CME
Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™
Released: February 20, 2025
Expiration: August 19, 2025
DeFi: Long-term Follow-up of Nirogacestat for Adults With DTs
DTs, also called desmoid fibromatosis (DF), are a rare disease, affecting approximately 3-5 per 1 million persons each year. Most patients undergo active surveillance for asymptomatic disease and are then treated with systemic therapy (eg, nirogacestat, tyrosine kinase inhibitors, or cytotoxic chemotherapy) or via local control strategies if mass-related symptoms arise.
Nirogacestat is an FDA-approved γ-secretase inhibitor given to patients with progressing DTs who require systemic treatment. Its approval was based on the double-blind, placebo-controlled, randomized phase III DeFi trial in which nirogacestat showed a significant improvement vs placebo in both median PFS (HR: 0.29; P <.001), and in the ORR (41% vs 8%, respectively).1
The primary analysis of the phase III DeFi trial showed that nirogacestat, with a median duration of exposure of 20.6 months (range: 0.3-33.6 months), resulted in significant and clinically meaningful improvements in PFS (primary endpoint), ORR, and QoL-related PROs compared with placebo, and 95% of treatment-emergent adverse events (TEAEs) were grade ≤2, demonstrating the efficacy and safety of nirogacestat for progressing DTs.1
The current analysis of DeFi provided extended follow-up efficacy and safety data for nirogacestat in the treatment of progressing DTs.2
DeFi Long-term Follow-up: Study Design
DeFi was an international, double-blind, placebo-controlled, randomized phase III study in which patients with progressive DTs (defined as disease with progression of ≥20% within 12 months per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) who had not received treatment and were not candidates for surgery, or whose disease had relapsed/regressed after at least 1 line of therapy, were randomized to receive either placebo or nirogacestat 150 mg twice daily.
Patients who were randomized to receive nirogacestat during the double-blind phase were then eligible to transition to the open-label extension phase, where they continued to receive nirogacestat. The primary endpoint was PFS (NCT03785964).1
The current analysis assessed longer-term exposure to nirogacestat and reported the ORR, durability of response to treatment, PROs, and safety after 1-4 years of treatment.2
DeFi Long-term Follow-up: ORR
At the time of this follow-up analysis, the median duration of nirogacestat exposure was 33.6 months (range: 0.3-60 months), which had increased from 20.6 months at the time of the primary analysis. From Year 1 to Year 4, the ORR increased from 34.3% to 45.7%, with patients continuing to respond to nirogacestat. During Years 3 and 4, some patients also had a deepening of response, with 3 new partial responses (PRs) and 3 new complete responses (CRs), for a total of 8 CRs (11.4%) during the 4-year period.2
DeFi Long-term Follow-up: Tumor Size and PROs
The median decrease in tumor size improved each year from Year 1 through Year 4, from a 32.0% reduction from baseline at Year 1 to a 75.8% reduction from baseline at Year 4 in the patients who continued receiving treatment.
Treatment with nirogacestat was also characterized by rapid and sustained improvement in PROs, including average worst pain intensity score, which improved from -1.86 to -1.26; Desmoid Tumor Symptom Scale (DTSS) score, which improved from -1.26 to -0.84; and Desmoid Tumor Impact Scale (DTIS) score, which improved from -0.69 to -0.41. In this analysis, those improvements were sustained over the entire treatment course.2
DeFi Long-term Follow-up: Safety
Of importance, there were no new safety signals with the longer duration of exposure to nirogacestat. The most common TEAEs, regardless of grade, were diarrhea, nausea, fatigue, hypophosphatemia, rash, stomatitis, and headache, and most were grade 1/2 and occurred during the first year of treatment. Moreover, the incidence and severity of TEAEs decreased during Years 2-4.2
DTs have an unpredictable natural history, and it is well described with other treatment options that even after treatment discontinuation, tumor shrinkage can continue. Most patients who were receiving long-term nirogacestat may have continued therapy as part of the clinical trial protocol because the drug was not commercially available, and this was the only way that patients could continue receiving the drug. Although nirogacestat does appear to be safe with long-term therapy, the optimal duration of treatment is currently unknown.
