Checkpoint Inhibitor Nabs FDA Approval for Alveolar Soft Part Sarcoma

The FDA has approved atezolizumab (Tecentriq) for the treatment of alveolar soft part sarcoma (ASPS), the agency announced on Friday.

Atezolizumab, a PD-L1 immune checkpoint inhibitor already approved in lung cancers and other tumor types, is now also indicated for unresectable or metastatic ASPS in adult and pediatric patients ages 2 years and up.

ASPS is one of the rarest types of sarcoma, with only about 80 cases diagnosed each year in the U.S., according to the National Cancer Institute. The soft-tissue sarcoma typically starts as a painless lump in the muscles, fat, or nerves of the leg, and has often already metastasized before it is detected.

Approval was based on findings from Study ML39345, a single-arm trial involving 49 patients with ASPS that was incurable by surgery. Most were adults (median age 31 years) but the trial also included two children ages 12 and older.

The open-label study demonstrated an overall response rate of 24% (95% CI 13-39). Among the 12 responders, two-thirds had a response lasting 6 months or longer, while 42% had responses lasting a year or beyond.

Patients in the study were required to have an Eastern Cooperative Oncology Group performance status of 0-2, and were excluded if they had symptomatic central nervous system (CNS) metastases or a primary CNS malignancy, clinically significant liver disease, or a history of certain lung conditions such as idiopathic pulmonary fibrosis or pneumonitis, among others.

Common adverse events (those occurring in 15% or more of patients) included musculoskeletal pain, fatigue, headache, dizziness, rash, cough and dyspnea, nausea and vomiting, constipation or diarrhea, hypertension, hemorrhage, insomnia, anxiety, abdominal pain, hypothyroidism, arrhythmia, pyrexia or flu-like illness, allergic rhinitis, decreased appetite, and weight changes.

Grade 3/4 adverse events (occurring in 2% or more) in Study ML39345 included musculoskeletal pain (8%), hypertension and weight increases (6% each), headache and dizziness (4% each), along with fatigue, pyrexia, diarrhea, decreased appetite, rash, hemorrhage, and arrhythmia (all in 2% each), according to the drug’s updated label.

In adults, the recommended dosages include 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks until disease progression or unacceptable toxicity. In children ages 2 years and older, the recommended dosage is 15 mg/kg (1,200 mg maximum) given every 3 weeks.