Non-small cell lung cancer, RET-positive

Back to Top
Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.
There are several related dedicated pages:
*Histology-specific:
**NSCLC, Nonsquamous
**NSCLC, Squamous
*Site-specific:
**NSCLC, CNS metastases
Last updated on 2024-07-23:7 regimens on this page
7 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ASCO==
*2022: Singh et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline EuroPMC
==ESMO==
*2024: Lee et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer EuroPMC
*2023: Hendriks et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Non-Small Cell Lung Cancer.
=Advanced or metastatic disease, first-line therapy=
==Carboplatin & Pemetrexed==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2023 (LIBRETTO-431)	2020-03 to 2022-08 	Phase 3 (C)	Selpercatinib	Shorter PFSMedian PFS: 11.2 vs 24.8 mo(HR 2.17, 95% CI 1.43-3.23)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 (maximum dose of 750 mg) IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
===References===
#LIBRETTO-431: Zhou C, Solomon B, Loong HH, Park K, Pérol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. Epub 2023 Oct 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04194944
##Subgroup analysis: Pérol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. Epub 2024 Jun 3. link to original article EuroPMC
==Carboplatin, Pemetrexed, Pembrolizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2023 (LIBRETTO-431)	2020-03 to 2022-08 	Phase 3 (C)	Selpercatinib	Shorter PFSMedian PFS: 11.2 vs 24.8 mo(HR 2.17, 95% CI 1.43-3.23)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 (maximum dose of 750 mg) IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
====Immunotherapy====
*Pembrolizumab (Keytruda) as follows:
**Cycles 1 to 35: 200 mg IV once on day 1
21-day cycles
===References===
#LIBRETTO-431: Zhou C, Solomon B, Loong HH, Park K, Pérol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. Epub 2023 Oct 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04194944
##Subgroup analysis: Pérol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. Epub 2024 Jun 3. link to original article EuroPMC
==Cisplatin & Pemetrexed==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2023 (LIBRETTO-431)	2020-03 to 2022-08 	Phase 3 (C)	Selpercatinib	Shorter PFSMedian PFS: 11.2 vs 24.8 mo(HR 2.17, 95% CI 1.43-3.23)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 4: 75 mg/m2 IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
===References===
#LIBRETTO-431: Zhou C, Solomon B, Loong HH, Park K, Pérol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. Epub 2023 Oct 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04194944
##Subgroup analysis: Pérol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. Epub 2024 Jun 3. link to original article EuroPMC
==Cisplatin, Pemetrexed, Pembrolizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2023 (LIBRETTO-431)	2020-03 to 2022-08 	Phase 3 (C)	Selpercatinib	Shorter PFSMedian PFS: 11.2 vs 24.8 mo(HR 2.17, 95% CI 1.43-3.23)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 4: 75 mg/m2 IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
====Immunotherapy====
*Pembrolizumab (Keytruda) as follows:
**Cycles 1 to 35: 200 mg IV once on day 1
21-day cycles
===References===
#LIBRETTO-431: Zhou C, Solomon B, Loong HH, Park K, Pérol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. Epub 2023 Oct 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04194944
##Subgroup analysis: Pérol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. Epub 2024 Jun 3. link to original article EuroPMC
==Selpercatinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2023 (LIBRETTO-431)	2020-03 to 2022-08 	Phase 3 (E-switch-ooc)	1a. Carboplatin & Pemetrexed1b. Carboplatin, Pemetrexed, Pembrolizumab1c. Cisplatin & Pemetrexed1d. Cisplatin, Pemetrexed, Pembrolizumab	Longer PFS (primary endpoint)Median PFS: 24.8 vs 11.2 mo(HR 0.46, 95% CI 0.31-0.70)
====Targeted therapy====
*Selpercatinib (Retevmo) 160 mg PO twice per day on days 1 to 21
21-day cycles
===References===
#LIBRETTO-431: Zhou C, Solomon B, Loong HH, Park K, Pérol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. Epub 2023 Oct 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04194944
##Subgroup analysis: Pérol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. Epub 2024 Jun 3. link to original article EuroPMC
=Advanced or metastatic disease, all lines of therapy=
==Pralsetinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Gainor et al. 2021 (ARROWRET-NSCLC)	2017-2020 	Phase 1/2 (RT)
Note: this trial is denoted as ARROWRET-NSCLC to distinguish from other arms of this basket trial. This was the phase 2 dosing.
