Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with
Youngjoo Lee1, Ki Hyeong Lee2, Geon Kook Lee1
1Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
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.
Insights
Adding simvastatin to afatinib did not improve clinical benefit for nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC) patients. Both treatment arms showed similar response rates and survival outcomes in this phase II trial.
Area of Science:
- Oncology
- Clinical Pharmacology
- Lung Cancer Research
Background:
- Nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC) represents a distinct subtype requiring specific therapeutic strategies.
- Afatinib is a tyrosine kinase inhibitor used in NSCLC treatment.
- The potential role of statins in combination cancer therapy is an area of ongoing investigation.
Purpose of the Study:
- To evaluate the efficacy of combining simvastatin with afatinib versus afatinib monotherapy in previously treated NA-NSCLC patients.
- To determine if simvastatin addition offers a clinical benefit in this patient population.
- To assess response rate (RR), progression-free survival (PFS), and overall survival (OS) as primary and secondary endpoints.
Main Methods:
- A phase II, randomized study involving 68 advanced NA-NSCLC patients who progressed after chemotherapy.
- Patients were assigned to either simvastatin plus afatinib (AS arm) or afatinib alone (A arm).
- Primary endpoint was response rate (RR); PFS and OS were also analyzed.
Main Results:
- No significant difference in RR between the AS (5.7%) and A (9.4%) arms (p=0.440).
- Median PFS was 1.0 month for AS vs. 3.6 months for A (p=0.240); median OS was 10.0 months for AS vs. 7.0 months for A (p=0.930).
- Skin rash severity was inversely correlated with progression risk for afatinib (HR=0.44, p=0.005).
Conclusions:
- The addition of simvastatin to afatinib did not demonstrate a significant improvement in efficacy for NA-NSCLC patients.
- No significant differences in RR, PFS, or OS were observed between the combination and monotherapy arms.
- Further research may explore the predictive role of skin rash in afatinib treatment response.
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