Skip to main content
Top
Published in: BMC Cancer 1/2021

01-12-2021 | NSCLC | Research article

Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung cancer patients: a retrospective multicenter study

Authors: Kazutaka Hosoya, Daichi Fujimoto, Takeshi Morimoto, Toru Kumagai, Akihiro Tamiya, Yoshihiko Taniguchi, Toshihide Yokoyama, Tadashi Ishida, Hirotaka Matsumoto, Katsuya Hirano, Ryota Kominami, Keisuke Tomii, Hidekazu Suzuki, Tomonori Hirashima, Satoshi Tanaka, Junji Uchida, Mitsunori Morita, Masaki Kanazu, Masahide Mori, Kenji Nagata, Ikue Fukuda, Motohiro Tamiya

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

Background

Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved.

Methods

We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions.

Results

Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR.

Conclusions

Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.
Appendix
Available only for authorised users
Literature
5.
go back to reference Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G, Adamchuk G, Ahn MJ, Alexandru A, Altundag O, Alyasova A, Andrusenko O, Aoe K, Araujo A, Aren O, Arrieta Rodriguez O, Ativitavas T, Avendano O, Barata F, Barrios CH, Beato C, Bergstrom P, Betticher D, Bolotina L, Bondarenko I, Botha M, Buddu S, Caglevic C, Cardona A, Castro G Jr, Castro H, Cay Senler F, Cerny CAS, Cesas A, Chan GC, Chang J, Chen G, Chen X, Cheng S, Cheng Y, Cherciu N, Chiu CH, Cho BC, Cicenas S, Ciurescu D, Cohen G, Costa MA, Danchaivijitr P, de Angelis F, de Azevedo SJ, Dediu M, Deliverski T, de Marchi PRM, de The Bustamante Valles F, Ding Z, Doganov B, Dreosti L, Duarte R, Edusma-Dy R, Emelyanov S, Erman M, Fan Y, Fein L, Feng J, Fenton D, Fernandes G, Ferreira C, Franke FA, Freitas H, Fujisaka Y, Galindo H, Galvez C, Ganea D, Gil N, Girotto G, Goker E, Goksel T, Gomez Aubin G, Gomez Wolff L, Griph H, Gumus M, Hall J, Hart G, Havel L, He J, He Y, Hernandez Hernandez C, Hespanhol V, Hirashima T, Ho CMJ, Horiike A, Hosomi Y, Hotta K, Hou M, How SH, Hsia TC, Hu Y, Ichiki M, Imamura F, Ivashchuk O, Iwamoto Y, Jaal J, Jassem J, Jordaan C, Juergens RA, Kaen D, Kalinka-Warzocha E, Karaseva N, Karaszewska B, Kazarnowicz A, Kasahara K, Katakami N, Kato T, Kawaguchi T, Kim JH, Kishi K, Kolek V, Koleva M, Kolman P, Koubkova L, Kowalyszyn R, Kowalski D, Koynov K, Ksienski D, Kubota K, Kudaba I, Kurata T, Kuusk G, Kuzina L, Laczo I, Ladrera GEI, Laktionov K, Landers G, Lazarev S, Lerzo G, Lesniewski Kmak K, Li W, Liam CK, Lifirenko I, Lipatov O, Liu X, Liu Z, Lo SH, Lopes V, Lopez K, Lu S, Martinengo G, Mas L, Matrosova M, Micheva R, Milanova Z, Miron L, Mok T, Molina M, Murakami S, Nakahara Y, Nguyen TQ, Nishimura T, Ochsenbein A, Ohira T, Ohman R, Ong CK, Ostoros G, Ouyang X, Ovchinnikova E, Ozyilkan O, Petruzelka L, Pham XD, Picon P, Piko B, Poltoratsky A, Ponomarova O, Popelkova P, Purkalne G, Qin S, Ramlau R, Rappaport B, Rey F, Richardet E, Roubec J, Ruff P, Rusyn A, Saka H, Salas J, Sandoval M, Santos L, Sawa T, Seetalarom K, Seker M, Seki N, Seolwane F, Shepherd L, Shevnya S, Shimada AK, Shparyk Y, Sinielnikov I, Sirbu D, Smaletz O, Soares JPH, Sookprasert A, Speranza G, Srimuninnimit V, Sriuranpong V, Stara Z, Su WC, Sugawara S, Szpak W, Takahashi K, Takigawa N, Tanaka H, Tan Chun Bing J, Tang Q, Taranov P, Tejada H, Tho LM, Torii Y, Trukhyn D, Turdean M, Turna H, Ursol G, Vanasek J, Varela M, Vallejo M, Vera L, Victorino AP, Vlasek T, Vynnychenko I, Wang B, Wang J, Wang K, Wu Y, Yamada K, Yang CH, Yokoyama T, Yokoyama T, Yoshioka H, Yumuk F, Zambrano A, Zarba JJ, Zarubenkov O, Zemaitis M, Zhang L, Zhang L, Zhang X, Zhao J, Zhou C, Zhou J, Zhou Q, Zippelius A. