Safety of 177Lu-DOTATATE in patients with advanced neuroendocrine tumors: Data from a U.S. expanded access program.

4604 Background: The NETTER-1 clinical trial showed that peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE increased progression-free survival in patients with somatostatin-receptor-positive advanced midgut neuroendocrine tumors (NETs) compared with high-dose octreotide long-acting repeatable, and was associated with few serious adverse events (AEs). To assess the safety profile of 177Lu-DOTATATE in a real-world population, we analyzed safety data from a US expanded access program (NCT02705313). Methods: Patients had inoperable, histologically proven, somatostatin-receptor-positive, locally advanced or metastatic GEPNETs (Ki-67 index ≤ 20%) that progressed after somatostatin analog therapy. Exclusion criteria were: surgery, radiotherapy or chemotherapy in the last 12 weeks; treatment with an interferon, mTOR inhibitor, or other systemic therapy in the last 4 weeks; or ongoing octreotide therapy that could not be interrupted for PRRT. Patients with impaired renal function (serum creatinine > 1.7 mg/dL or creatinine clearance < 50 mL/min) or serious coexisting conditions were excluded. The analysis included patients who received ≥ 1 cycle of 177Lu-DOTATATE between July 5, 2016 and December 21, 2018. Data were collected from the first cycle to the latest data collection point (up to October 7, 2019). Results: 299 patients received a mean 177Lu-DOTATATE cumulative dose of 552 mCi (20.4 GBq) (standard deviation [SD]: 220 mCi [8.1 GBq]) over a mean of 2.8 cycles (SD: 1.1). Mean age was 60.8 years (SD: 11.7); 38.5% of patients were men. Over a mean follow-up of 131 days (SD: 87), 48.8% of patients reported treatment-related AEs (TRAEs), with a maximum severity of grade 1, 2 and 3 for 26.8% (n = 80), 18.1% (n = 54) and 4.0% (n = 12) of patients, respectively; there were no grade 4–5 TRAEs. The most common TRAEs of any grade (≥ 5.0% of patients) were nausea (31.1%), vomiting (13.7%), fatigue (9.4%) and thrombocytopenia (6.0%). The most prevalent grade 3 TRAEs were lymphocyte count decrease (1.0%) and thrombocytopenia (0.7%). Serious TRAEs occurred in 1.0% of patients (carcinoid crisis, dehydration, syncope and vomiting). AEs led to dose modification in 1.7% of patients, dose delay in 6.4% (most commonly due to nausea [2.0%] or thrombocytopenia [2.0%]) and discontinuation in 1.3% (due to thrombocytopenia [1.0%] and extravasation [0.3%]). Conclusions: In a real-world population of US patients with advanced GEPNETs, 177Lu-DOTATATE treatment was well tolerated with few TRAEs, consistent with the safety profile in the NETTER-1 trial. Clinical trial information: NCT02705313 .

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Spanish experience with the ipilimumab Expanded Access Program.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19023 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19023-e19023 ◽

Cited By ~ 2

Author(s):

Alfonso Berrocal ◽

Jose A. Lopez-Martin ◽

Ana Maria Arance ◽

V. Soriano ◽

Enrique Espinosa ◽

...

Keyword(s):

