Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 7/2019

29.05.2019 | Original Article – Clinical Oncology

Exceptional pemetrexed sensitivity can predict therapeutic benefit from subsequent chemotherapy in metastatic non-squamous non-small cell lung cancer

verfasst von: Ji Hyun Park, Byoung Soo Kwon, So Jung Park, Wonjun Ji, Shinkyo Yoon, Chang-Min Choi, Jae Cheol Lee

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Based on an exceptionally durable response to pemetrexed observed in some patients with metastatic NSCLC, the predictive value of pemetrexed sensitivity to outcomes of subsequent systemic treatment was investigated.

Methods

We retrospectively reviewed the patients with metastatic non-squamous NSCLC treated with pemetrexed monotherapy as their first- or second-line chemotherapy between November 2006 and February 2015. Good (top 5% longest) and poor responders (bottom 12% shortest) were defined according to the duration of pemetrexed maintenance. The first and second post-pemetrexed (PP) systemic treatments were defined as PP1 and PP2 therapies, respectively, to define their progression-free survivals (PFS) as PFS1 and PFS2.

Results

In a total of 100 patients, 86% of patients received pemetrexed as their second-line chemotherapy, and 34% were classified as good responders. Good and poor responder groups showed 20.5 months and 0.7 months of the median duration of responses, respectively. PP1 and PP2 therapies were done in 74% and 41.9% of patients after failure to pemetrexed. To our surprise, disease control rate (DCR) was significantly higher in the good responder group than poor responder group (69.6% vs 37.3%, p = 0.010) in patients treated with PP1 therapy, and median PFS1 was also significantly longer (5.2 vs 2.2 months, p < 0.01) regardless of the type of subsequent systemic treatment. Meanwhile, pemetrexed sensitivity did not affect DCR or PFS of patients who received PP2 therapies.