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819–30. https://doi.org/10.1016/S0140-6736(18)32409-7.CrossRefPubMed Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G, Adamchuk G, Ahn MJ, Alexandru A, Altundag O, Alyasova A, Andrusenko O, Aoe K, Araujo A, Aren O, Arrieta Rodriguez O, Ativitavas T, Avendano O, Barata F, Barrios CH, Beato C, Bergstrom P, Betticher D, Bolotina L, Bondarenko I, Botha M, Buddu S, Caglevic C, Cardona A, Castro G Jr, Castro H, Cay Senler F, Cerny CAS, Cesas A, Chan GC, Chang J, Chen G, Chen X, Cheng S, Cheng Y, Cherciu N, Chiu CH, Cho BC, Cicenas S, Ciurescu D, Cohen G, Costa MA, Danchaivijitr P, de Angelis F, de Azevedo SJ, Dediu M, Deliverski T, de Marchi PRM, de The Bustamante Valles F, Ding Z, Doganov B, Dreosti L, Duarte R, Edusma-Dy R, Emelyanov S, Erman M, Fan Y, Fein L, Feng J, Fenton D, Fernandes G, Ferreira C, Franke FA, Freitas H, Fujisaka Y, Galindo H, Galvez C, Ganea D, Gil N, Girotto G, Goker E, Goksel T, Gomez Aubin G, Gomez Wolff L, Griph H, Gumus M, Hall J, Hart G, Havel L, He J, He Y, Hernandez Hernandez C, Hespanhol V, Hirashima T, Ho CMJ, Horiike A, Hosomi Y, Hotta K, Hou M, How SH, Hsia TC, Hu Y, Ichiki M, Imamura F, Ivashchuk O, Iwamoto Y, Jaal J, Jassem J, Jordaan C, Juergens RA, Kaen D, Kalinka-Warzocha E, Karaseva N, Karaszewska B, Kazarnowicz A, Kasahara K, Katakami N, Kato T, Kawaguchi T, Kim JH, Kishi K, Kolek V, Koleva M, Kolman P, Koubkova L, Kowalyszyn R, Kowalski D, Koynov K, Ksienski D, Kubota K, Kudaba I, Kurata T, Kuusk G, Kuzina L, Laczo I, Ladrera GEI, Laktionov K, Landers G, Lazarev S, Lerzo G, Lesniewski Kmak K, Li W, Liam CK, Lifirenko I, Lipatov O, Liu X, Liu Z, Lo SH, Lopes V, Lopez K, Lu S, Martinengo G, Mas L, Matrosova M, Micheva R, Milanova Z, Miron L, Mok T, Molina M, Murakami S, Nakahara Y, Nguyen TQ, Nishimura T, Ochsenbein A, Ohira T, Ohman R, Ong CK, Ostoros G, Ouyang X, Ovchinnikova E, Ozyilkan O, Petruzelka L, Pham XD, Picon P, Piko B, Poltoratsky A, Ponomarova O, Popelkova P, Purkalne G, Qin S, Ramlau R, Rappaport B, Rey F, Richardet E, Roubec J, Ruff P, Rusyn A, Saka H, Salas J, Sandoval M, Santos L, Sawa T, Seetalarom K, Seker M, Seki N, Seolwane F, Shepherd L, Shevnya S, Shimada AK, Shparyk Y, Sinielnikov I, Sirbu D, Smaletz O, Soares JPH, Sookprasert A, Speranza G, Srimuninnimit V, Sriuranpong V, Stara Z, Su WC, Sugawara S, Szpak W, Takahashi K, Takigawa N, Tanaka H, Tan Chun Bing J, Tang Q, Taranov P, Tejada H, Tho LM, Torii Y, Trukhyn D, Turdean M, Turna H, Ursol G, Vanasek J, Varela M, Vallejo M, Vera L, Victorino AP, Vlasek T, Vynnychenko I, Wang B, Wang J, Wang K, Wu Y, Yamada K, Yang CH, Yokoyama T, Yokoyama T, Yoshioka H, Yumuk F, Zambrano A, Zarba JJ, Zarubenkov O, Zemaitis M, Zhang L, Zhang L, Zhang X, Zhao J, Zhou C, Zhou J, Zhou Q, Zippelius A. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819–30. https://​doi.​org/​10.​1016/​S0140-6736(18)32409-7.CrossRefPubMed
6.
