Reply to “mTOR inhibitor-related pulmonary toxicity; incidence even higher”

To the Editor,

We read the letter published by Willemsen and van Herpen [1] concerning the uncorrected incidence of pulmonary toxicity (PT) reported in our previous article [2].

The suggested correction was to increase the incidence of all grade toxicity from 10.4% to 12.1% (95% CI 10.3–13.9), and for high grade toxicity from 2.4% to 2.8% (95% CI 1.9–3.8). Based on this data we recalculated the relative risks (RR): when all grades of PT were considered, the RR was 37.7 (95% CI 10.7–132.3; p < 0.001) and no heterogeneity was found (Q = 1.3, p = 0.86; I² = 0%) (Figure 1a). When high grade PT were considered, the RR was 10.5 (95% CI 2.9–37.8; p < 0.001) and no heterogeneity was found (Q = 0.1, p = 0.99; I² = 0%) (Figure 1b).

Figure 1. Relative risk for all grades (a) or high grade (b) pulmonary toxicity in patients treated with mTOR inhibitors compared to controls.

We performed a sensitivity analysis to test the effect of control on RR and we found greater RR in trials comparing mTORi with the placebo (RR: 51.6; 95% CI 7.2–369.1; p < 0.001) compared to trials using active controls (RR: 30.4; 95% CI 5.9–155.2; p < 0.001) for all grades of PT. However, considering the overlap of confidence intervals these differences cannot be considered significant. Similarly, differences were not found for high grade PT in placebo versus active controls (RR: 10.7 vs. 10.3, respectively).

These data confirmed our conclusion and those reported by Willemsen and van Herpen that patients treated with mTOR inhibitors have an increased risk of PT and that these patients require an accurate monitoring of PT in order to improve their quality of life, treatment compliance and finally its effectiveness.

Declaration of interest: The authors report no declaration of interest. The authors alone are responsible for the content and writing of the paper.