DeFi Long-term Follow-up: Ovarian Toxicity
The reported ovarian toxicities in this longer follow-up of the DeFi trial were consistent with those in the primary analysis. One patient who had not previously noted ovarian toxicity did experience ovarian toxicity, and 3 patients who had prior ovarian toxicity that had resolved experienced another ovarian toxicity event, suggesting that ovarian toxicity is an ongoing event that can occur while patients are receiving treatment.2
DeFi Long-term Follow-up: Conclusions
This long-term follow-up analysis of the DeFi study of adults with progressive DTs who were exposed to nirogacestat for a median duration of 33.6 months showed that continued treatment with nirogacestat further reduced tumor size, offered a durable ORR, and improved PROs.
With these longer-term data, we can see that a subset of patients continues to respond to nirogacestat treatment and some experience a deepening of response over time; however, it is unclear whether continued exposure to nirogacestat is required to see continued tumor shrinkage.
During Years 3 and 4, 3 additional CRs and 3 additional PRs were reported. Moreover, patients reported an early and sustained improvement in pain, symptom severity, and physical functioning.
The safety profile of nirogacestat remained consistent with that in the previous analysis. Therefore, the investigators concluded that the extended use of nirogacestat offers long-term efficacy and safety in patients with progressive DTs.2
Subgroup Analysis of Nirogacestat Efficacy in Patients With DTs and Poor Prognostic Factors
In addition to the longer-term follow-up of the DeFi trial, a post hoc subgroup analysis of nirogacestat efficacy in patients with DTs and disease or patient factors that are often thought to confer a poor prognosis with treatment was presented.
For this subgroup analysis, the authors looked at 4 prognostic factors: tumor size; the presence of genetic mutations; patient age; and the presence of pain at baseline.
A tumor >10 cm in size has been associated with poor local control and low 5-year recurrence-free survival (RFS) rates. Patients with the S45F or T41A mutation in CTNNB1, the gene that encodes catenin-β-1, have demonstrated poor outcomes, especially those with the S45F mutation. It is also widely understood that younger patients (aged 30 years or younger) with DTs often have a higher risk of recurrence and poorer local control. Finally, patients with pain at baseline are often thought to have a higher risk of disease progression and lower event-free survival rates.3
DeFi Subgroup Analysis: PFS by Poor Prognostic Factors
PFS was analyzed according to each of the 4 factors associated with a poor prognosis. Patients across all 4 subgroups treated with nirogacestat experienced fewer PFS events than those treated with placebo. This included an HR of 0.32 (95% CI: 0.13-0.80) for patients with a baseline tumor size of >10 cm, HR of 0.21 (95% CI: 0.08-0.60) in those aged 30 years or younger, HR of 0.18 (95% CI: 0.02-1.46) for those with the S45F mutation in CTNNB1, HR of 0.39 (95% CI: 0.14-1.11) in those with the T41A mutation in CTNNB1, and HR of 0.21 (95% CI: 0.09-0.52) for those with a Brief Pain Inventory–Short Form (BPI-SF) average pain intensity (API) score of >0 at baseline. Baseline pain was defined as the 7-day average of the worse pain during the past 24 hours on a 0-10 scale.3
DeFi Subgroup Analysis: ORR by Poor Prognostic Factors
ORRs were also analyzed according to each of the 4 prognostic factors. Similar to PFS results, ORRs was higher in patients treated with nirogacestat than in those treated with placebo across all 4 subgroups.