Clinical Trial ◽

Performance Status ◽

High Dose ◽

Ecog Performance Status ◽

Expanded Access ◽

Expanded Access Program ◽

Grade Ii ◽

One Year ◽

Access Program ◽

Grade Iii

e19023 Background: Second line ipilimumab has proven efficacy in clinical trial but few is known outside this setting. Methods: We have retrospectively reviewed experience with the Expanded Access Program for Ipilimumab in Spain. We have collected data on demographics, response survival and toxicity. Ipilimumab was administered at a 3 mg/kg dose for four induction courses. Results: We have retrieved 99 expanded access ipilimumab applications that represent 40% of all possible applications. Five patients are not evaluable because they never received ipilimumab 4 due to progression and 1 declined consent. Median age is 58.5 years (30-81) and 54.3% of the patients are males. 59.6% have 3 or more metastatic locations, 50% have liver metastases, 16% have CNS metastasis and 74.6% have elevated LDH. ECOG performance status was 0 to 1 in 91.9%. Previous adyuvant treatment was received by 43.6% of the patients and consisted in high dose interferon in 85.4%. All except one patient have received previous first line chemotherapy and 34.2% have received 2 or more chemotherapy lines. Medium time from the start of metastatic disease to the start of ipilimumab was 11.2 months. 58.5% of the patients completed 4 doses of ipilimumab main reason for not completion was death or progression in 84.6% and toxicity in 5.1%. 8 patients are not evaluable for response, 5 have just completed the treatment and 3 are still on treatment. Responses are 1 (1.1%) CR, 6 (6.4%) PR, 6 (6.4%) PR with previous progression or new lesions, 13 (13.8%) SD, and 60 (63.8%) progressive disease. Reinduction treatment was offered to 5 patients 2 PR patients achieved a new PR, one PR patients a SD and 2 SD patients progressed after reinduction. Kaplan and Meier median survival is 150 days (95% CI 110,5-189.4). One year survival is 32.4% and 18 months survival 21.6%. Toxicity has been mild, skin, 20.2% grade I and 5.3% grade II, liver 7.4% grade I, 2.1% grade II, 3.2 grade III, and diarrhea 19.1% gI, 3.2% grade II and 1.1% grade IV. Only 7 patients experienced toxicity grade III to IV. Conclusions: Ipilimumab efficacy when it is used outside clinical trial is similar to the reported. There is room for improvement in patient selection as 40% of them did not completed treatment. Toxicity of the 3 mg/kg schedule is mild.

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REACT expanded-access program in patients with metastatic renal cell carcinoma: real-world data from a European subanalysis

Future Oncology ◽

10.2217/fon.15.241 ◽

2015 ◽

Vol 11 (21) ◽

pp. 2893-2903 ◽

Cited By ~ 2

Author(s):

Sergio Bracarda ◽

Sylvie Rottey ◽

Amit Bahl ◽

Christian Eichelberg ◽

Begoña Mellado ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Real World ◽

Renal Cell ◽

Real World Data ◽

World Data ◽

Expanded Access ◽

Expanded Access Program ◽

Access Program

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The use of nusinersen in the “real world”: the UK and Ireland experience with the expanded access program (EAP)

Neuromuscular Disorders ◽

10.1016/s0960-8966(18)30364-x ◽

2018 ◽

Vol 28 ◽

pp. S25 ◽

Cited By ~ 1

Author(s):

M. Scoto ◽

A. Manzur ◽

M. Main ◽

P. Munot ◽

R. Tillmann ◽

...

Keyword(s):

Real World ◽

The Real ◽

Expanded Access ◽

Expanded Access Program ◽

The Uk ◽

Access Program

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1074P Italian nivolumab Expanded Access Program (EAP) in melanoma adjuvant setting: Patients outcomes and safety profile

Annals of Oncology ◽

10.1016/j.annonc.2021.08.1459 ◽

2021 ◽

Vol 32 ◽

pp. S890-S891

Author(s):

M. Del Vecchio ◽

A.M. Di Giacomo ◽

P. Quaglino ◽

V. Chiarion Sileni ◽

P. Queirolo ◽

...

Keyword(s):

Safety Profile ◽

Adjuvant Setting ◽

Expanded Access ◽

Expanded Access Program ◽

Access Program

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Safety of trifluridine/tipiracil for metastatic colorectal cancer in African American patients participating in an expanded access program.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15039 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15039-e15039

Author(s):