Conclusions

Patients who achieved durable response to pemetrexed might obtain greater therapeutic benefits from subsequent systemic treatment in metastatic non-squamous NSCLC without targets, which could potentiate more effective post-pemetrexed treatment strategy.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Adjei AA (2004) Pharmacology and mechanism of action of pemetrexed. Clinical Lung Cancer 5(Suppl 2):S51–55CrossRefPubMed Adjei AA (2004) Pharmacology and mechanism of action of pemetrexed. Clinical Lung Cancer 5(Suppl 2):S51–55CrossRefPubMed
Zurück zum Zitat Barlesi F, Mazieres J, Merlio J-P, Debieuvre D, Mosser J, Lena H, Ouafik LH, Besse B, Rouquette I, Westeel V, Escande F, Monnet I, Lemoine A, Veillon R, Blons H, Audigier-Valette C, Bringuier P-P, Lamy R, Beau-Faller M, Pujol J-L, Sabourin J-C, Penault-Llorca F, Denis MG, Lantuejoul S, Morin F, Tran Q, Missy P, Langlais A, Milleron B, Cadranel J, Soria J-C, Zalcman G (2016) Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). The Lancet 387(10026):1415–1426. https://doi.org/10.1016/S0140-6736(16)00004-0 CrossRef Barlesi F, Mazieres J, Merlio J-P, Debieuvre D, Mosser J, Lena H, Ouafik LH, Besse B, Rouquette I, Westeel V, Escande F, Monnet I, Lemoine A, Veillon R, Blons H, Audigier-Valette C, Bringuier P-P, Lamy R, Beau-Faller M, Pujol J-L, Sabourin J-C, Penault-Llorca F, Denis MG, Lantuejoul S, Morin F, Tran Q, Missy P, Langlais A, Milleron B, Cadranel J, Soria J-C, Zalcman G (2016) Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). The Lancet 387(10026):1415–1426. https://​doi.​org/​10.​1016/​S0140-6736(16)00004-0 CrossRef
Zurück zum Zitat 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, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR (2015) Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med 373(17):1627–1639. 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, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR (2015) Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med 373(17):1627–1639. https://​doi.​org/​10.​1056/​NEJMoa1507643 CrossRefPubMedPubMedCentral
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 11). Eur J Cancer (Oxford, Engl: 1990) 45(2):228–247CrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 11). Eur J Cancer (Oxford, Engl: 1990) 45(2):228–247CrossRef
Zurück zum Zitat Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378(22):2078–2092. https://doi.org/10.1056/NEJMoa1801005 CrossRefPubMed Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378(22):2078–2092. https://​doi.​org/​10.​1056/​NEJMoa1801005 CrossRefPubMed
Zurück zum Zitat Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, Sequist LV, Smith DC, Leming P, Carbone DP, Pinder-Schenck MC, Topalian SL, Hodi FS, Sosman JA, Sznol M, McDermott DF, Pardoll DM, Sankar V, Ahlers CM, Salvati M, Wigginton JM, Hellmann MD, Kollia GD, Gupta AK, Brahmer JR (2015) Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol 33(18):2004–U2032. https://doi.org/10.1200/jco.2014.58.3708 CrossRefPubMedPubMedCentral Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, Sequist LV, Smith DC, Leming P, Carbone DP, Pinder-Schenck MC, Topalian SL, Hodi FS, Sosman JA, Sznol M, McDermott DF, Pardoll DM, Sankar V, Ahlers CM, Salvati M, Wigginton JM, Hellmann MD, Kollia GD, Gupta AK, Brahmer JR (2015) Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol 33(18):2004–U2032. https://​doi.​org/​10.​1200/​jco.​2014.​58.​3708 CrossRefPubMedPubMedCentral
Zurück zum Zitat Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet (Lond Engl) 387(10027):1540–1550. https://doi.org/10.1016/s0140-6736(15)01281-7 CrossRef Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet (Lond Engl) 387(10027):1540–1550. https://​doi.​org/​10.​1016/​s0140-6736(15)01281-7 CrossRef
Zurück zum Zitat Kano Y, Akutsu M, Tsunoda S, Izumi T, Kobayashi H, Inoue K, Mori K, Fujii H, Mano H, Odgerel T, Furukawa Y (2006) Schedule-dependent interactions between pemetrexed and cisplatin in human carcinoma cell lines in vitro. Oncol Res 16(2):85–95CrossRefPubMed Kano Y, Akutsu M, Tsunoda S, Izumi T, Kobayashi H, Inoue K, Mori K, Fujii H, Mano H, Odgerel T, Furukawa Y (2006) Schedule-dependent interactions between pemetrexed and cisplatin in human carcinoma cell lines in vitro. Oncol Res 16(2):85–95CrossRefPubMed
Zurück zum Zitat 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 (2016) Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun 7:9. https://doi.org/10.1038/ncomms10501 CrossRef 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 (2016) Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun 7:9. https://​doi.​org/​10.​1038/​ncomms10501 CrossRef
Zurück zum Zitat Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang J-J, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957. https://doi.org/10.1056/NEJMoa0810699 CrossRefPubMed Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang J-J, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957. https://​doi.​org/​10.​1056/​NEJMoa0810699 CrossRefPubMed
Zurück zum Zitat Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2013) PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 31(23):2895. https://doi.org/10.1200/jco.2012.47.1102 CrossRefPubMed Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2013) PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 31(23):2895. https://​doi.​org/​10.​1200/​jco.​2012.​47.​1102 CrossRefPubMed
Zurück zum Zitat Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR (2016a) Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med 375(19):1823–1833. https://doi.org/10.1056/NEJMoa1606774 CrossRefPubMed Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR (2016a) Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med 375(19):1823–1833. https://​doi.​org/​10.​1056/​NEJMoa1606774 CrossRefPubMed
Zurück zum Zitat Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR (2016b) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375(19):1823–1833. https://doi.org/10.1056/NEJMoa1606774 CrossRefPubMed Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR (2016b) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375(19):1823–1833. https://​doi.​org/​10.​1056/​NEJMoa1606774 CrossRefPubMed
Zurück zum Zitat Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13(3):239–246. https://doi.org/10.1016/S1470-2045(11)70393-X CrossRefPubMed Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13(3):239–246. https://​doi.​org/​10.​1016/​S1470-2045(11)70393-X CrossRefPubMed
Metadaten
Titel
Exceptional pemetrexed sensitivity can predict therapeutic benefit from subsequent chemotherapy in metastatic non-squamous non-small cell lung cancer
verfasst von
Ji Hyun Park
Byoung Soo Kwon
So Jung Park
Wonjun Ji
Shinkyo Yoon
Chang-Min Choi
Jae Cheol Lee
Publikationsdatum
29.05.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-02941-z

Weitere Artikel der Ausgabe 7/2019

Journal of Cancer Research and Clinical Oncology 7/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.