NEW YORK (Reuters Health) – Drug-related pneumonitis is a class-effect toxicity of mammalian target of rapamycin (mTOR) inhibitors and temsirolimus is no exception, new research confirms.

In the Global Advanced Renal Cell Carcinoma (ARCC) trial, pneumonitis occurred in close to 30% of patients on the drug, Dr. Jose Pablo Maroto, of Sant Pau Hospital, Barcelona, Spain and colleagues reported March 28 in the Journal of Clinical Oncology.

“Patients with ARCC receiving temsirolimus should be monitored closely for development of pneumonitis, and their management should be altered if clinical symptoms appear,” the study team concludes.

RCC is the most common and lethal type of kidney cancer in adults. When surgery is not possible due to metastatic disease, targeted therapy with temsirolimus has yielded improved survival rates over interferon therapy. However, pneumonitis related to the drug has been reported in 2% to 36% of patients receiving it.

Dr. Maroto’s team designed their study to more accurately gauge the incidence of temsirolimus-related pneumonitis and identify radiographic patterns in patients with ARCC.

They reviewed sequential chest computed tomography images obtained from 208 patients who received intravenous temsirolimus 25 milligrams once weekly and 200 who received subcutaneous interferon alfa 3 million units, with an increase to 18 million units, twice weekly. All were part of the global ARCC trial.

According to the investigators, changes on CT consistent with pneumonitis were seen in 8 of 138 evaluable patients treated with interferon compared with 52 of 178 evaluable patients treated with temsirolimus (6% vs 29%). “This incidence is similar to that reported for other retrospective, independent radiographic analyses of patients treated with mTOR inhibitors, the researchers say.

Ground glass opacities and consolidation, either alone or in combination and often involving multiple lobes, were the most commonly observed abnormalities.

The onset of drug-related pneumonitis occurred within the first 8 weeks of temsirolimus treatment in 60% of patients (31 of 52). The estimated cumulative probability of pneumonitis 8 weeks after the first dose of temsirolimus was 21% and increased to 31% at 16 weeks and 45% at 13 months. The corresponding figures for interferon were 6%, 8% and 16%.

Sixteen of the 52 patients (31%) who developed pneumonitis while taking temsirolimus had respiratory symptoms around the time that signs of pneumonitis were seen on CT, the researchers say. Increased cough and dyspnea were the most common symptoms.

This study, the researchers conclude, provides more evidence that radiographically-detected pneumonitis is a common adverse effect of mTOR inhibitors in patients with cancer. They recommend that clinicians “review chest CT images for radiographic signs of pneumonitis as part of close monitoring during treatment.”

They further advise that patients with radiographic changes indicative of pneumonitis who have no clinical symptoms continue treatment with an mTOR inhibitor but be closely monitored for respiratory symptoms.

They say patients receiving mTOR inhibitor therapy who develop respiratory symptoms concurrent with radiographic changes, on the other hand, should stop treatment pending further evaluation and management, which may include pulmonary function tests and bronchoscopy as well as initiation of empiric treatments such as corticosteroids and antibiotics.

mTOR inhibitor therapy might be resumed, with or without dose adjustment, depending on the patient’s clinical course and response to empiric therapies, availability of alternative therapies and overall risk/benefit assessment, the clinicians conclude.

J Clin Oncol