Desmoid Tumor Drug Shows Promise

Author: European Society for Medical Oncology
Published: 2022/09/11 - Updated: 2023/09/21
Publication Type: Clinical Trial - Peer-Reviewed: Yes
Contents: Summary - Definition - Introduction - Main - Related

Synopsis: Significant improvement in progression-free survival and response rate combined with reduced symptoms and better quality of life outcome of new treatment approach for patients with desmoid tumors. The gamma secretase inhibitor nirogacestat, which targets Notch, increases progression free survival and reduces symptoms in patients with desmoid tumors. Designing rigorous randomized controlled phase 3 trials in rare cancers is fundamental to improving patients' outcomes and quality of life.


Significant improvement in progression-free survival and response rate combined with reduced symptoms and better quality of life is reported as outcomes of a new treatment approach for patients with desmoid tumors, which are benign, but locally aggressive and invasive soft tissue tumors. By targeting the Notch pathway with the novel gamma-secretase inhibitor nirogacestat, researchers from the DeFi trial have obtained positive results for the first time with this approach. The results are reported at the ESMO Congress 2022. (1)

Main Digest

Desmoid tumors are rare, with an incidence of 3-5 cases per million people worldwide each year (2,3). Patients have an unpredictable disease course, and although not generally fatal, soft tissue tumors can cause symptoms that greatly impair quality of life.

"Due to local and aggressive growth, desmoid tumors can cause pain, disfigurement, and functional problems that can be a real burden for patients," said lead author Bernd Kasper, Mannheim Cancer Center, Germany.

The DeFi study included 142 patients with progressive desmoid tumors recruited from 37 centers worldwide.

"This is the largest and most rigorous randomized controlled study ever carried out in this tumor type," reported Kasper. "Results showed a statistically significant improvement in progression-free survival in patients randomized to nirogacestat compared to the placebo group, with a 71% lower risk of disease progression on average."

The response rate was also much higher - 41% in the nirogacestat arm and only 8% in the placebo arm; nearly one in ten patients (7%) showed a complete response with the agent.

The study measured patient-reported outcomes because of the major impact of desmoid tumors on quality of life.

"We saw a statistically significant benefit in reduction of pain and symptom burden and improvement in physical and role functioning and in health-related quality of life, which was impressive," noted Kasper. "We try to optimize local tumor control and reduce the symptom burden. But we have previously had no approved therapy for desmoid tumors. This study has the potential to lead to the first registration of a drug to treat patients with this disease."

"This is a unique study, critical in many aspects," said Jean-Yves Blay, Cancer Center of Lyon, France, who was not involved in the study. "The results show benefit for the first time with a novel treatment with a new mode of action in patients where treatment options are currently limited."

The Notch signaling pathway is implicated in the development and progression of many tumor types.

"The findings are practice-changing," added Blay. He predicted: "We will use nirogacestat as part of the treatment armamentarium for patients with desmoid tumors. But we will have to figure out how best to use it."

Remaining questions include which patients should be offered this treatment, where it fits current approaches, how to identify responders and the optimal duration of treatment. DeFi included patients with progressing tumors, but Blay and Kasper said that nirogacestat could also be considered in patients with pain and impaired functioning.

"This was a very smart study: it demonstrated the feasibility of carrying out a large, placebo-controlled trial - which is the highest quality clinical study to investigate the activity of an agent - in rare cancer by recruiting patients from a multinational group of reference centers and it demonstrated the importance of targeting the right patients with the right drug when designing clinical trials," Blay added.

"The trial included patients with volumetrically progressive disease, which provided a measurable way to select patients in need of treatment." He added: "The success of this study puts even more emphasis on having patients with rare cancers referred into reference centers, where clinical studies can be accomplished in record times with the potential to deliver new treatments to patients with orphan diseases."

The number of cancer patients referred to reference centers is increasing but could still be better in some regions, improving the outlook for patients with rare cancers. (4)


DT are rare, locally aggressive soft-tissue tumors without approved systemic therapy. Nirogacestat (Niro), a novel oral gamma-secretase inhibitor (GSI), has shown antitumor activity in patients with DT.


DeFi is a global, Phase 3, randomized, double-blind, placebo (PBO)-controlled trial in adults with progressing DT per RECIST v1.1 (NCT03785964). 142 participants were stratified by target tumor location (intra-/extra-abdominal) and randomized 1:1 to Niro (n=70) 150 mg or PBO (n=72) BID. The primary endpoint was progression-free survival (PFS) per blinded independent central review. Prespecified secondary endpoints were safety, objective response rate (ORR), and patient-reported outcomes (PROs).


Niro demonstrated significant PFS improvement compared with PBO (hazard ratio [HR], 0.29 [95% CI, 0.15, 0.55; P<0.001]). ORR was significantly improved with Niro versus PBO (41% vs. 8%; P<0.001), with a median time to response of 5.6 versus 11.1 months. The complete response rate was 7% with Niro versus 0% with PBO. Statistically and clinically significant improvements in all prespecified PROs were observed early and sustained on treatment with Niro compared with PBO (Table). Of AEs with Niro, 95% were grade 1/2, the most frequently reported being diarrhea (84%), nausea (54%), fatigue (51%), hypophosphatemia (42%), and maculopapular rash (32%). Ovarian dysfunction occurred in 75% (27/36) of women of childbearing potential in the Niro's arm and resolved in 20 (74%), including 11/11, who discontinued Niro for any reason.


Niro demonstrated statistically and clinically significant improvements in PFS, ORR, symptom burden, physical/role functioning, and health-related quality of life and had a manageable safety profile in adults with progressing DT. DeFi is the most rigorous randomized controlled trial performed in DT and the first positive Phase 3 trial of a GSI in any indication.


European Society for Medical Oncology (ESMO)

ESMO is the leading professional organization for medical oncology. With nearly 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE.


This peer reviewed publication titled Desmoid Tumor Drug Shows Promise was selected for publishing by Disabled World's editors due to its relevance to the disability community. While the content may have been edited for style, clarity, or brevity, it was originally authored by European Society for Medical Oncology and published 2022/09/11 (Edit Update: 2023/09/21). For further details or clarifications, you can contact European Society for Medical Oncology directly at Disabled World does not provide any warranties or endorsements related to this article.

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Cite This Page (APA): European Society for Medical Oncology. (2022, September 11 - Last revised: 2023, September 21). Desmoid Tumor Drug Shows Promise. Disabled World. Retrieved June 14, 2024 from

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