
Receptor, Epidermal Growth Factor
Simvastatin*
Stomatitis
Receptor, Epidermal Growth Factor
Simvastatin

Figure

• 

  Fig. 1. CONSORT diagram.

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  Fig. 2. Survival outcomes by treatment arm. (A) Progression-free survival (PFS). (B) Overall survival (OS). SIM, simvastatin.

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  Fig. 3. Sixteen-week progression-free survival (PFS) rate by treatment arm, adverse effects, and epidermal growth factor receptor (EGFR) biomarkers. AS, simvastatin plus afatinib; A, afatinib; WT, wild type; MT, mutant; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry.

Reference

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