Philip Agop Philip ◽

Brandon George Smaglo ◽

Bassel F. El-Rayes ◽

Christian Lesuisse ◽

Lukas Makris

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

African American ◽

Metastatic Colorectal Cancer ◽

Performance Status ◽

Drug Discontinuation ◽

Open Label ◽

Expanded Access ◽

Expanded Access Program ◽

Access Program

e15039 Background: A Phase 3 clinical trial (RECOURSE) showed that trifluridine/tipiracil (FTD/TPI) was effective in the treatment of refractory metastatic colorectal cancer (mCRC) (Mayer et al. NEJM 2015;372:1909-19). An expanded-access program (EAP) for patients with refractory mCRC assessed FTD/TPI safety in a real-world setting. One limitation of RECOURSE was the small number of African-American (AA) patients enrolled in the study (n=8). The EAP enrolled 45 AA patients, enabling assessment of FTD/TPI safety in this population. Methods: Patients aged ≥18 years with refractory mCRC resistant to ≥2 regimens of standard chemotherapy and an ECOG performance status of 0 or 1 were enrolled in this open-label EAP. Patients received FTD/TPI 35 mg/m2 twice daily for 5 days followed by 2 days’ rest repeated twice followed by 14 days’ rest over a 28-day treatment cycle until drug discontinuation. We investigated duration of exposure to FTD/TPI and associated adverse events (AEs) in AA patients to compare them with non-AA and US patients from RECOURSE. Results: Median duration of FTD/TPI therapy for AA patients in the EAP was 9.7 weeks, similar to non-AA patients in the EAP (9.7 weeks) and US patients in RECOURSE (8.9 weeks) (differences not statistically significant). 73.3% of AA patients (n=33) in the EAP discontinued treatment due to disease progression and 8.9% (n=4) discontinued due to AEs. AEs related to FTD/TPI are summarized in the table. Conclusions: Lung cancer patients in Eastern North Carolina possess a strikingly poor inflammatory signature with significant implications for quality of life and survival. Clinical trial information: NCT02286492. [Table: see text]

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GECP 1605/NIVEX TRIAL nivolumab in the real world: The SPANISH expanded access program experience in pretreated advanced NSCLC

Annals of Oncology ◽

10.1093/annonc/mdy292.090 ◽

2018 ◽

Vol 29 ◽

pp. viii531

Author(s):

M. Majem Tarruella ◽

J. Campillo ◽

J.F. Grau Béjar ◽

E. Carcereny ◽

R. Bernabe Caro ◽

...

Keyword(s):

Real World ◽

Advanced Nsclc ◽

The Real ◽

Expanded Access ◽

Expanded Access Program ◽

Access Program

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Erdafitinib treatment in Brazilian patients with metastatic urothelial carcinoma (mUC): real-world evidence from an Expanded Access Program

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211015499 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110154

Author(s):

Fernando Sabino M. Monteiro ◽

Adriano Gonçalves e Silva ◽

Andrea Juliana P. de S. Gomes ◽

Carolina Dutra ◽

Naira Oliveira Ferreira ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Real World ◽

Objective Response ◽

Significant Activity ◽

Efficacy And Safety ◽

Expanded Access ◽

Expanded Access Program ◽

Real World Evidence ◽

Metastatic Urothelial Carcinoma ◽

Access Program

Background: Erdafitinib is the first targeted therapy approved for the treatment of patients with metastatic urothelial carcinoma (mUC). Approval was based on a phase II single-arm trial that demonstrated significant activity of erdafitinib in patients with tumors harboring FGFR2/3 alterations. In Brazil, an Expanded Access Program (EAP) provided patients with early access to erdafitinib prior to market authorization. The current report describes characteristics and outcomes of patients with mUC on erdafitinib therapy. Methods: Patients with mUC that failed first- and second-line systemic therapies were screened for FGFR2/3 alterations in primary or metastatic tumor tissues. Patients with FGFR2/3 alterations were selected to receive erdafitinib at the standard dosing schedule and were followed prospectively to evaluate the efficacy and safety outcomes. Results: From 19 April 2019, through 13 March 2020, 47 patients with mUC from 10 Brazilian centers were tested for FGFR2/3 alterations. Alterations in FGFR2/3 were found in 12 patients (25.5%) and all of them were eligible for the EAP. Four patients (33%) had partial response, while two patients (17%) had stable disease. Progressive disease, the best response, was observed in five patients (42%). At a median follow-up of 16.2 months, the median time to treatment failure (TTF) was 2.8 months. When considering only patients with objective response, the median TTF was 5.3 months. Adverse events (AEs) were reported for any grade and grade 3 or higher in 10 patients (83%) and 5 patients (42%), respectively. The most common AE was hyperphosphatemia. Conclusion: This first real-world evidence report of heavily treated patients with mUC confirms the efficacy and safety of erdafitinib in a disease setting with a lack of treatment options.

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