Non-small cell lung cancer, RET-positive
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| Page editor | Section editor | ||
|---|---|---|---|
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Eric K. Singhi, MD MD Anderson Cancer Center Houston, TX, USA |
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Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN, USA |
Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.
7 regimens on this page
7 variants on this page
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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 PubMed
ESMO
- 2023: Hendriks et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
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 | Inferior PFS |
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 contains dosing details in manuscript PubMed NCT04194944
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 | Inferior PFS |
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 contains dosing details in manuscript PubMed NCT04194944
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 | Inferior PFS |
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 contains dosing details in manuscript PubMed NCT04194944
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 | Inferior PFS |
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 contains dosing details in manuscript PubMed NCT04194944
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 & Pemetrexed 1b. Carboplatin, Pemetrexed, Pembrolizumab 1c. Cisplatin & Pemetrexed 1d. Cisplatin, Pemetrexed, Pembrolizumab |
Superior PFS (primary endpoint) Median PFS: 24.8 vs 11.2 mo (HR 0.46, 95% CI 0.31-0.70) |
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 contains dosing details in manuscript PubMed NCT04194944
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
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 PubMed 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 PubMed
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 PubMed 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 PubMed
- 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 PubMed