In patients with a baseline tumor size of >10 cm, the ORR was 28% with nirogacestat vs 10% with placebo, resulting in an 18.1% difference (95% CI: -0.5% to 36.6%). In patients aged 30 years or younger, the ORR was 40% with nirogacestat vs 4% with placebo, resulting in a 36.3% difference (95% CI: 17.4%-55.2%). In patients with the S45F mutation in CTNNB1, the ORR was 62% with nirogacestat vs 6% with placebo, resulting in a 56.0% difference (95% CI: 27.5%-84.5%). In patients with the T41A mutation in CTNNB1, the ORR was 33% with nirogacestat vs 9% with placebo, resulting in a 24.2% difference (95% CI: 1.9%-46.6%). In patients with a BPI-SF API score of >0 at baseline, the ORR was 43% in the nirogacestat group vs 9% in the placebo group, resulting in a difference of 33.9% (95% CI: 17.5%-50.2%).3
DeFi Subgroup Analysis: PROs for Patients With Large Tumor Size (>10 cm)
Regarding PROs, in the group of patients with large tumors (>10 cm), individuals treated with nirogacestat reported less pain and improved functioning compared with those treated with placebo. Specifically, the average change in API worst pain from baseline at cycle 10 was -1.7 in the nirogacestat group vs -0.4 in the placebo group. The average changes in DTSS and DTIS scores from baseline at cycle 10 were -1.8 and -0.7, respectively, in the nirogacestat group vs 0 and 0.2, respectively, in the placebo group. The average changes in physical functioning, role functioning, and QoL scores from baseline at cycle 10 were 11.9, 11.1, and 8.8, respectively, in the nirogacestat group vs -4.6, -9.6, and -3.2, respectively, in the placebo group.
Here, a negative value indicates an improvement in BPI-SF and Gounder/Desmoid Tumor Research Foundation Desmoid Symptom/Impact Scale (GODDESS) scores, and a positive value indicates an improvement in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) scores.3
DeFi Subgroup Analysis: PROs for Patients With CTNNB1 Mutations
The same was true for patients with the S45F or T41A mutation in the β-catenin gene. Specifically, the average changes in API worst pain from baseline at cycle 10 in patients harboring the S45F mutation and in those harboring the T41A mutation were -2.4 and -2.0, respectively, in the nirogacestat group vs -0.3 and 0.6, respectively, in the placebo group. The average changes in DTSS and DTIS scores from baseline at cycle 10 in patients harboring the S45F mutation and in those harboring the T41A mutation were -1.8 and -1.4 (DTSS) and -1.0 and -0.2 (DTIS), respectively, in the nirogacestat group and 1.4 and 0.1 (DTSS) and 0.5 and 0.4 (DTIS), respectively, in the placebo group. The average changes in physical functioning, role functioning, and QoL scores from baseline at cycle 10 in patients harboring the S45F mutation were 19.2, 16.7, and 17.7, respectively, in the nirogacestat group vs -4.4, -2.8, and -19.4, respectively, in the placebo group. The average changes in physical functioning, role functioning, and QoL scores from baseline at cycle 10 in patients harboring the T41A mutation were 1.8, 9.1, and -7.6, respectively, in the nirogacestat group vs -7.4, -18.5, and -12.0, respectively, in the placebo group.3
DeFi Subgroup Analysis: PROs for Younger Patients (Aged 30 Years or Younger)
The same was also true for patients aged 30 years or younger. Specifically, the average change in API worst pain from baseline at cycle 10 was -2.9 in the nirogacestat group vs -0.2 in the placebo group. The average changes in DTSS and DTIS scores from baseline at cycle 10 were -2.4 and -0.9, respectively, in the nirogacestat group vs 0.7 and 0.3, respectively, in the placebo group. The average changes in physical functioning, role functioning, and QoL scores from baseline at cycle 10 were 7.2, 25.6, and 9.0, respectively, in the nirogacestat group vs -10.5, -9.5, and -20.2, respectively, in the placebo group.3
DeFi Subgroup Analysis: PROs for Patients With Pain at Baseline (BPI-SF API >0)
These trends also held true for patients with pain at baseline. Specifically, the average change in API worst pain from baseline was -2.8 in the nirogacestat group vs -0.6 in the placebo group. The average changes in DTSS and DTIS scores from baseline were -1.8 and -0.9, respectively, in the nirogacestat group vs -0.1 and 0.2, respectively, in the placebo group. The average changes in physical functioning, role functioning, and QoL scores from baseline were 11.2, 21.3, and 12.0, respectively, in the nirogacestat group vs -3.5, -6.9, and -8.8, respectively, in the placebo group.3
DeFi Subgroup Analysis: Conclusions
This post hoc subgroup analysis of the phase III DeFi study showed that patients with poor prognostic factors (tumor size >10 cm, presence of a CTNNB1 mutation, aged 30 years or younger, and pain at baseline) treated with nirogacestat experienced improved PFS, ORR, PROs, and overall QoL vs patients treated with placebo.