go back to reference Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung Cancer. N Engl J Med. 2015;373(17):1627–39. https://doi.org/10.1056/NEJMoa1507643.CrossRefPubMedPubMedCentral Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung Cancer. N Engl J Med. 2015;373(17):1627–39. https://​doi.​org/​10.​1056/​NEJMoa1507643.CrossRefPubMedPubMedCentral
9.
go back to reference Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, de Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR, OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65. https://doi.org/10.1016/S0140-6736(16)32517-X.CrossRefPubMed Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, de Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR, OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65. https://​doi.​org/​10.​1016/​S0140-6736(16)32517-X.CrossRefPubMed
10.
go back to reference Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhäeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crinò L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. Nivolumab versus Docetaxel in previously treated patients with advanced non-small-cell lung Cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017;35(35):3924–33. https://doi.org/10.1200/JCO.2017.74.3062.CrossRefPubMedPubMedCentral Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhäeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crinò L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. Nivolumab versus Docetaxel in previously treated patients with advanced non-small-cell lung Cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017;35(35):3924–33. https://​doi.​org/​10.​1200/​JCO.​2017.​74.​3062.CrossRefPubMedPubMedCentral
14.
go back to reference Laurie SA, Banerji S, Blais N, Brule S, Cheema PK, Cheung P, Daaboul N, Hao D, Hirsh V, Juergens R, et al. Canadian consensus: oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer. Curr Oncol (Toronto, Ont). 2019;26(1):e81–93.CrossRef Laurie SA, Banerji S, Blais N, Brule S, Cheema PK, Cheung P, Daaboul N, Hao D, Hirsh V, Juergens R, et al. Canadian consensus: oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer. Curr Oncol (Toronto, Ont). 2019;26(1):e81–93.CrossRef
15.
go back to reference Iyengar P, Kavanagh BD, Wardak Z, Smith I, Ahn C, Gerber DE, Dowell J, Hughes R, Abdulrahman R, Camidge DR, Gaspar LE, Doebele RC, Bunn PA, Choy H, Timmerman R. Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer. J Clin Oncol. 2014;32(34):3824–30. https://doi.org/10.1200/JCO.2014.56.7412.CrossRefPubMed Iyengar P, Kavanagh BD, Wardak Z, Smith I, Ahn C, Gerber DE, Dowell J, Hughes R, Abdulrahman R, Camidge DR, Gaspar LE, Doebele RC, Bunn PA, Choy H, Timmerman R. Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer. J Clin Oncol. 2014;32(34):3824–30. https://​doi.​org/​10.​1200/​JCO.​2014.​56.​7412.CrossRefPubMed
18.
19.
go back to reference Yu HA, Sima CS, Huang J, Solomon SB, Rimner A, Paik P, Pietanza MC, Azzoli CG, Rizvi NA, Krug LM, Miller VA, Kris MG, Riely GJ. Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013;8(3):346–51. https://doi.org/10.1097/JTO.0b013e31827e1f83.CrossRefPubMedPubMedCentral Yu HA, Sima CS, Huang J, Solomon SB, Rimner A, Paik P, Pietanza MC, Azzoli CG, Rizvi NA, Krug LM, Miller VA, Kris MG, Riely GJ. Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013;8(3):346–51. https://​doi.​org/​10.​1097/​JTO.​0b013e31827e1f83​.CrossRefPubMedPubMedCentral
