FDA Approves Atezolizumab for Alveolar Soft Part Sarcoma

FDA

The FDA has approved atezolizumab (Tecentriq) for adult and pediatric patients aged 2 years and older with unresectable or metastatic alveolar soft part sarcoma (ASPS).

The safety and efficacy of the agent was examined in the open-label, single-arm study, referred to as Study ML39345 (NCT03141684). To be eligible for enrollment, patients were required to have histologically or cytologically confirmed ASPS that was not curable by surgery, and an ECOG performance status of up to 2.

If patients had known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, known clinically significant liver disease, or a history of idiopathic pulmonary fibrosis, they were excluded. Other exclusion criteria also included having pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan.

Adult and pediatric patients enrolled to trial were given 1200 mg or 15 mg/kg, respectively, of atezolizumab intravenously once every 21 days until progressive disease or intolerable toxicity.

Independent review committee–assessed overall response rate (ORR) and duration of response (DOR) by RECIST v1.1 criteria served as the main efficacy outcome measures of the trial.

Among the 49 patients enrolled, the median age was 31 years (range, 12-70); 2% (n = 47) of patients were at least 65 years of age, and the 2 pediatric patients were at least 12 years of age. Moreover, 51% of patients were female and 55% were White. Regarding ECOG performance status, 53% had a status of 0 and 45% had a status of 1.

All patients previously underwent surgery for their disease and more than half (55%) received at least 1 previous line of therapy. Fifty-five percent of patients received prior radiotherapy and 53% had prior chemotherapy. All patients who reported their disease stage at the time of their initial diagnosis had stage IV disease.

Data showed that atezolizumab elicited an ORR of 24% (95% CI, 13%-39%), which included a partial response rate of 24%. The median DOR was not evaluable (NE; 95% CI, 17.0-NE), with 67% of patients experiencing a response that persisted for at least 6 months and 42% experiencing a response that lasted for 12 months or longer.

The safety of atezolizumab was examined in a total of 47 adult patients and 2 pediatric patients. The median duration of exposure to the drug was 8.9 months (range, 1-40).

The most common adverse reactions to occur in 15% or more of patients were musculoskeletal pain (67%), fatigue (55%), rash (47%), cough (45%), nausea (43%), headache (43%), hypertension (43%), vomiting (37%), constipation (33%), dyspnea (33%), dizziness (29%), hemorrhage (29%), insomnia (27%), diarrhea (27%), pyrexia (25%), anxiety (25%), abdominal pain (25%), hypothyroidism (25%), decreased appetite (22%), arrhythmia (22%), influenza-like illness (18%), decreased weight (18%), allergic rhinitis (16%), and increased weight (16%).

Forty-one percent of patients experienced serious adverse reactions to the treatment, and 35% required dose interruptions due to toxicity.

The recommended dosage of the agent for adult patients is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks until progressive disease or intolerable toxicity. For pediatric patients ag ed 2 years and older, the recommended dosage is 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

References

1. FDA grants approval to atezolizumab for alveolar soft part sarcoma. News release. FDA. December 9, 2022. Accessed December 9, 2022. https://bit.ly/3uC2hGe
2. Atezolizumab (Tecentriq). Prescribing information. Genentech, Inc.; 2022. Accessed December 9, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761034s047lbl.pdf