Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials.
BACKGROUND
mTOR inhibitors are currently used in the treatment of solid malignancies. Since their approval, several cases of pulmonary toxicity (PT) have been described. This analysis aims to report the incidence and the risk of PT in published randomized controlled trials.


METHODS
PubMed and Scopus were reviewed for phase II-III randomized controlled trials with temsirolimus and everolimus. The characteristic of each study and incidence of all- and high-grades PT were collected.


RESULTS
A total of 2233 patients were available for meta-analysis: 989 had breast cancer, 833 had neuroendocrine tumor and 411 had metastatic renal cell carcinoma. In patients taking mTOR inhibitors, the incidence of all- and high-grades PT was 10.4% and 2.4%, respectively. Compared to controls, the relative risk for all- and high-grades PT was 31- and 8.8-folds, respectively. No significant heterogeneity was observed between the studies. Not any relationship was found between the incidence of lung metastases, treatment exposure and the incidence of PT.


CONCLUSIONS
The high grade PT is a rare event and 10% of patients may experience mild grade toxicity with a worsening of quality of life and interruption of therapy in some cases. We recommend monitoring of PT in patients treated with mTOR inhibitors.
Dipartimento di Scienze Radiologiche, Oncologiche e Anatomo-Patologiche, Sapienza Università di Roma, Rome, Italy. roberto.iacovelli@alice.it
Roberto
R
Iacovelli
Antonella
A
Palazzo
Silvia
S
Mezi
Federica
F
Morano
Giuseppe
G
Naso
Enrico
E
Cortesi
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000068338:Everolimus; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000188:drug therapy; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D009369:Neoplasms / Q000188:drug therapy*; D018358:Neuroendocrine Tumors / Q000188:drug therapy; D011014:Pneumonia / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic; D012129:Respiratory Function Tests; D012306:Risk; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus