NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC).

Mairead Mcnamara; Jayne Swain; Zoe Craig; Rohini Sharma; Olusola Faluyi; Jonathan Wadsley; Carys Morgan; Lucy R Wall; Ian Chau; Nick Reed; Debashis Sarker; Jane Margetts; Daniel Krell; Judith Cave; Sharmila Sothi; Alan Anthoney; Alkesh Patel; Angela Lamarca; Richard A Hubner; Juan W Valle

Abstract

Background: As demonstrated in the primary analysis of NET-02, nal-IRI/5-FU/folinic acid, but not docetaxel, met the primary endpoint of 6 month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC. Here, the final results are presented.
Methods: This was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI (70mg/m2 free base)/5-FU (2400 mg/m2)/folinic acid, Q14 days (ARM A), or IV docetaxel (75mg/m2), Q21 days (ARM B), as 2L therapy in pts with progressive PD-EP-NEC, aimed at selecting a treatment for continuation to a phase III trial. On disease progression, pts in both arms could receive further systemic treatment as recommended by their physicians. Primary endpoint was 6 mo PFS rate; 80% power to demonstrate the one-sided 95% confidence interval (CI) of the 6 mo PFS rate excluded 15%, if the true rate was ≥30% (required level of efficacy); a rate of Results: Of 58 pts in 15 UK centres (Nov 18-Dec 21), 29 in ARM A (2 pts excluded for efficacy analysis: well-differentiated grade 3 (G3) neuroendocrine tumour and goblet cell adenocarcinoma), 29 in ARM B. Eight pts in both arms (27.6% each) received subsequent chemotherapy. Fifty-four pts (93%) have died; the primary end-point of 6-mo PFS rate was met in ARM A; ORR, median PFS and OS are also presented (Table). Adverse events ≥ G3 occurred in 51.7% and 55.2% in ARM A and B with 1 and 6 discontinuations due to toxicity in ARM A and B, respectively. Health-related QoL was maintained (C30 functional scales & global health status remained stable pre-progression) and potentially improved (sustained improvement in role functioning) with nal-IRI/5-FU/folinic acid, but not docetaxel (all C30 functional scales & global health status worsened between baseline and week 18, and treatment-related symptoms also worsened in GINET21). Translational analysis is on-going.
Conclusion: nal-IRI/5-FU warrants further evaluation in pts with PD-EP-NEC, with the results highlighting that conduct of randomised trials in this disease group of unmet need is possible and safe.

ARM A (N=27) nal-IRI/5-FU, ARM B (N=29) Docetaxel
6 mo PFS rate (%) 29.6 (lower 95% CI 15.68), 13.8 (lower 95% CI 4.85)
ORR (%) 11.1 (95% CI 2.4-29.2), 10.3 (95% CI 2.2-27.4)
Median PFS (mo) 3 (95% CI 2-6), 2 (95% CI 2-2)
Median OS (mo) 6 (95% CI 3-10), 6 (95% CI 3-9)

Original language	English
Publication status	Published - 2023
Event	ASCO GI 2023 - San Francisco, San Francisco, United States Duration: 19 Jan 2023 → 21 Jan 2023 https://ascopubs.org/doi/pdf/10.1200/JCO.2023.41.4_suppl.646?role=tab

Conference

Conference	ASCO GI 2023
Country/Territory	United States
City	San Francisco
Period	19/01/23 → 21/01/23
Internet address	https://ascopubs.org/doi/pdf/10.1200/JCO.2023.41.4_suppl.646?role=tab

Keywords

Second-line
chemotherapy
extra-pulmonary
Neuroendocrine carcinoma

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Mcnamara, M., Swain, J., Craig, Z., Sharma, R., Faluyi, O., Wadsley, J., Morgan, C., Wall, L. R., Chau, I., Reed, N., Sarker, D., Margetts, J., Krell, D., Cave, J., Sothi, S., Anthoney, A., Patel, A., Lamarca, A., Hubner, R. A., & Valle, J. W. (2023). NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC).. Abstract from ASCO GI 2023, San Francisco, United States.

Mcnamara, Mairead ; Swain, Jayne ; Craig, Zoe et al. / NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC). Abstract from ASCO GI 2023, San Francisco, United States.

@conference{d7342df95ba14c38903d28b13872121e,

title = "NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC).",

abstract = "Background: As demonstrated in the primary analysis of NET-02, nal-IRI/5-FU/folinic acid, but not docetaxel, met the primary endpoint of 6 month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC. Here, the final results are presented.Methods: This was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI (70mg/m2 free base)/5-FU (2400 mg/m2)/folinic acid, Q14 days (ARM A), or IV docetaxel (75mg/m2), Q21 days (ARM B), as 2L therapy in pts with progressive PD-EP-NEC, aimed at selecting a treatment for continuation to a phase III trial. On disease progression, pts in both arms could receive further systemic treatment as recommended by their physicians. Primary endpoint was 6 mo PFS rate; 80% power to demonstrate the one-sided 95% confidence interval (CI) of the 6 mo PFS rate excluded 15%, if the true rate was ≥30% (required level of efficacy); a rate of Results: Of 58 pts in 15 UK centres (Nov 18-Dec 21), 29 in ARM A (2 pts excluded for efficacy analysis: well-differentiated grade 3 (G3) neuroendocrine tumour and goblet cell adenocarcinoma), 29 in ARM B. Eight pts in both arms (27.6% each) received subsequent chemotherapy. Fifty-four pts (93%) have died; the primary end-point of 6-mo PFS rate was met in ARM A; ORR, median PFS and OS are also presented (Table). Adverse events ≥ G3 occurred in 51.7% and 55.2% in ARM A and B with 1 and 6 discontinuations due to toxicity in ARM A and B, respectively. Health-related QoL was maintained (C30 functional scales & global health status remained stable pre-progression) and potentially improved (sustained improvement in role functioning) with nal-IRI/5-FU/folinic acid, but not docetaxel (all C30 functional scales & global health status worsened between baseline and week 18, and treatment-related symptoms also worsened in GINET21). Translational analysis is on-going.Conclusion: nal-IRI/5-FU warrants further evaluation in pts with PD-EP-NEC, with the results highlighting that conduct of randomised trials in this disease group of unmet need is possible and safe. ARM A (N=27) nal-IRI/5-FU, ARM B (N=29) Docetaxel6 mo PFS rate (%) 29.6 (lower 95% CI 15.68), 13.8 (lower 95% CI 4.85)ORR (%) 11.1 (95% CI 2.4-29.2), 10.3 (95% CI 2.2-27.4)Median PFS (mo) 3 (95% CI 2-6), 2 (95% CI 2-2)Median OS (mo) 6 (95% CI 3-10), 6 (95% CI 3-9)",

keywords = "Second-line, chemotherapy, extra-pulmonary, Neuroendocrine carcinoma",

author = "Mairead Mcnamara and Jayne Swain and Zoe Craig and Rohini Sharma and Olusola Faluyi and Jonathan Wadsley and Carys Morgan and Wall, {Lucy R} and Ian Chau and Nick Reed and Debashis Sarker and Jane Margetts and Daniel Krell and Judith Cave and Sharmila Sothi and Alan Anthoney and Alkesh Patel and Angela Lamarca and Hubner, {Richard A} and Valle, {Juan W}",

year = "2023",

language = "English",

note = "ASCO GI 2023 ; Conference date: 19-01-2023 Through 21-01-2023",

url = "https://ascopubs.org/doi/pdf/10.1200/JCO.2023.41.4_suppl.646?role=tab",

}

Mcnamara, M, Swain, J, Craig, Z, Sharma, R, Faluyi, O, Wadsley, J, Morgan, C, Wall, LR, Chau, I, Reed, N, Sarker, D, Margetts, J, Krell, D, Cave, J, Sothi, S, Anthoney, A, Patel, A, Lamarca, A, Hubner, RA & Valle, JW 2023, 'NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC).', ASCO GI 2023, San Francisco, United States, 19/01/23 - 21/01/23.

NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC). / Mcnamara, Mairead; Swain, Jayne; Craig, Zoe et al.
2023. Abstract from ASCO GI 2023, San Francisco, United States.

Research output: Contribution to conference › Abstract › peer-review

TY - CONF

T1 - NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC).

AU - Mcnamara, Mairead

AU - Swain, Jayne

AU - Craig, Zoe

AU - Sharma, Rohini

AU - Faluyi, Olusola

AU - Wadsley, Jonathan

AU - Morgan, Carys

AU - Wall, Lucy R

AU - Chau, Ian

AU - Reed, Nick

AU - Sarker, Debashis

AU - Margetts, Jane

AU - Krell, Daniel

AU - Cave, Judith

AU - Sothi, Sharmila

AU - Anthoney, Alan

AU - Patel, Alkesh

AU - Lamarca, Angela

AU - Hubner, Richard A

AU - Valle, Juan W

PY - 2023

Y1 - 2023

N2 - Background: As demonstrated in the primary analysis of NET-02, nal-IRI/5-FU/folinic acid, but not docetaxel, met the primary endpoint of 6 month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC. Here, the final results are presented.Methods: This was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI (70mg/m2 free base)/5-FU (2400 mg/m2)/folinic acid, Q14 days (ARM A), or IV docetaxel (75mg/m2), Q21 days (ARM B), as 2L therapy in pts with progressive PD-EP-NEC, aimed at selecting a treatment for continuation to a phase III trial. On disease progression, pts in both arms could receive further systemic treatment as recommended by their physicians. Primary endpoint was 6 mo PFS rate; 80% power to demonstrate the one-sided 95% confidence interval (CI) of the 6 mo PFS rate excluded 15%, if the true rate was ≥30% (required level of efficacy); a rate of Results: Of 58 pts in 15 UK centres (Nov 18-Dec 21), 29 in ARM A (2 pts excluded for efficacy analysis: well-differentiated grade 3 (G3) neuroendocrine tumour and goblet cell adenocarcinoma), 29 in ARM B. Eight pts in both arms (27.6% each) received subsequent chemotherapy. Fifty-four pts (93%) have died; the primary end-point of 6-mo PFS rate was met in ARM A; ORR, median PFS and OS are also presented (Table). Adverse events ≥ G3 occurred in 51.7% and 55.2% in ARM A and B with 1 and 6 discontinuations due to toxicity in ARM A and B, respectively. Health-related QoL was maintained (C30 functional scales & global health status remained stable pre-progression) and potentially improved (sustained improvement in role functioning) with nal-IRI/5-FU/folinic acid, but not docetaxel (all C30 functional scales & global health status worsened between baseline and week 18, and treatment-related symptoms also worsened in GINET21). Translational analysis is on-going.Conclusion: nal-IRI/5-FU warrants further evaluation in pts with PD-EP-NEC, with the results highlighting that conduct of randomised trials in this disease group of unmet need is possible and safe. ARM A (N=27) nal-IRI/5-FU, ARM B (N=29) Docetaxel6 mo PFS rate (%) 29.6 (lower 95% CI 15.68), 13.8 (lower 95% CI 4.85)ORR (%) 11.1 (95% CI 2.4-29.2), 10.3 (95% CI 2.2-27.4)Median PFS (mo) 3 (95% CI 2-6), 2 (95% CI 2-2)Median OS (mo) 6 (95% CI 3-10), 6 (95% CI 3-9)

AB - Background: As demonstrated in the primary analysis of NET-02, nal-IRI/5-FU/folinic acid, but not docetaxel, met the primary endpoint of 6 month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC. Here, the final results are presented.Methods: This was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI (70mg/m2 free base)/5-FU (2400 mg/m2)/folinic acid, Q14 days (ARM A), or IV docetaxel (75mg/m2), Q21 days (ARM B), as 2L therapy in pts with progressive PD-EP-NEC, aimed at selecting a treatment for continuation to a phase III trial. On disease progression, pts in both arms could receive further systemic treatment as recommended by their physicians. Primary endpoint was 6 mo PFS rate; 80% power to demonstrate the one-sided 95% confidence interval (CI) of the 6 mo PFS rate excluded 15%, if the true rate was ≥30% (required level of efficacy); a rate of Results: Of 58 pts in 15 UK centres (Nov 18-Dec 21), 29 in ARM A (2 pts excluded for efficacy analysis: well-differentiated grade 3 (G3) neuroendocrine tumour and goblet cell adenocarcinoma), 29 in ARM B. Eight pts in both arms (27.6% each) received subsequent chemotherapy. Fifty-four pts (93%) have died; the primary end-point of 6-mo PFS rate was met in ARM A; ORR, median PFS and OS are also presented (Table). Adverse events ≥ G3 occurred in 51.7% and 55.2% in ARM A and B with 1 and 6 discontinuations due to toxicity in ARM A and B, respectively. Health-related QoL was maintained (C30 functional scales & global health status remained stable pre-progression) and potentially improved (sustained improvement in role functioning) with nal-IRI/5-FU/folinic acid, but not docetaxel (all C30 functional scales & global health status worsened between baseline and week 18, and treatment-related symptoms also worsened in GINET21). Translational analysis is on-going.Conclusion: nal-IRI/5-FU warrants further evaluation in pts with PD-EP-NEC, with the results highlighting that conduct of randomised trials in this disease group of unmet need is possible and safe. ARM A (N=27) nal-IRI/5-FU, ARM B (N=29) Docetaxel6 mo PFS rate (%) 29.6 (lower 95% CI 15.68), 13.8 (lower 95% CI 4.85)ORR (%) 11.1 (95% CI 2.4-29.2), 10.3 (95% CI 2.2-27.4)Median PFS (mo) 3 (95% CI 2-6), 2 (95% CI 2-2)Median OS (mo) 6 (95% CI 3-10), 6 (95% CI 3-9)

KW - Second-line

KW - chemotherapy

KW - extra-pulmonary

KW - Neuroendocrine carcinoma

M3 - Abstract

T2 - ASCO GI 2023

Y2 - 19 January 2023 through 21 January 2023

ER -

Mcnamara M, Swain J, Craig Z, Sharma R, Faluyi O, Wadsley J et al.. NET-02 final results: A randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (PD-EP-NEC).. 2023. Abstract from ASCO GI 2023, San Francisco, United States.