First-Line Lorlatinib or Crizotinib in Advanced

Adult Aged Aminopyridines Anaplastic Lymphoma Kinase / antagonists & inhibitors Antineoplastic Agents / adverse effects Carcinoma, Non-Small-Cell Lung / drug therapy Crizotinib / adverse effects Female Humans Hyperlipidemias / chemically induced Intention to Treat Analysis Lactams Lactams, Macrocyclic / adverse effects Lung Neoplasms / drug therapy Male Middle Aged Mutation Pyrazoles Survival Analysis

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
19 11 2020
Historique:
entrez: 18 11 2020
pubmed: 19 11 2020
medline: 15 12 2020
Statut: ppublish

Résumé

Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), has antitumor activity in previously treated patients with We conducted a global, randomized, phase 3 trial comparing lorlatinib with crizotinib in 296 patients with advanced The percentage of patients who were alive without disease progression at 12 months was 78% (95% confidence interval [CI], 70 to 84) in the lorlatinib group and 39% (95% CI, 30 to 48) in the crizotinib group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.19 to 0.41; P<0.001). An objective response occurred in 76% (95% CI, 68 to 83) of the patients in the lorlatinib group and 58% (95% CI, 49 to 66) of those in the crizotinib group; among those with measurable brain metastases, 82% (95% CI, 57 to 96) and 23% (95% CI, 5 to 54), respectively, had an intracranial response, and 71% of the patients who received lorlatinib had an intracranial complete response. The most common adverse events with lorlatinib were hyperlipidemia, edema, increased weight, peripheral neuropathy, and cognitive effects. Lorlatinib was associated with more grade 3 or 4 adverse events (mainly altered lipid levels) than crizotinib (in 72% vs. 56%). Discontinuation of treatment because of adverse events occurred in 7% and 9% of the patients, respectively. In an interim analysis of results among patients with previously untreated advanced

Sections du résumé

BACKGROUND
Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), has antitumor activity in previously treated patients with
METHODS
We conducted a global, randomized, phase 3 trial comparing lorlatinib with crizotinib in 296 patients with advanced
RESULTS
The percentage of patients who were alive without disease progression at 12 months was 78% (95% confidence interval [CI], 70 to 84) in the lorlatinib group and 39% (95% CI, 30 to 48) in the crizotinib group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.19 to 0.41; P<0.001). An objective response occurred in 76% (95% CI, 68 to 83) of the patients in the lorlatinib group and 58% (95% CI, 49 to 66) of those in the crizotinib group; among those with measurable brain metastases, 82% (95% CI, 57 to 96) and 23% (95% CI, 5 to 54), respectively, had an intracranial response, and 71% of the patients who received lorlatinib had an intracranial complete response. The most common adverse events with lorlatinib were hyperlipidemia, edema, increased weight, peripheral neuropathy, and cognitive effects. Lorlatinib was associated with more grade 3 or 4 adverse events (mainly altered lipid levels) than crizotinib (in 72% vs. 56%). Discontinuation of treatment because of adverse events occurred in 7% and 9% of the patients, respectively.
CONCLUSIONS
In an interim analysis of results among patients with previously untreated advanced

Identifiants

DOI: 10.1056/NEJMoa2027187 PMID: 33207094
pubmed: 33207094
doi: 10.1056/NEJMoa2027187
doi:

Substances chimiques

Aminopyridines 0
Antineoplastic Agents 0
Lactams 0
Lactams, Macrocyclic 0
Pyrazoles 0
Crizotinib 53AH36668S
ALK protein, human EC 2.7.10.1
Anaplastic Lymphoma Kinase EC 2.7.10.1
lorlatinib OSP71S83EU

Banques de données

ClinicalTrials.gov
['NCT03052608']

Types de publication

Clinical Trial, Phase III Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2018-2029

