Efficacy and tolerability of trabectedin in elderly patients with sarcoma: subgroup analysis from a phase III, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma

Jones, Robin L.; Demetri, George D.; Schuetze, Scott M.; Milhem, Mohammed; Elias, Anthony; Tine, Brian Andrew Van; Hamm, John; McCarthy, Sharon; Wang, G.; Parekh, Trilok; Knoblauch, Roland; Hensley, Martee L.; Maki, Robert G.; Patel, Shreyaskumar; Mehren, Margaret von

doi:10.1093/annonc/mdy253

Cited by 35 publications

(26 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Once again, this finding is consistent with the subgroup analysis of the ET743-SAR-3007 trial, which showed comparable benefit and safety for trabectedin in patients aged ≥65 years. 27 One of the exploratory endpoints of this trial was to investigate the pharmacokinetics of trabectedin. To the best of our knowledge, this is the first study to specifically assess pharmacokinetics in such an elderly population.…”

Section: Figurementioning

confidence: 99%

Pharmacokinetics, safety, and activity of trabectedin as first‐line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group

Grosso

D’Ambrosio

Zucchetti

et al. 2020

Cancer

View full text Add to dashboard Cite

BACKGROUND: Although elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline-based chemotherapy. Trabectedin is registered as a second-line treatment for advanced STS and is characterized by a favorable safety profile. METHODS: The aim of this single-arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3-1.5 mg/m 2) as a first-line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline-based chemotherapy. The coprimary endpoints were progression-free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics. RESULTS: Twenty-four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74-83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3-6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%-81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%-57%]) experienced CLTs. Trabectedin C max , half-life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m 2 (SD, 14.08 L/h/m 2), and 1460 L/m 2 (SD, 561 L/m 2), respectively. CONCLUSION: Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data.

show abstract

Section: Figurementioning

confidence: 99%

Pharmacokinetics, safety, and activity of trabectedin as first‐line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group

Grosso

D’Ambrosio

Zucchetti

et al. 2020

Cancer

View full text Add to dashboard Cite

show abstract

“…An age >65 years was associated with significantly higher hematological toxicity in a multivariate analysis. Moreover, investigators' general conservative approach in terms of increasing the rate of discontinuation due to drug-related AEs in treating elderly population cannot be ruled out as reported by some authors [28].…”

Section: Wide R0 Surgerymentioning

confidence: 98%

“…Outcome, safety, and tolerability of medical treatments in elderly patients with STS have been the subject of a series of retrospective subgroup analyses in clinical trials including all ages [27,28]. The invariable message of these analyses was that the elderly population has similar outcomes when compared with younger ones when active treatments are employed at the cost of an augmented toxicity that would require an age customization schedule and a careful selection of patients.…”

Section: Wide R0 Surgerymentioning

confidence: 99%

The Real-Life Journey of Elderly Patients in Soft Tissue and Bone Sarcomas: A Retrospective Analysis from a Sarcoma Referral Center

Ferraresi

Vari

Rossi

et al. 2020

JCM

View full text Add to dashboard Cite

The high complexity of multimodality treatment frequently results in undertreatment of elderly sarcoma patients, and this may be one of the factors that influence their prognosis. We describe the real-life approach to a population of patients aged over 70 with both soft tissue (STS) and bone sarcomas (BS) followed by our Sarcoma Disease Management Team from 2012 to 2017. One-hundred and twenty-three patients with a median age of 77 years (range: 70–92) were identified. STS were the most common histological subtypes (94%) and the grade was high in 79/123 patients (64%). At diagnosis, 88% of patients had localized disease (LD) and 12% were metastatic (MD). Overall, 96% of patients with LD underwent surgery, 46/54 (85%) with high grade STS patients underwent complementary radiotherapy, and 10/54 (19%) received adjuvant treatments. Twelve out of 33 patients who relapsed (36%) underwent local therapies. Seventeen (52%) and eight (24%) patients were treated with first-line and second-line medical treatments, respectively. Tolerability to systemic treatments was fairly good. Overall, 21% of the patients with advanced disease were candidates for best supportive care alone. Our case series of elderly patients with both STS and BS shows that personalized multidisciplinary treatment can nevertheless be offered to this frail population in order to control the evolution of disease.

show abstract

“…Furthermore, the safety profile for elderly patients treated with trabectedin was similar to that in the overall study population treated with trabectedin. 93…”

Section: Treatment For Rpss With Elderly Patientsmentioning

confidence: 99%

Retroperitoneal tumors: Review of diagnosis and management

Sassa

2020

Int J of Urology

View full text Add to dashboard Cite

Retroperitoneal tumors are extremely rare tumors occurring in the retroperitoneum. Retroperitoneal tumors are divided into benign tumors and malignant tumors, including retroperitoneal sarcoma. Approximately 70-80% of primary retroperitoneal soft-tissue tumors are malignant; however, these only account for 0.1-0.2% of all malignancies. Retroperitoneal sarcoma is an orphan malignant disease with a low incidence. The information on benign retroperitoneal tumors is limited. The American Joint Committee on Cancer/TNM classification updated to the 8th edition in 2017. In 2010, three new drugs for soft tissue sarcoma were approved based on the results of phase III trials, but the histological subtypes of the patients enrolled in the trials of each drug differed. Recently, in addition to surgery for retroperitoneal sarcoma, the effectiveness of perioperative radiation therapy has become interesting. For malignant retroperitoneal tumors and retroperitoneal sarcoma, survival improvement and locoregional recurrence prevention can be undertaken by carrying out surgery to secure negative margins with wide and combined resection of some adjacent organs, and cooperation with a trained medical team comprising of radiologists, pathologists and medical oncologists in centralized hospitals. Some clinical trials aimed at further improving treatment results by adding preoperative chemotherapy and radiation therapy based on histological confirmation using a correct needle biopsy are in progress. In recent years, molecular profiling has been used to select eligible patients for chemotherapy. In the future, precision medicine with next-generation sequencing technology will be expected among the diverse and potential future treatments for retroperitoneal sarcoma. In this review, we summarized the current state of retroperitoneal tumors and retroperitoneal sarcoma.

show abstract

Efficacy and tolerability of trabectedin in elderly patients with sarcoma: subgroup analysis from a phase III, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma

Abstract: www.clinicaltrials.gov, NCT01343277.

Cited by 35 publications

References 22 publications

Pharmacokinetics, safety, and activity of trabectedin as first‐line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group

Pharmacokinetics, safety, and activity of trabectedin as first‐line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group

The Real-Life Journey of Elderly Patients in Soft Tissue and Bone Sarcomas: A Retrospective Analysis from a Sarcoma Referral Center

Retroperitoneal tumors: Review of diagnosis and management

Contact Info

Product

Resources

About