20.
go back to reference Qian J, Nie W, Lu J, Zhang L, Zhang Y, Zhang B, Wang S, Hu M, Xu J, Lou Y, Dong Y, Niu Y, Yan B, Zhong R, Zhang W, Chu T, Zhong H, Han B. Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: an ancillary analysis of the POPLAR and OAK studies. Int J Cancer. 2020;146(11):3124–33. https://doi.org/10.1002/ijc.32717.CrossRefPubMed Qian J, Nie W, Lu J, Zhang L, Zhang Y, Zhang B, Wang S, Hu M, Xu J, Lou Y, Dong Y, Niu Y, Yan B, Zhong R, Zhang W, Chu T, Zhong H, Han B. Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: an ancillary analysis of the POPLAR and OAK studies. Int J Cancer. 2020;146(11):3124–33. https://​doi.​org/​10.​1002/​ijc.​32717.CrossRefPubMed
23.
go back to reference Teraoka S, Fujimoto D, Morimoto T, Kawachi H, Ito M, Sato Y, Nagata K, Nakagawa A, Otsuka K, Uehara K, Imai Y, Ishida K, Fukuoka J, Tomii K. Early immune-related adverse events and association with outcome in advanced non-small cell lung Cancer patients treated with Nivolumab: a prospective cohort study. J Thorac Oncol. 2017;12(12):1798–805. https://doi.org/10.1016/j.jtho.2017.08.022.CrossRefPubMed Teraoka S, Fujimoto D, Morimoto T, Kawachi H, Ito M, Sato Y, Nagata K, Nakagawa A, Otsuka K, Uehara K, Imai Y, Ishida K, Fukuoka J, Tomii K. Early immune-related adverse events and association with outcome in advanced non-small cell lung Cancer patients treated with Nivolumab: a prospective cohort study. J Thorac Oncol. 2017;12(12):1798–805. https://​doi.​org/​10.​1016/​j.​jtho.​2017.​08.​022.CrossRefPubMed
24.
go back to reference Hosoya K, Fujimoto D, Morimoto T, Kumagai T, Tamiya A, Taniguchi Y, Yokoyama T, Ishida T, Hirano K, Matsumoto H, Kominami R, Tomii K, Suzuki H, Hirashima T, Uchida J, Morita M, Kanazu M, Sawa N, Makio T, Hara S, Tamiya M. Association between early immune-related adverse events and clinical outcomes in patients with non-small cell lung Cancer treated with immune checkpoint inhibitors. Clin Lung Cancer. 2020;21(4):e315–28. https://doi.org/10.1016/j.cllc.2020.01.003.CrossRefPubMed Hosoya K, Fujimoto D, Morimoto T, Kumagai T, Tamiya A, Taniguchi Y, Yokoyama T, Ishida T, Hirano K, Matsumoto H, Kominami R, Tomii K, Suzuki H, Hirashima T, Uchida J, Morita M, Kanazu M, Sawa N, Makio T, Hara S, Tamiya M. Association between early immune-related adverse events and clinical outcomes in patients with non-small cell lung Cancer treated with immune checkpoint inhibitors. Clin Lung Cancer. 2020;21(4):e315–28. https://​doi.​org/​10.​1016/​j.​cllc.​2020.​01.​003.CrossRefPubMed
25.
go back to reference Fujimoto D, Yoshioka H, Kataoka Y, Morimoto T, Kim YH, Tomii K, Ishida T, Hirabayashi M, Hara S, Ishitoko M, Fukuda Y, Hwang MH, Sakai N, Fukui M, Nakaji H, Morita M, Mio T, Yasuda T, Sugita T, Hirai T. Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: a multicenter retrospective cohort study. Lung Cancer. 2018;119:14–20. https://doi.org/10.1016/j.lungcan.2018.02.017.CrossRefPubMed Fujimoto D, Yoshioka H, Kataoka Y, Morimoto T, Kim YH, Tomii K, Ishida T, Hirabayashi M, Hara S, Ishitoko M, Fukuda Y, Hwang MH, Sakai N, Fukui M, Nakaji H, Morita M, Mio T, Yasuda T, Sugita T, Hirai T. Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: a multicenter retrospective cohort study. Lung Cancer. 2018;119:14–20. https://​doi.​org/​10.​1016/​j.​lungcan.​2018.​02.​017.CrossRefPubMed