Subventions

Organisme : Pfizer
ID : N/A
Pays : International

Investigateurs

Susana Kahl (S)
Guillermo Streich (G)
Benjamin Solomon (B)
Jean-Luc Canon (JL)
Vera Hirsh (V)
Geoffrey Liu (G)
Ying Cheng (Y)
Yun Fan (Y)
Baohui Han (B)
Jianjin Huang (J)
Xiaoqing Liu (X)
Shun Lu (S)
Jun Zhao (J)
Jianying Zhou (J)
Qing Zhou (Q)
Vitezslav Kolek (V)
Milada Zemanova (M)
Benjamin Besse (B)
Helene Doubre (H)
Anne Madroszyk-Flandin (A)
Julien Mazieres (J)
Olivier Molinier (O)
Pascale Tomasini (P)
Remi Veillon (R)
Gerard Zalcman (G)
Helge Bischoff (H)
Christian Schulz (C)
Martin Wermke (M)
James Chung Man Ho (JCM)
Ka Chai Lee (KC)
Victor Ho-Fun Lee (VH)
Hari Goyal (H)
K Lakshmaiah (K)
Tushar Patil (T)
Alessandra Bearz (A)
Federico Cappuzzo (F)
Francesco Cognetti (F)
Diego Cortinovis (D)
Filippo de Marinis (F)
Luca Gianni (L)
Maria Rita Migliorino (MR)
Vincenzo Minotti (V)
Alessandro Morabito (A)
Francovito Piantedosi (F)
Hector Jose Soto Parra (HJ)
Luca Toschi (L)
Nicoletta Zilembo (N)
Keisuke Aoe (K)
Koichi Azuma (K)
Haruko Daga (H)
Yasushi Goto (Y)
Hidetoshi Hayashi (H)
Eiki Ichihara (E)
Terufumi Kato (T)
Toru Kumagai (T)
Masahiro Morise (M)
Makoto Nishio (M)
Naoyuki Nogami (N)
Hiroshi Nokihara (H)
Satoshi Oizumi (S)
Sugawara Shunichi (S)
Toshiaki Takahashi (T)
Hiroshi Tanaka (H)
Shunsuke Teraoka (S)
Byoung Chul Cho (BC)
Dong-Wan Kim (DW)
Sang-We Kim (SW)
Young Joo Min (YJ)
Byoung Yong Shim (BY)
Jorge Alatorre Alexander (JA)
Oscar Arrieta-Rodriguez (O)
Froylan Lopez-Lopez (F)
Anthonie Van Der Wekken (A)
Jacek Jassem (J)
Dariusz Kowalski (D)
Rodryg Ramlau (R)
Piotr Serwatowski (P)
Mikhail Dvorkin (M)
Konstantin Laktionov (K)
Fedor Moiseenko (F)
Konstantin Penkov (K)
Lynette Ngo (L)
Ross Soo (R)
Joaquim Bosch Barrera (J)
Manuel Domine Gomez (M)
Enriqueta Felip (E)
Maria Garcia Campelo (M)
Pilar Garrido Lopez (P)
Jose Luis Gonzalez Larriba (JL)
Maite Martinez Aguillo (M)
Ernest Nadal Alforja (E)
Mariano Provencio Pulla (M)
Noemi Reguart Aransay (N)
Gee-Chen Chang (GC)
Chao-Hua Chiu (CH)
Chia-Chi Lin (CC)
Meng-Chih Lin (MC)
Adnan Aydiner (A)
Shobhit Baijal (S)
Fiona Blackhall (F)
Kent Yip (K)
Christina Baik (C)
Maen Hussein (M)
Alice Shaw (A)
Benjamin J Solomon (BJ)
Alice T Shaw (AT)
Todd M Bauer (TM)
Tony Mok (T)

Commentaires et corrections

Type : CommentIn
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Informations de copyright

Copyright © 2020 Massachusetts Medical Society.

Auteurs

Alice T Shaw (AT)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Todd M Bauer (TM)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Filippo de Marinis (F)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Enriqueta Felip (E)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Yasushi Goto (Y)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Geoffrey Liu (G)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Julien Mazieres (J)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Dong-Wan Kim (DW)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Tony Mok (T)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Anna Polli (A)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Holger Thurm (H)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Anna M Calella (AM)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Gerson Peltz (G)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Benjamin J Solomon (BJ)

From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) - both in Boston; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) - both in Milan; Vall d'Hebron University Hospital and Institute of Oncology, International Oncology Bureau-Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Aminopyridines › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs à activité tyrosine kinase › Kinase du lymphome anaplasique › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire non à petites cellules › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Aminopyridines › Crizotinib › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles du métabolisme lipidique › Dyslipidémies › Hyperlipidémies › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques contrôlés comme sujet › Essais contrôlés randomisés comme sujet › Analyse en intention de traitement › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Lactames › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Composés polycycliques › Composés macrocycliques › Lactames macrocycliques › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Pyrazoles › First-Line Lorlatinib or Crizotinib in Advanced
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › First-Line Lorlatinib or Crizotinib in Advanced