Treatment of desmoid tumors

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28]

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28]

The median PFS could not be estimated in the nirogacestat group (due to a low number of events) and was 15.1 months in the placebo group. The risk of disease progression or death was 71% lower in the nirogacestat group (HR, 0.29; 95% CI, 0.15–0.55; P < .001).[28][Level of evidence B1]

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28]

The objective response rate was 41% in the nirogacestat group and 8% in the placebo group (P < .001). Complete responses occurred in 7% of patients in the nirogacestat group and 0% of patients in the placebo group.

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28]

Several patient-reported outcome measures were collected and assessed, including: Compared with patients in the placebo group, patients in the nirogacestat group had significantly improved scores across all assessments (P < .001).

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28] › Several patient-reported outcome measures were collected and assessed, including: Compared with patients in the placebo group, patients in the nirogacestat group had significantly improved scores across all assessments (P < .001).

Brief Pain Inventory-Short Form.

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28] › Several patient-reported outcome measures were collected and assessed, including: Compared with patients in the placebo group, patients in the nirogacestat group had significantly improved scores across all assessments (P < .001).

GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS) (comprising the Desmoid Tumor Impact Scale physical functioning domain score and the Desmoid Tumor Symptom Scale).

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28] › Several patient-reported outcome measures were collected and assessed, including: Compared with patients in the placebo group, patients in the nirogacestat group had significantly improved scores across all assessments (P < .001).

European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scales for global health status-quality of life, physical functioning, and role functioning.

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28]

Most (95%) adverse events were grade 1 or 2. The most common events (i.e., affecting >20% of patients) were diarrhea, nausea, fatigue, hypophosphatemia, maculopapular rash, stomatitis, headache, dermatitis acneiform, and vomiting.

A phase III placebo-controlled trial (NCT03785964) included adults with progressing desmoid tumors who had either not received prior therapy or whose disease was refractory to prior therapy. Patients were stratified according to tumor location (intra-abdominal vs. extra-abdominal). Patients were randomly assigned to receive either oral nirogacestat (150 mg twice daily) or placebo (twice daily). A total of 142 patients were assigned (70 to the nirogacestat group and 72 to the placebo group) across 37 sites in the United States, Canada, and Europe. Thirty-seven patients in each group were women of childbearing potential. A total of 110 patients (77%) had previously undergone systemic therapy, radiation therapy, or surgery. The median follow-up was 15.9 months.[28]

Ovarian dysfunction (defined as amenorrhea, premature menopause, menopause, and ovarian failure) occurred in 27 of 36 women (75%) of childbearing potential. Of these 27 women, 20 (74%) had resolution of their adverse event, 5 (19%) had unresolved ovarian dysfunction, and 2 (7%) had an unknown resolution status.