The investigators concluded that patients with DT and poor prognostic factors benefit from treatment with nirogacestat.3
This analysis suggests that nirogacestat is a reasonable treatment option, even for this group of patients with DT who historically have been considered less likely to benefit from treatment (eg, surgery, radiation, or systemic therapy).
Retrospective Real-world Study of Nirogacestat in Patients With DTs
One small retrospective study presented at CTOS 2024 provided early real-world experience in patients treated with nirogacestat at a Sarcoma Alliance for Research through Collaboration (SARC) center.4 Retrospective studies with nirogacestat are important because, up until now, the only experience with nirogacestat in the literature were clinical studies, which have very specific patient enrollment criteria. Having some sense of how nirogacestat performs without the constraints of a tightly controlled clinical trial is very helpful.
This analysis included 8 patients from the Soft Tissue Sarcoma Tissue Registry at Roswell Park Comprehensive Cancer Center. Retrospective data were collected by reviewing electronic health records and reported with descriptive analysis and descriptive statistics. Of the 8 patients, 7 were treated with nirogacestat.
Follow-up scans were performed every 3 months, and PRO data were collected and analyzed. The key endpoints were safety and clinical response.4
Real-world Data on Nirogacestat: Patient Characteristics
As one might expect, in this patient population, one half of the patients were female (4 of 8 patients) and a there was a mix of both intra-abdominal and extra-abdominal tumors. Three patients had a history of tumor resection, and all patients had received at least 1 prior therapy, mostly sorafenib. Five of 7 patients received ramp-up dosing of nirogacestat.4
Real-world Data on Nirogacestat: Response
The authors reported clinical response plus pain relief, radiologic response (defined as any decrease in primary tumor size) at 3 months, and measures of disease progression.
Three of the 7 patients experienced a clinical response plus either pain relief or improved QoL, and 4 patients experienced a radiologic response at 3 months on treatment. A 6-month follow-up scan was obtained in 2 patients, and disease progression was noted in 1 patient, although it was unknown whether that patient received a sufficient dose of nirogacestat, because treatment was withheld because of the development of AEs.4
Real-world Data on Nirogacestat: Patient-Level Data
This graph shows the treatment duration and outcome of each patient assessed. Again, 3 patients achieved a clinical response, 3 achieved a radiologic response, and 1 experienced disease progression.
Of importance, the investigators documented that of these 7 patients, 1 menstruating female became pregnant while receiving nirogacestat, which necessitated treatment discontinuation. This study was the first to show that a patient can become pregnant while taking this medicine.
Although it is recommended that patients take active steps to avoid becoming pregnant while receiving this medication, there has been significant concern about ovarian toxicity, because the initial registrational trial noted that this medication may interfere with future childbearing. What these data mean for a deeper understanding of ovarian toxicity is unknown.
