STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP)
Por:
de Lima, VCC, Corassa, M, Saldanha, E, Freitas, H, Arrieta, O, Raez, L, Samtani, S, Ramos, M, Rojas, C, Burotto, M, Chamorro, DF, Recondo, G, Ruiz-Patino, A, Mas, L, Zatarain-Barron, L, Mejia, S, Minata, JN, Martin, C, Blaquier, JB, Guerrero, RM, Aliaga-Macha, C, Carracedo, C, Ordonez-Reyes, C, Garcia-Robledo, JE, Corrales, L, Sotelo, C, Ricaurte, L, Santoyo, N, Cuello, M, Jaller, E, Rodriguez, J, Archila, P, Bermudez, M, Gamez, T, Russo, A, Viola, L, Malapelle, U, Perez, DD, Rolfo, C, Rosell, R and Cardona, AF
Publicada:
1 ago 2022
Resumen:
Background: Mutations in STK11 (STK11(Mut)) and, frequently co-occurring, KEAP1 mutations (KEAP1(Mut)) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics. Methods: This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients' tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11(Wt)/KEAP1(Wt) population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B). Results: Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRAS(Mut) + STK11(Mut), KRAS(Mut) + STK11(Mut) + KEAP1(Mut), STK11(Mut) + KEAP1(Mut), and KRAS(Mut) + KEAP1(Mut), respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRAS(Wt) (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRAS(Mut) cases (p = 0.047). Tumors with KRAS(Mut) + KEAP1(Mut) had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3-5.4), slightly longer in those with KEAP1(mut) 6.1 months versus STK11(Mut) 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 >= 50% (30.9 months), and different from those with PD-L1 1-49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11(Mut) 14.2 months versus STK11(Wt) 27.0 months (p = 0.0001)] or KEAP1 [KEAP1(Mut) 12.0 months versus KEAP1(Wt) 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS. Conclusions: This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS.
Filiaciones:
de Lima, VCC:
AC Camargo Canc Ctr, Thorac Oncol Unit, Sao Paulo, Brazil
Corassa, M:
AC Camargo Canc Ctr, Thorac Oncol Unit, Sao Paulo, Brazil
Saldanha, E:
AC Camargo Canc Ctr, Thorac Oncol Unit, Sao Paulo, Brazil
Freitas, H:
AC Camargo Canc Ctr, Thorac Oncol Unit, Sao Paulo, Brazil
Arrieta, O:
Natl Canc Inst INCan, Thorac Oncol Unit, Mexico City, Mexico
Raez, L:
Mem Hlth Care Syst, Mem Canc Inst, Thorac Oncol Dept, Miami, FL USA
Samtani, S:
Bradford Hill Clin Res Ctr, Med Oncol Dept, Santiago, Chile
Ramos, M:
Natl Canc Inst INCan, Thorac Oncol Unit, Mexico City, Mexico
Rojas, C:
Bradford Hill Clin Res Ctr, Med Oncol Dept, Santiago, Chile
Burotto, M:
Bradford Hill Clin Res Ctr, Med Oncol Dept, Santiago, Chile
Chamorro, DF:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Recondo, G:
Ctr Educ Med Invest Clin CEMIC, Thorac Oncol Unit, Buenos Aires, Argentina
Ruiz-Patino, A:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Mas, L:
Inst Nacl Enfermedades Neoplas INEN, Med Oncol Dept, Lima, Peru
Zatarain-Barron, L:
Natl Canc Inst INCan, Thorac Oncol Unit, Mexico City, Mexico
Mejia, S:
Clin Amer AUNA, Inst Cancerol, Clin Oncol Dept, Medellin, Colombia
Minata, JN:
Hosp Italiano Buenos Aires, Clin Oncol Dept, Buenos Aires, Argentina
Martin, C:
Inst Alexander Fleming, Thorac Oncol Unit, Buenos Aires, Argentina
Blaquier, JB:
Ctr Educ Med Invest Clin CEMIC, Thorac Oncol Unit, Buenos Aires, Argentina
Guerrero, RM:
Ctr Oncol Aliada, Clin Oncol Dept, Lima, Peru
Aliaga-Macha, C:
Ctr Oncol Aliada, Clin Oncol Dept, Lima, Peru
Carracedo, C:
Ctr Oncol Aliada, Clin Oncol Dept, Lima, Peru
Ordonez-Reyes, C:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Garcia-Robledo, JE:
Mayo Clin, Div Hematol Oncol, Scottsdale, AZ USA
Corrales, L:
Ctr Invest & Manejo Canc CIMCA, Thorac Oncol Unit, San Jose, Costa Rica
Sotelo, C:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Ricaurte, L:
Mayo Clin, Pathol Dept, Rochester, MN USA
Santoyo, N:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Cuello, M:
Univ Republ UdeLAR, Hosp Clin, Med Oncol Dept, Montevideo, Uruguay
Jaller, E:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Rodriguez, J:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Archila, P:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Bermudez, M:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Gamez, T:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Russo, A:
Azienda Osped Papardo, Med Oncol Dept, Messina, Sicilia, Italy
Viola, L:
Fdn Neumol Colombiana, Thorac Oncol Unit, Bogota, Colombia
Malapelle, U:
Univ Feder II Naples, Dept Publ Hlth, Predict Mol Pathol Lab, Naples, Italy
Perez, DD:
Mt Sinai Hlth Syst, Tisch Canc Inst, Icahn Sch Med, Ctr Thorac Oncol, One Gustave Levy Pl, Mt Sinai, NY USA
Rolfo, C:
Mt Sinai Hlth Syst, Tisch Canc Inst, Icahn Sch Med, Ctr Thorac Oncol, One Gustave Levy Pl, Mt Sinai, NY USA
:
Dexeus Univ Inst, Germans Trias i Pujol Res Inst IGTP, Dr Rosell Oncol Inst IOR Quiron, Canc Biol & Precis Med Program, Barcelona, Spain
Cardona, AF:
Fdn Clin & Appl Canc Res FICMAC, Bogota, Colombia
Univ el Bosque, Mol Oncol & Biol Syst Res Grp FOX G, Bogota, Colombia
Luis Carlos Sarmiento Angulo Canc Treatment & Res, Direct Res Sci & Educ, Bogota, Colombia
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