====Biomarker eligibility criteria====
*RET fusion positive
====Targeted therapy====
*Pralsetinib (Gavreto) 400 mg PO once per day
Continued indefinitely
===References===
#ARROWRET-NSCLC: Gainor JF, Curigliano G, Kim DW, Lee DH, Besse B, Baik CS, Doebele RC, Cassier PA, Lopes G, Tan DSW, Garralda E, Paz-Ares LG, Cho BC, Gadgeel SM, Thomas M, Liu SV, Taylor MH, Mansfield AS, Zhu VW, Clifford C, Zhang H, Palmer M, Green J, Turner CD, Subbiah V. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021 Jul;22(7):959-969. Epub 2021 Jun 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. link to original article EuroPMC NCT03037385
##Update: Griesinger F, Curigliano G, Thomas M, Subbiah V, Baik CS, Tan DSW, Lee DH, Misch D, Garralda E, Kim DW, van der Wekken AJ, Gainor JF, Paz-Ares L, Liu SV, Kalemkerian GP, Houvras Y, Bowles DW, Mansfield AS, Lin JJ, Smoljanovic V, Rahman A, Kong S, Zalutskaya A, Louie-Gao M, Boral AL, Mazières J. Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial. Ann Oncol. 2022 Nov;33(11):1168-1178. Epub 2022 Aug 13. link to original article EuroPMC
==Selpercatinib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Drilon et al. 2020 (LIBRETTO-001NSCLC)	2017-2018 	Phase 1/2 (RT)
====Biomarker eligibility criteria====
*RET fusion positive
====Targeted therapy====
*Selpercatinib (Retevmo) by the following weight-based criteria:
**Less than 50 kg: 120 mg PO twice per day
**50 kg or more: 160 mg PO twice per day
Continued indefinitely
===References===
# LIBRETTO-001NSCLC: Drilon A, Oxnard GR, Tan DSW, Loong HHF, Johnson M, Gainor J, McCoach CE, Gautschi O, Besse B, Cho BC, Peled N, Weiss J, Kim YJ, Ohe Y, Nishio M, Park K, Patel J, Seto T, Sakamoto T, Rosen E, Shah MH, Barlesi F, Cassier PA, Bazhenova L, De Braud F, Garralda E, Velcheti V, Satouchi M, Ohashi K, Pennell NA, Reckamp KL, Dy GK, Wolf J, Solomon B, Falchook G, Ebata K, Nguyen M, Nair B, Zhu EY, Yang L, Huang X, Olek E, Rothenberg SM, Goto K, Subbiah V. Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Aug 27;383(9):813-824. link to original article link to PMC article EuroPMC NCT03157128
##PRO analysis: Minchom A, Tan AC, Massarelli E, Subbiah V, Boni V, Robinson B, Wirth LJ, Hess LM, Jen MH, Kherani J, Olek E, McCoach CE. Patient-Reported Outcomes with Selpercatinib Among Patients with RET Fusion-Positive Non-Small Cell Lung Cancer in the Phase I/II LIBRETTO-001 Trial. Oncologist. 2022 Feb 3;27(1):22-29. link to original article link to PMC article EuroPMC
##Update: Drilon A, Subbiah V, Gautschi O, Tomasini P, de Braud F, Solomon BJ, Shao-Weng Tan D, Alonso G, Wolf J, Park K, Goto K, Soldatenkova V, Szymczak S, Barker SS, Puri T, Bence Lin A, Loong H, Besse B. Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. J Clin Oncol. 2023 Jan 10;41(2):385-394. Epub 2022 Sep 19. link to original article link to PMC article EuroPMC
Category:Non-small cell lung cancer regimens
Category:Biomarker-specific pages
Category:Non-small cell lung cancers