It is important to note that there is a more detailed investigation underway assessing nirogacestat-related ovarian toxicity in a prospective fashion. Therefore, expect more information to come. Nevertheless, this real-world experience allows a better understanding of how nirogacestat performs outside the constraints of a clinical trial.4
Real-world Data on Nirogacestat: Safety
These real-world data suggest that the AE profile is similar to what has been described in the DeFi trial, with fatigue, diarrhea, and skin rash being some of the most frequent AEs observed.
Five patients developed upper respiratory tract symptoms, and 1 patient developed visual floaters, necessitating a dose reduction. Other reasons for dose reductions included skin rash, chronic upper respiratory infection, fatigue, and headache.
Also shown here is the maximum tolerated dose (MTD) for each patient. The MTD for nearly one half of the patients was 100 mg in the morning and 150 mg in the evening.4
Real-world Data on Nirogacestat: Conclusions
In this retrospective, real-world study of 7 patients at a SARC center treated with nirogacestat, early responses were observed in most patients at their MTD, although dose reduction and holds were frequently required. Unique AEs included upper respiratory tract symptoms and visual floaters.
In this patient cohort, 1 menstruating female became pregnant during treatment, necessitating discontinuation of nirogacestat.
The investigators concluded that longer-term outcomes from this study as well as a deeper understanding of the impacts of nirogacestat on ovarian reserves in female patients with reproductive potential are needed.4
Population-Based Study of PLD in Patients With Symptomatic DTs
Although there are novel therapies approved for this exceptionally rare disease, in many parts of the world, these more costly treatment options remain inaccessible. For example, nirogacestat is currently approved only in the United States and is available in other places through a compassionate-use, expanded-access program. Sorafenib, which has been around for quite some time, is not universally available.
Older chemotherapeutic agents that are more widely available, such as doxorubicin, PLD, methotrexate, and vinblastine, remain viable options for patients with DTs. Many patients with DTs first undergo active surveillance for asymptomatic disease, and are then treated via systemic therapy or local control strategies in the presence of mass-related symptoms. One population-based study presented at CTOS 2024 explored the clinical outcomes of patients with active, symptomatic DTs who were treated with PLD.5
PLD in DTs: Study Design
This population-based cohort study included 29 patients with active and symptomatic DTs treated at Oslo University Hospital from 2015 to 2023; they received PLD at the standard dose of 40 mg/m2 every 4 weeks for up to 9 cycles. Data assessed in this study included the ORR defined using RECIST v1.1 and the associations among radiologic response, tumor volume, and clinical outcomes.5
PLD in DTs: Baseline Patient Characteristics
As expected, most patients enrolled in this study were young, with an average age of 36 years (range: 18-69 years), were predominantly female, and had varying anatomic tumor locations, including both intra-abdominal and extra-abdominal tumors. The average tumor size was 11.6 cm, ranging from 5.0 to 33.2 cm, and the average tumor volume was 412 mL, ranging from 32 to 8029 mL.
Of note, most patients (72%) did not have familial adenomatous polyposis (FAP), meaning these were sporadic DTs, likely with mutations in the β-catenin gene. However, a relatively high percentage of patients (28%) did have FAP; this may explain why 17% of patients had multifocal DTs, which are more often associated with FAP, although not exclusively.5
PLD in DTs: Patient Disposition and Response
In this study, all 29 patients enrolled received PLD. Among these patients, 26 had symptomatic disease and 22 individuals were initially treated with active surveillance. The median time from diagnosis to active treatment was 6 months (range: 2-171 months), and the median number of PLD cycles was 6 (range: 3-9).
Of importance, most patients treated with PLD responded to treatment by both RECIST, a cross-sectional measurement, and tumor volume, a more sensitive metric of how well a tumor responds to therapy. The ORR was 66%, with 1 patient achieving a CR and 18 patients achieving a PR. The median time to best response was 17 months, with a range of 3-44 months.
More than 93% of patients experienced a reduction in tumor volume, with a median decrease of 78% (range: -99 to 114%). Of the 29 patients enrolled, 19 experienced symptom improvement, all of whom experienced a decrease in tumor size by RECIST.
