A study published by Naing et al in the Journal for ImmunoTherapy of Cancer found that treatment with pembrolizumab demonstrated acceptable toxicity and antitumor activity in patients with four types of advanced, hard-to-treat rare cancers.

“Our findings that pembrolizumab has a favorable toxicity profile and [showed] antitumor activity in patients with these rare cancers supports further evaluation in these populations,” said first study author Aung Naing, MD, Associate Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. “Finding solutions for treatment is vital, given that patients with advanced rare cancers have a poor prognosis and few treatment options.”

Rare cancers are defined by the American Cancer Society as those with an incidence of fewer than six cases per 100,000 people per year.

Study Methods and Types of Rare Cancers

The open-label phase II study included 127 patients who had advanced rare cancers: cutaneous squamous cell carcinoma, carcinoma of unknown primary, adrenocortical carcinoma, and paraganglioma-pheochromocytoma.

Patients received 200 mg of pembrolizumab every 3 weeks between August 2016 and July 2018. All patients had tumors that had progressed on standard therapies. The primary endpoint of the study was nonprogression rate at 27 weeks on treatment; secondary endpoints were safety and tolerability, objective response rate, and clinical benefit rate.

Results

At data cutoff, the median nonprogression rate was 28% for the 127 patients with advanced rare cancers. Complete response, partial response, or stable disease after 4 months were observed in 38% of the patients. Nonprogression rates for each cancer group were: 36% for cutaneous squamous cell carcinoma, 33% for carcinoma of unknown primary, 31% for adrenocortical carcinoma, and 43% for paraganglioma-pheochromocytoma.

Treatment-related adverse events occurred in 52% of patients, with the most common side effects being fatigue and rash. Six deaths that were unrelated to treatment were reported.

“Studies such as this one are key, since rare cancers collectively accounted for 13% of all new cancer diagnoses and 25% of all cancer-related deaths in adults in 2017,” said Dr. Naing. “The 5-year survival rate is 15% to 20% lower than for more common cancers. The poor outcomes associated with rare cancers have been attributed to difficulty or delay in diagnosis, limited access to centers with expertise [in treating these cancers], and limited therapeutic options.”

The study authors concluded, “The favorable toxicity profile and antitumor activity seen in patients with squamous cell carcinoma of [the] skin, adrenocortical carcinoma, carcinoma of unknown primary, and paraganglioma-pheochromocytoma supports further evaluation of pembrolizumab in this patient population.”

Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.