The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis
Background: In untreated ALK-positive non-small cell lung cancer no randomized controlled trials (RCTs) are available directly comparing next-generation ALK-inhibitors. We conducted a sensitivity analysis using the likelihood of being helped or harmed (LHH). Methods: Phase III trials comparing ALK-i...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Cancer Treatment and Research Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468294224000546 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850058163771932672 |
|---|---|
| author | Luca Mastrantoni Giulia Giordano Emanuele Vita Guido Horn Jacopo Russo Armando Orlandi Gennaro Daniele Diana Giannarelli Giampaolo Tortora Emilio Bria |
| author_facet | Luca Mastrantoni Giulia Giordano Emanuele Vita Guido Horn Jacopo Russo Armando Orlandi Gennaro Daniele Diana Giannarelli Giampaolo Tortora Emilio Bria |
| author_sort | Luca Mastrantoni |
| collection | DOAJ |
| description | Background: In untreated ALK-positive non-small cell lung cancer no randomized controlled trials (RCTs) are available directly comparing next-generation ALK-inhibitors. We conducted a sensitivity analysis using the likelihood of being helped or harmed (LHH). Methods: Phase III trials comparing ALK-inhibitors to crizotinib were included. Efficacy outcomes were progression-free survival (PFS), objective response rate (ORR), PFS in patients with brain metastases and intracranial ORR. Safety outcomes were grade 3–4 adverse events (AEs), dose reductions and discontinuations. Results: Six RCTs (1524 patients) were included. Lorlatinib and brigatinib had the lowest NNT for intracranial outcomes. Alectinib demonstrated favourable LHHs for grade 3–4 AEs, dose reductions and discontinuations. Brigatinib LHHs were low for common AEs, mainly laboratory anomalies and hypertension. Ensartinib showed mainly skin toxicity. Lorlatinib LHHs were low for specific grade 3–4 AEs, mainly metabolic alterations. Conclusions: The four ALK-inhibitors exhibited favourable risk-benefit ratios. Lorlatinib showed the lowest NNT for systemic efficacy and, alongside with Brigatinib, lower NNTs for intracranial efficacy. Alectinib exhibited higher LHHs for AEs. Registration: PROSPERO registration number: CRD42023389101. |
| format | Article |
| id | doaj-art-027ba545a3d04abb89e195068dc14876 |
| institution | DOAJ |
| issn | 2468-2942 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cancer Treatment and Research Communications |
| spelling | doaj-art-027ba545a3d04abb89e195068dc148762025-08-20T02:51:14ZengElsevierCancer Treatment and Research Communications2468-29422024-01-014110084210.1016/j.ctarc.2024.100842The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysisLuca Mastrantoni0Giulia Giordano1Emanuele Vita2Guido Horn3Jacopo Russo4Armando Orlandi5Gennaro Daniele6Diana Giannarelli7Giampaolo Tortora8Emilio Bria9Medical Oncology, Università Cattolica del Sacro Cuore, Rome, ItalyDepartment of Aging, Orthopedics and Reumatological Sciences, Università Cattolica del Sacro Cuore, Rome, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, Rome, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, Rome, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, ItalyUOC Phase I, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyBiostatistic, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy; Medical Oncology Unit, Ospedale Isola Tiberina, Gemelli Isola, Rome, Italy; Corresponding author at: Medical Oncology, Università Cattolica del Sacro Cuore. Largo Francesco Vito 1, 00168, Roma, RM, Rome, Italy.Background: In untreated ALK-positive non-small cell lung cancer no randomized controlled trials (RCTs) are available directly comparing next-generation ALK-inhibitors. We conducted a sensitivity analysis using the likelihood of being helped or harmed (LHH). Methods: Phase III trials comparing ALK-inhibitors to crizotinib were included. Efficacy outcomes were progression-free survival (PFS), objective response rate (ORR), PFS in patients with brain metastases and intracranial ORR. Safety outcomes were grade 3–4 adverse events (AEs), dose reductions and discontinuations. Results: Six RCTs (1524 patients) were included. Lorlatinib and brigatinib had the lowest NNT for intracranial outcomes. Alectinib demonstrated favourable LHHs for grade 3–4 AEs, dose reductions and discontinuations. Brigatinib LHHs were low for common AEs, mainly laboratory anomalies and hypertension. Ensartinib showed mainly skin toxicity. Lorlatinib LHHs were low for specific grade 3–4 AEs, mainly metabolic alterations. Conclusions: The four ALK-inhibitors exhibited favourable risk-benefit ratios. Lorlatinib showed the lowest NNT for systemic efficacy and, alongside with Brigatinib, lower NNTs for intracranial efficacy. Alectinib exhibited higher LHHs for AEs. Registration: PROSPERO registration number: CRD42023389101.http://www.sciencedirect.com/science/article/pii/S2468294224000546ALK-inhibitorsAlectinibLorlatinibBrigatinibEnsartinibLHH |
| spellingShingle | Luca Mastrantoni Giulia Giordano Emanuele Vita Guido Horn Jacopo Russo Armando Orlandi Gennaro Daniele Diana Giannarelli Giampaolo Tortora Emilio Bria The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis Cancer Treatment and Research Communications ALK-inhibitors Alectinib Lorlatinib Brigatinib Ensartinib LHH |
| title | The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis |
| title_full | The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis |
| title_fullStr | The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis |
| title_full_unstemmed | The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis |
| title_short | The likelihood of being helped or harmed as a patient-centred tool to assess ALK-Inhibitors clinical impact and safety in ALK-addicted non-small cell lung cancer: A systematic review and sensitivity-analysis |
| title_sort | likelihood of being helped or harmed as a patient centred tool to assess alk inhibitors clinical impact and safety in alk addicted non small cell lung cancer a systematic review and sensitivity analysis |
| topic | ALK-inhibitors Alectinib Lorlatinib Brigatinib Ensartinib LHH |
| url | http://www.sciencedirect.com/science/article/pii/S2468294224000546 |
| work_keys_str_mv | AT lucamastrantoni thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT giuliagiordano thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT emanuelevita thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT guidohorn thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT jacoporusso thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT armandoorlandi thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT gennarodaniele thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT dianagiannarelli thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT giampaolotortora thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT emiliobria thelikelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT lucamastrantoni likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT giuliagiordano likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT emanuelevita likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT guidohorn likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT jacoporusso likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT armandoorlandi likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT gennarodaniele likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT dianagiannarelli likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT giampaolotortora likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis AT emiliobria likelihoodofbeinghelpedorharmedasapatientcentredtooltoassessalkinhibitorsclinicalimpactandsafetyinalkaddictednonsmallcelllungcancerasystematicreviewandsensitivityanalysis |