However, 3 patients developed progressive disease after having an initial response to treatment.5
PLD in DTs: Efficacy
The waterfall plots for best response assessed via RECIST v1.1 (left) and tumor volume (right) are very similar, suggesting concurrence between these endpoints. In fact, a high degree of correlation was observed between percent change in radiologic response using RECIST and tumor volume (r = 0.856; 95% CI: 0.714-0.931).
These data demonstrate, to some extent, what is already known: PLD is a meaningful treatment for patients with DTs, one that may be accessible in many parts of the world.5
PLD in DTs: Summary
This population-based cohort study of patients with DTs showed that PLD treatment resulted in radiologic responses and improved symptoms in most patients (19 of 29), with an ORR of 66% by RECIST v1.1. Moreover, all patients with symptom improvement also experienced a decrease in tumor size.
The investigators concluded that PLD can serve as an effective treatment option in patients with symptomatic DTs.5
Although this treatment can be used in countries where newer therapies are not available, it remains unclear how this therapy compares with novel agents such as nirogacestat and sorafenib.
Multidisciplinary Care of Patients With Primary, Intra-abdominal Desmoid Fibromatosis:
A Single-Institution 30-Year Experience
Intra-abdominal DF occurs in approximately 10% of all DF cases. Severe complications from this condition include bowel obstructions, perforations, and ischemia. Therefore, active observation is not uniformly safe or recommended. Because intra-abdominal DF is rare, data on its incidence, optimal management, and patient outcomes are limited.
A retrospective analysis on multidisciplinary care of patients with primary, intra-abdominal DF was conducted at Memorial Sloan Kettering Cancer Center in New York. The goal of this analysis of a single institution’s experience over 30 years, from 1993 to 2023, was to define patient outcomes among those with primary, intra-abdominal DF after first-line or second-line therapy.6
Multidisciplinary Care of Intra-abdominal Desmoid Fibromatosis: Study Design and Patient Disposition
In total, 155 patients with primary, intra-abdominal DF were treated at Memorial Sloan Kettering Cancer Center between 1993 and 2023 and were identified using a prospectively maintained database and retrospective pathology database queries. The median follow-up for these patients was 61 months. Among the 155 patients, 107 underwent surgical resection, 33 received systemic treatment, and 15 were managed with active surveillance.
The fact that more than two thirds of patients underwent surgical resection is interesting for a few reasons. In general, surgical resection is not recommended for asymptomatic DTs that are not at imminent risk of causing complications; however, it can be difficult to determine which patients with an intra-abdominal DT are at risk for bowel obstruction, fistula, and ischemia. Because of this, many healthcare professionals recommend treatment sooner for patients with intra-abdominal tumors. These patients were also treated between 1993 and 2023, and the preference for avoiding surgery has only become standard practice mainly during the past 5-10 years.
Among the 33 patients who received systemic therapy, 21 were treated with liposomal doxorubicin and 12 were given another therapy. Fifteen patients underwent active surveillance, which is in keeping with the more modern management paradigm, while recognizing that because of the potential for complications with intra-abdominal tumors, there is sometimes less comfort with active surveillance.6
Multidisciplinary Care of Intra-abdominal Desmoid Fibromatosis: Baseline Characteristics
The baseline characteristics suggest a slightly older patient population than in the other studies we have discussed, with an average age of 56 years in the entire cohort. There was also less of a female predominance in this group (47.1% of patients) compared with the other studies we have discussed.
These intra-abdominal tumors involved different structures within the abdomen, with 32.3% localized in the jejunum and 28.4% localized in the ileum. Nearly one half of all patients who were treated with surgery had a tumor located in the jejunum (45.8%), whereas 40% of patients who were treated with active surveillance had a tumor located in the ileum.