33.
go back to reference Dovedi SJ, Cheadle EJ, Popple AL, Poon E, Morrow M, Stewart R, Yusko EC, Sanders CM, Vignali M, Emerson RO, Robins HS, Wilkinson RW, Honeychurch J, Illidge TM. Fractionated radiation therapy stimulates antitumor immunity mediated by both resident and infiltrating polyclonal T-cell populations when combined with PD-1 blockade. Clin Cancer Res. 2017;23(18):5514–26. https://doi.org/10.1158/1078-0432.CCR-16-1673.CrossRefPubMed Dovedi SJ, Cheadle EJ, Popple AL, Poon E, Morrow M, Stewart R, Yusko EC, Sanders CM, Vignali M, Emerson RO, Robins HS, Wilkinson RW, Honeychurch J, Illidge TM. Fractionated radiation therapy stimulates antitumor immunity mediated by both resident and infiltrating polyclonal T-cell populations when combined with PD-1 blockade. Clin Cancer Res. 2017;23(18):5514–26. https://​doi.​org/​10.​1158/​1078-0432.​CCR-16-1673.CrossRefPubMed
34.
go back to reference Theelen W, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts J, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, et al. Effect of Pembrolizumab after stereotactic body radiotherapy vs Pembrolizumab alone on tumor response in patients with advanced non-small cell lung Cancer: results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA Oncol. 2019;5(9):1276. https://doi.org/10.1001/jamaoncol.2019.1478.CrossRefPubMedPubMedCentral Theelen W, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts J, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, et al. Effect of Pembrolizumab after stereotactic body radiotherapy vs Pembrolizumab alone on tumor response in patients with advanced non-small cell lung Cancer: results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA Oncol. 2019;5(9):1276. https://​doi.​org/​10.​1001/​jamaoncol.​2019.​1478.CrossRefPubMedPubMedCentral
35.
go back to reference Campbell AM, Cai WL, Burkhardt D, Gettinger SN, Goldberg SB, Amodio M, Kaech S, Krishnaswamy S, Decker RH. Final results of a phase II prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent Pembrolizumab in patients with metastatic non-small cell lung Cancer (NSCLC). Int J Radiat Oncol. 2019;105(1):S36–7. https://doi.org/10.1016/j.ijrobp.2019.06.453.CrossRef Campbell AM, Cai WL, Burkhardt D, Gettinger SN, Goldberg SB, Amodio M, Kaech S, Krishnaswamy S, Decker RH. Final results of a phase II prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent Pembrolizumab in patients with metastatic non-small cell lung Cancer (NSCLC). Int J Radiat Oncol. 2019;105(1):S36–7. https://​doi.​org/​10.​1016/​j.​ijrobp.​2019.​06.​453.CrossRef
40.
go back to reference Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, Zhang T, Adleff V, Phallen J, Wali N, Hruban C, Guthrie VB, Rodgers K, Naidoo J, Kang H, Sharfman W, Georgiades C, Verde F, Illei P, Li QK, Gabrielson E, Brock MV, Zahnow CA, Baylin SB, Scharpf RB, Brahmer JR, Karchin R, Pardoll DM, Velculescu VE. Evolution of Neoantigen landscape during immune checkpoint blockade in non-small cell lung Cancer. Cancer discovery. 2017;7(3):264–76. https://doi.org/10.1158/2159-8290.CD-16-0828.CrossRefPubMed Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, Zhang T, Adleff V, Phallen J, Wali N, Hruban C, Guthrie VB, Rodgers K, Naidoo J, Kang H, Sharfman W, Georgiades C, Verde F, Illei P, Li QK, Gabrielson E, Brock MV, Zahnow CA, Baylin SB, Scharpf RB, Brahmer JR, Karchin R, Pardoll DM, Velculescu VE. Evolution of Neoantigen landscape during immune checkpoint blockade in non-small cell lung Cancer. Cancer discovery. 2017;7(3):264–76. https://​doi.​org/​10.​1158/​2159-8290.​CD-16-0828.CrossRefPubMed