There was a significant difference in both age (P <.01) and tumor location (P <.01) by primary treatment, but the difference in sex by primary treatment was not significant (P = .702).6
Multidisciplinary Care of Intra-abdominal Desmoid Fibromatosis: Baseline Characteristics
This table shows additional baseline characteristics, including the presence or absence of FAP, tumor complications, tumor size, and tumor category.
Among all 155 patients, 9% had FAP, including 5.6% of patients who were treated with surgery; 21.2% of those who were treated with systemic therapy; and 6.7% of those who were treated with active surveillance.
Most patients (91%) did not experience tumor complications; among those who did, 3.9% experienced obstruction; 3.2% experienced perforation; and 1.9% experienced fistulization. Most patients who did have tumor complications received surgery (n = 10), whereas the remaining received systemic therapy (n = 4).
The average tumor size, regardless of the treatment group, ranged from 6.2 cm to 11.3 cm. More than 40% of patients in this analysis had a tumor size of >10 cm, and 54.5% of individuals treated with systemic therapy were in this subgroup of patients. In total, 22.6% of patients had a tumor size of <5 cm, and 46.7% of patients who underwent active surveillance were in this subgroup.
The choice of treatment was associated with the site of the tumor, tumor size, patient age, and an underlying diagnosis of FAP.6
Multidisciplinary Care of Intra-abdominal Desmoid Fibromatosis: PFS and RFS
Surgery is often discouraged as a treatment for DTs because of issues such as resection of large amounts of bowel, pain associated with surgery, and a lack of symptom improvement; however, PFS can be quite good in patients who have undergone complete microscopic resection. This is illustrated in this 5-year RFS rate of 81% and is consistent with other surgical experiences with DT control rates of 70% to 80%.7
A tumor size of >10 cm or patient age of less than 45 years were statistically associated with higher local recurrence rates after resection (HR: 1.7; P = .3 or HR: 2.2; P = .1, respectively).
For patients who received systemic therapy with liposomal doxorubicin, the 5-year PFS rate was 67%, and 70% of patients experienced a reduction in tumor size.
I want to point out that first-line systemic therapy included liposomal doxorubicin in 61% of patients, tyrosine kinase inhibitors in 18% of patients, and methotrexate-based regimens in 6% of patients in this study. These results suggest that frontline therapy with liposomal doxorubicin is quite effective, and that for many patients, treatment with liposomal doxorubicin results in sustained response without progression.6
Multidisciplinary Care of Intra-abdominal Desmoid Fibromatosis: Investigator’s Conclusions
In this long-term, single-institution study, patients with primary, intra-abdominal DF treated with surgery or systemic therapy experienced durable responses, with a 5-year PFS rate of 67% among those who received liposomal doxorubicin. Surgery was associated with a lower recurrence risk among those who underwent R0/R1 resection, with a 5-year RFS rate of 81%.
The investigators concluded that variable interventions are necessary because of anatomic constraints and the risk of complications associated with the growth of primary, intra-abdominal DF. Therefore, a tailored and multidisciplinary approach to care is necessary to manage patients with this disease.6
Future Directions With DT Care
At present, wonderful novel agents for this exceptionally rare disease are becoming available. In addition to nirogacestat, a second γ-secretase inhibitor, AL102, is currently the subject of the phase II/III RINGSIDE study (NCT04871282). However, issues remain regarding access to and the cost of novel treatments. For example, nirogacestat is not yet available in most parts of the world. Thus, there is still a need for understanding how best to use other, more widely available treatment options until these novel agents are available to all patients.
There continues to be considerable effort in educating healthcare professionals that active surveillance is recommended for the vast majority of patients with asymptomatic DTs and that surgery is often not necessary for patients, even those with symptomatic DTs—particularly as we gain access to novel treatments that are likely to improve patients’ symptoms and result in tumor shrinkage. With these systemic therapies, avoiding surgical interventions may help to improve patients’ QoL, with less pain from nonsurgical interventions.
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