41.
go back to reference Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA class I antigen processing and presentation as a mechanism of acquired resistance to immune checkpoint inhibitors in lung Cancer. Cancer discovery. 2017;7(12):1420–35. https://doi.org/10.1158/2159-8290.CD-17-0593.CrossRefPubMedPubMedCentral Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA class I antigen processing and presentation as a mechanism of acquired resistance to immune checkpoint inhibitors in lung Cancer. Cancer discovery. 2017;7(12):1420–35. https://​doi.​org/​10.​1158/​2159-8290.​CD-17-0593.CrossRefPubMedPubMedCentral
42.
go back to reference Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, Saco J, Homet Moreno B, Mezzadra R, Chmielowski B, Ruchalski K, Shintaku IP, Sanchez PJ, Puig-Saus C, Cherry G, Seja E, Kong X, Pang J, Berent-Maoz B, Comin-Anduix B, Graeber TG, Tumeh PC, Schumacher TNM, Lo RS, Ribas A. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819–29. https://doi.org/10.1056/NEJMoa1604958.CrossRefPubMedPubMedCentral Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, Saco J, Homet Moreno B, Mezzadra R, Chmielowski B, Ruchalski K, Shintaku IP, Sanchez PJ, Puig-Saus C, Cherry G, Seja E, Kong X, Pang J, Berent-Maoz B, Comin-Anduix B, Graeber TG, Tumeh PC, Schumacher TNM, Lo RS, Ribas A. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819–29. https://​doi.​org/​10.​1056/​NEJMoa1604958.CrossRefPubMedPubMedCentral
44.
go back to reference Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, Jones RE, Kulkarni MM, Kuraguchi M, Palakurthi S, Fecci PE, Johnson BE, Janne PA, Engelman JA, Gangadharan SP, Costa DB, Freeman GJ, Bueno R, Hodi FS, Dranoff G, Wong KK, Hammerman PS. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7(1):10501. https://doi.org/10.1038/ncomms10501.CrossRefPubMedPubMedCentral Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, Jones RE, Kulkarni MM, Kuraguchi M, Palakurthi S, Fecci PE, Johnson BE, Janne PA, Engelman JA, Gangadharan SP, Costa DB, Freeman GJ, Bueno R, Hodi FS, Dranoff G, Wong KK, Hammerman PS. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7(1):10501. https://​doi.​org/​10.​1038/​ncomms10501.CrossRefPubMedPubMedCentral
Metadata
Title
Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung cancer patients: a retrospective multicenter study
Authors
Kazutaka Hosoya
Daichi Fujimoto
Takeshi Morimoto
Toru Kumagai
Akihiro Tamiya
Yoshihiko Taniguchi
Toshihide Yokoyama
Tadashi Ishida
Hirotaka Matsumoto
Katsuya Hirano
Ryota Kominami
Keisuke Tomii
Hidekazu Suzuki
Tomonori Hirashima
Satoshi Tanaka
Junji Uchida
Mitsunori Morita
Masaki Kanazu
Masahide Mori
Kenji Nagata
Ikue Fukuda
Motohiro Tamiya
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08048-4

Other articles of this Issue 1/2021

BMC Cancer 1/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine