Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review
Abstract
:1. Introduction
2. Mechanism of Action of Immune Checkpoint Inhibitors (ICIs)
3. Changes in Treatment of Lung Cancer without Driver-Oncogene Mutations
4. Immune Combination Therapy
4.1. Combination with Chemotherapy
4.2. Combination of ICIs
4.3. Combination with Radiation Therapy
5. Effects on SCLC
6. Biomarkers
7. Long-Term Survival
8. Challenges Associated with ICIs
8.1. Treatment of Patients Harboring a Driver Mutation
8.2. Applicability Among Patients with a History of Interstitial Pneumonia or Autoimmune Disease
8.3. Co-Administration of Steroids
9. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, D.; Mellman, I. Oncology Meets Immunology: The Cancer-Immunity Cycle. Immunity 2013, 39, 1–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schreiber, R.D.; Old, L.J.; Smyth, M.J. Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion. Science 2011, 331, 1565–1570. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Motzer, R.J.; Tannir, N.M.; McDermott, D.F.; Frontera, O.A.; Melichar, B.; Choueiri, T.K.; Plimack, E.R.; Barthelemy, P.; Porta, C.; George, S.; et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2018, 378, 1277–1290. [Google Scholar] [CrossRef]
- Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; Heuvel, M.M.V.D.; Ciuleanu, T.-E.; Badin, F.; et al. First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 376, 2415–2426. [Google Scholar] [CrossRef]
- Hui, E.; Cheung, J.; Zhu, J.; Su, X.; Taylor, M.J.; Wallweber, H.A.; Sasmal, D.K.; Huang, J.; Kim, J.M.; Mellman, I.; et al. T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition. Science 2017, 355, 1428–1433. [Google Scholar] [CrossRef]
- Sansom, D. CD28, CTLA-4 and their ligands: Who does what and to whom? Immunology 2000, 101, 169–177. [Google Scholar] [CrossRef]
- Rowshanravan, B.; Halliday, N.; Sansom, D. CTLA-4: A moving target in immunotherapy. Blood 2018, 131, 58–67. [Google Scholar] [CrossRef]
- Malas, S.; Harrasser, M.; Lacy, K.E.; Karagiannis, S.N. Antibody therapies for melanoma: New and emerging opportunities to activate immunity (Review). Oncol. Rep. 2014, 32, 875–886. [Google Scholar] [CrossRef] [Green Version]
- Walunas, T.L.; Lenschow, D.J.; Bakker, C.Y.; Linsley, P.S.; Freeman, G.J.; Green, J.M.; Thompson, C.B.; Bluestone, J.A. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1994, 1, 405–413. [Google Scholar] [CrossRef]
- Brahmer, J.; Reckamp, K.L.; Baas, P.; Crino, L.; Eberhardt, W.E.; Poddubskaya, E.V.; Antonia, S.; Pluzanski, A.; Vokes, E.E.; Holgado, E.; et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 373, 123–135. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Borghaei, H.; Paz-Ares, L.; Horn, L.A.; Spigel, D.R.; Steins, M.; Ready, N.E.; Chow, L.Q.; Vokes, E.E.; Felip, E.; Holgado, E.; et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 373, 1627–1639. [Google Scholar] [CrossRef] [PubMed]
- Herbst, R.S.; Baas, P.; Kim, N.-W.; Felip, E.; Pérez-Gracia, J.L.; Han, J.-Y.; Molina, J.; Kim, J.-H.; Arvis, C.D.; Ahn, M.-J.; et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016, 387, 1540–1550. [Google Scholar] [CrossRef]
- Rittmeyer, A.; Barlesi, F.; Waterkamp, D.; Park, K.; Ciardiello, F.; Von Pawel, J.; Gadgeel, S.M.; Hida, T.; Kowalski, D.; Dols, M.C.; et al. 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, 255–265. [Google Scholar] [CrossRef]
- Reck, M.; Rodríguez-Abreu, D.; Robinson, A.G.; Hui, R.; Csőszi, T.; Fülöp, A.; Gottfried, M.; Peled, N.; Tafreshi, A.; Cuffe, S.; et al. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2016, 375, 1823–1833. [Google Scholar] [CrossRef] [Green Version]
- Gandhi, L.; Rodríguez-Abreu, D.; Gadgeel, S.; Esteban, E.; Felip, E.; De Angelis, F.; Dómine, M.; Clingan, P.; Hochmair, M.J.; Powell, S.F.; et al. Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 378, 2078–2092. [Google Scholar] [CrossRef]
- Paz-Ares, L.; Luft, A.; Vicente, D.; Tafreshi, A.; Gümüş, M.; Mazieres, J.; Hermes, B.; Çay Şenler, F.; Csőszi, T.; Fülöp, A.; et al. Pembrolizumab plus Chemotherapy for Squamous Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 379, 2040–2051. [Google Scholar] [CrossRef]
- Antonia, S.J.; Villegas, A.; Daniel, D.; Vicente, D.; Murakami, S.; Hui, R.; Yokoi, T.; Chiappori, A.; Lee, K.H.; De Wit, M.; et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 377, 1919–1929. [Google Scholar] [CrossRef]
- Socinski, M.A.; Jotte, R.M.; Cappuzzo, F.; Orlandi, F.; Stroyakovskiy, D.; Nogami, N.; Rodríguez-Abreu, D.; Moro-Sibilot, D.; Thomas, C.A.; Barlesi, F.; et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N. Engl. J. Med. 2018, 378, 2288–2301. [Google Scholar] [CrossRef]
- West, H.; McCleod, M.; Hussein, M.; Morabito, A.; Rittmeyer, A.; Conter, H.J.; Kopp, H.-G.; Daniel, D.; McCune, S.; Mekhail, T.; et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019, 20, 924–937. [Google Scholar] [CrossRef]
- Hellmann, M.D.; Paz-Ares, L.; Caro, R.B.; Zurawski, B.; Kim, S.-W.; Costa, E.C.; Park, K.; Alexandru, A.; Lupinacci, L.; Jimenez, E.D.L.M.; et al. Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2019, 381, 2020–2031. [Google Scholar] [CrossRef] [PubMed]
- Khoja, L.; Day, D.; Chen, T.W.-W.; Siu, L.L.; Hansen, A. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: A systematic review. Ann. Oncol. 2017, 28, 2377–2385. [Google Scholar] [CrossRef] [PubMed]
- Hellmann, M.D.; Ciuleanu, T.-E.; Pluzanski, A.; Lee, J.S.; Otterson, G.A.; Audigier-Valette, C.; Minenza, E.; Linardou, H.; Burgers, S.; Salman, P.; et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N. Engl. J. Med. 2018, 378, 2093–2104. [Google Scholar] [CrossRef] [PubMed]
- Haanen, J.B.A.G.; Carbonnel, F.; Robert, C.; Kerr, K.M.; Peters, S.; Larkin, J.; Jordan, K.; ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2017, 28, iv119–iv142. [Google Scholar] [CrossRef]
- Antonia, S.J.; Villegas, A.; Daniel, D.; Vicente, D.; Murakami, S.; Hui, R.; Kurata, T.; Chiappori, A.; Lee, K.H.; De Wit, M.; et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N. Engl. J. Med. 2018, 379, 2342–2350. [Google Scholar] [CrossRef]
- Reck, M.; Luft, A.; Szczesna, A.; Havel, L.; Kim, S.-W.; Akerley, W.; Pietanza, M.C.; Wu, Y.-L.; Zielinski, C.; Thomas, M.; et al. Phase III Randomized Trial of Ipilimumab Plus Etoposide and Platinum Versus Placebo Plus Etoposide and Platinum in Extensive-Stage Small-Cell Lung Cancer. J. Clin. Oncol. 2016, 34, 3740–3748. [Google Scholar] [CrossRef]
- Horn, L.; Mansfield, A.; Szczęsna, A.; Havel, L.; Krzakowski, M.; Hochmair, M.J.; Huemer, F.; Losonczy, G.; Johnson, M.L.; Nishio, M.; et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 379, 2220–2229. [Google Scholar] [CrossRef]
- Paz-Ares, L.; Dvorkin, M.; Chen, Y.; Reinmuth, N.; Hotta, K.; Trukhin, D.; Statsenko, G.; Hochmair, M.J.; Özgüroğlu, M.; Ji, J.H.; et al. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): A randomised, controlled, open-label, phase 3 trial. Lancet 2019, 394, 1929–1939. [Google Scholar] [CrossRef]
- Yoshimura, A.; Yamada, T.; Miyagawa-Hayashino, A.; Sonobe, Y.; Imabayashi, T.; Yamada, T.; Okada, S.; Shimamoto, T.; Chihara, Y.; Iwasaku, M.; et al. Comparing three different anti-PD-L1 antibodies for immunohistochemical evaluation of small cell lung cancer. Lung Cancer 2019, 137, 108–112. [Google Scholar] [CrossRef]
- Ready, N.; Ott, P.A.; Hellmann, M.D.; Zugazagoitia, J.; Hann, C.L.; De Braud, F.; Antonia, S.J.; Ascierto, P.A.; Moreno, V.; Atmaca, A.; et al. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J. Thorac. Oncol. 2020, 15, 426–435. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hui, R.; Garon, E.B.; Goldman, J.W.; Leighl, N.B.; Hellmann, M.D.; Patnaik, A.; Gandhi, L.; Eder, J.P.; Ahn, M.-J.; Horn, L.; et al. Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: A phase 1 trial. Ann. Oncol. 2017, 28, 874–881. [Google Scholar] [CrossRef] [PubMed]
- Aguilar, E.; Ricciuti, B.; Gainor, J.; Kehl, K.; Kravets, S.; Dahlberg, S.; Nishino, M.; Sholl, L.; Adeni, A.; Subegdjo, S.; et al. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann. Oncol. 2019, 30, 1653–1659. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mok, T.S.; Wu, Y.-L.; Kudaba, I.; Kowalski, D.M.; Cho, B.C.; Turna, H.Z.; Castro, G.; Srimuninnimit, V.; Laktionov, K.P.; Bondarenko, I.; et al. 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, 1819–1830. [Google Scholar] [CrossRef]
- Park, S.; Choi, Y.-D.; Kim, J.; Kho, B.-G.; Park, C.-K.; Oh, I.-J.; Kim, Y.-C. Efficacy of immune checkpoint inhibitors according to PD-L1 tumor proportion scores in non-small cell lung cancer. Thorac. Cancer 2019, 11, 408–414. [Google Scholar] [CrossRef]
- McGranahan, N.; Furness, A.J.S.; Rosenthal, R.; Ramskov, S.; Lyngaa, R.; Saini, S.K.; Jamal-Hanjani, M.; Wilson, G.A.; Birkbak, N.J.; Hiley, C.; et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016, 351, 1463–1469. [Google Scholar] [CrossRef] [Green Version]
- Teng, M.W.; Ngiow, S.F.; Ribas, A.; Smyth, M.J. Classifying Cancers Based on T-cell Infiltration and PD-L1. Cancer Res. 2015, 75, 2139–2145. [Google Scholar] [CrossRef] [Green Version]
- Rosenberg, S.A.; Restifo, N.P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015, 348, 62–68. [Google Scholar] [CrossRef] [Green Version]
- Shitara, K.; De Braud, F.; Mandalà, M.; Fornaro, L.; Olesiński, T.; Caglevic, C.; Muro, K.; Mansoor, W.; McDermott, R.; Chen, X.; et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): A randomised, open-label, controlled, phase 3 trial. Lancet 2018, 392, 123–133. [Google Scholar] [CrossRef]
- Adams, S.; Schmid, P.; Rugo, H.; Winer, E.; Loirat, D.; Awada, A.; Cescon, D.; Iwata, H.; Campone, M.; Nanda, R.; et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: Cohort A of the phase II KEYNOTE-086 study. Ann. Oncol. 2019, 30, 397–404. [Google Scholar] [CrossRef] [Green Version]
- Gibbons, D.L.; Byers, L.A.; Kurie, J.M. Smoking, p53 mutation, and lung cancer. Mol. Cancer Res. 2014, 12, 3–13. [Google Scholar] [CrossRef] [Green Version]
- Gainor, J.F.; Shaw, A.T.; Sequist, L.V.; Fu, X.; Azzoli, C.G.; Piotrowska, Z.; Huynh, T.G.; Zhao, L.; Fulton, L.; Schultz, K.R.; et al. EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis. Clin. Cancer Res. 2016, 22, 4585–4593. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ready, N.; Hellmann, M.D.; Awad, M.M.; Otterson, G.A.; Gutierrez, M.; Gainor, J.F.; Borghaei, H.; Jolivet, J.; Horn, L.; Mates, M.; et al. First-Line Nivolumab Plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers. J. Clin. Oncol. 2019, 37, 992–1000. [Google Scholar] [CrossRef] [PubMed]
- Jeyakumar, G.; Kim, S.; Bumma, N.; Landry, C.; Silski, C.; Suisham, S.; Dickow, B.; Heath, E.I.; Fontana, J.; Vaishampayan, U. Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy. J. Immunother. Cancer 2017, 5, 82. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.C.; Karpinets, T.V.; Prieto, P.A.; Vicente, D.; Hoffman, K.; Wei, S.C.; et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science 2017, 359, 97–103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sears, C.; Pardoll, E.M. The intestinal microbiome influences checkpoint blockade. Nat. Med. 2018, 24, 254–255. [Google Scholar] [CrossRef]
- Lang, D.; Horner, A.; Brehm, E.; Akbari, K.; Hergan, B.; Langer, K.; Asel, C.; Scala, M.; Kaiser, B.; Lamprecht, B. Early serum tumor marker dynamics predict progression-free and overall survival in single PD-1/PD-L1 inhibitor treated advanced NSCLC—A retrospective cohort study. Lung Cancer 2019, 134, 59–65. [Google Scholar] [CrossRef]
- Shoji, F.; Takeoka, H.; Kozuma, Y.; Toyokawa, G.; Yamazaki, K.; Ichiki, M.; Takeo, S. Pretreatment prognostic nutritional index as a novel biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors. Lung Cancer 2019, 136, 45–51. [Google Scholar] [CrossRef]
- Maher, V.E.; Fernandes, L.L.; Weinstock, C.; Tang, S.; Agarwal, S.; Brave, M.; Ning, Y.-M.; Singh, H.; Suzman, D.; Xu, J.; et al. Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody. J. Clin. Oncol. 2019, 37, 2730–2737. [Google Scholar] [CrossRef]
- Gettinger, S.; Borghaei, H.; Brahmer, J.; Chow, L.; Burgio, M.; Carpeno, J.D.C.; Pluzanski, A.; Arrieta, O.; Frontera, O.A.; Chiari, R.; et al. OA14.04 Five-Year Outcomes From the Randomized, Phase 3 Trials CheckMate 017/057: Nivolumab vs. Docetaxel in Previously Treated NSCLC. J. Thorac. Oncol. 2019, 14, 244–245. [Google Scholar] [CrossRef]
- Garon, E.B.; Hellmann, M.D.; Rizvi, N.A.; Carcereny, E.; Leighl, N.B.; Ahn, M.-J.; Eder, J.P.; Balmanoukian, A.S.; Aggarwal, C.; Horn, L.; et al. Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J. Clin. Oncol. 2019, 37, 2518–2527. [Google Scholar] [CrossRef]
- Rizvi, H.; Plodkowski, A.J.; Tenet, M.; Halpenny, D.; Long, N.; Sauter, J.L.; Sanchez-Vega, F.; Chatila, W.; Schultz, N.; Ladanyi, M.; et al. Clinical and molecular features predicting long-term response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC. J. Clin. Oncol. 2018, 36, 9022. [Google Scholar] [CrossRef]
- Hastings, K.; Yu, H.; Wei, W.; Sanchez-Vega, F.; Deveaux, M.; Choi, J.; Rizvi, H.; Lisberg, A.; Truini, A.; Lydon, C.; et al. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer. Ann. Oncol. 2019, 30, 1311–1320. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fujimoto, D.; Yomota, M.; Sekine, A.; Morita, M.; Morimoto, T.; Hosomi, Y.; Ogura, T.; Tomioka, H.; Tomii, K. Nivolumab for advanced non-small cell lung cancer patients with mild idiopathic interstitial pneumonia: A multicenter, open-label single-arm phase II trial. Lung Cancer 2019, 134, 274–278. [Google Scholar] [CrossRef] [PubMed]
- Kanai, O.; Kim, Y.H.; Demura, Y.; Kanai, M.; Ito, T.; Fujita, K.; Yoshida, H.; Akai, M.; Mio, T.; Hirai, T. Efficacy and safety of nivolumab in non-small cell lung cancer with preexisting interstitial lung disease. Thorac. Cancer 2018, 9, 847–855. [Google Scholar] [CrossRef] [PubMed]
- Leonardi, G.C.; Gainor, J.F.; Altan, M.; Kravets, S.; Dahlberg, S.E.; Gedmintas, L.; Azimi, R.; Rizvi, H.; Riess, J.W.; Hellmann, M.D.; et al. Safety of Programmed Death–1 Pathway Inhibitors Among Patients With Non–Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. J. Clin. Oncol. 2018, 36, 1905–1912. [Google Scholar] [CrossRef] [PubMed]
- Bianchi, M.; Meng, C.; Ivashkiv, L.B. Inhibition of IL-2-induced Jak-STAT signaling by glucocorticoids. Proc. Natl. Acad. Sci. USA 2000, 97, 9573–9578. [Google Scholar] [CrossRef] [Green Version]
- Im, S.J.; Hashimoto, M.; Gerner, M.Y.; Lee, J.; Kissick, H.T.; Burger, M.C.; Shan, Q.; Hale, J.S.; Lee, J.; Nasti, T.H.; et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 2016, 537, 417–421. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Murakami, T.; Oppenheim, J.J.; Howard, O. Differential response of murine CD4+CD25+and CD4+CD25-T cells to dexamethasone-induced cell death. Eur. J. Immunol. 2004, 34, 859–869. [Google Scholar] [CrossRef]
- Chen, X.; Oppenheim, J.J.; Ortaldo, J.R.; Howard, O.; Winkler-Pickett, R.T. Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3+CD4+CD25+ T regulatory cellsin vivo and enhances their capacity to suppress EAE. Eur. J. Immunol. 2006, 36, 2139–2149. [Google Scholar] [CrossRef]
- Ricciuti, B.; Dahlberg, S.E.; Adeni, A.; Sholl, L.M.; Nishino, M.; Awad, M.M. Immune Checkpoint Inhibitor Outcomes for Patients with Non–Small-Cell Lung Cancer Receiving Baseline Corticosteroids for Palliative Versus Nonpalliative Indications. J. Clin. Oncol. 2019, 37, 1927–1934. [Google Scholar] [CrossRef]
- Santini, F.C.; Rizvi, H.; Plodkowski, A.J.; Ni, A.; Lacouture, M.E.; Gambarin-Gelwan, M.; Wilkins, O.; Panora, E.; Halpenny, D.F.; Long, N.M.; et al. Safety and Efficacy of Re-treating with Immunotherapy after Immune-Related Adverse Events in Patients with NSCLC. Cancer Immunol. Res. 2018, 6, 1093–1099. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Horvat, T.; Adel, N.G.; Dang, T.-O.; Momtaz, P.; Postow, M.A.; Callahan, M.K.; Carvajal, R.D.; Dickson, M.A.; D’Angelo, S.P.; Woo, K.M.; et al. Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center. J. Clin. Oncol. 2015, 33, 3193–3198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Trial | Patient Population | Treatment Regimen | Primary Outcome Results |
---|---|---|---|
CheckMate 017 | Stage IIIB/IV squamous NSCLC; disease recurrence after platinum-based chemotherapy | Nivolumab | Median OS: 9.2 months (95% CI: 7.3–13.3); 12 months OS: 42% (95% CI: 34–50%) |
CheckMate 057 | Stage IIIB/IV non-squamous NSCLC; disease recurrence after platinum-based chemotherapy | Nivolumab | Median OS: 12.2 months (95% CI: 9.7–15.1); 18 months OS: 39% (95% CI: 34–45%) |
OAK | Stage IIIB/IV; disease progression after platinum-based chemotherapy | Atezolizumab | Median OS: 13.8 months (95% CI: 11.8–15.7); PP-ITT; improved OS/PFS in patients with PD-L1 expression > 1% |
IMpower 150 | Stage IIIB/IV; untreated metastatic non-squamous NSCLC | Chemotherapy + Bevacizumab ± Atezolizumab | Median PFS: 8.3 months (95% CI: 7.7–9.8); Median OS: 19.8 months (95% CI: 17.4–24.2) |
KEYNOTE 024 | Stage IV; untreated disease; PD-L1 expression > 50% | Pembrolizumab | Median PFS: 10.3 months (95% CI: 6.7–NR); 6 months PFS: 62.1% (95% CI: 53.8–69.4%) |
KEYNOTE 189 | Stage IIIB/IV; untreated metastatic non-squamous NSCLC | Chemotherapy ± Pembrolizumab | Median OS: 22.0 months (95% CI: 19.5–25.2); 12 months OS: 69.2% (95% CI: 64.1–73.8%) |
KEYNOTE 407 | Stage IIIB/IV; untreated metastatic squamous NSCLC | Chemotherapy ± Pembrolizumab | Median OS: 15.9 months (95% CI: 13.2–NR); 12 months OS: 65.2% (95% CI: 57.7–71.6%) |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Onoi, K.; Chihara, Y.; Uchino, J.; Shimamoto, T.; Morimoto, Y.; Iwasaku, M.; Kaneko, Y.; Yamada, T.; Takayama, K. Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review. J. Clin. Med. 2020, 9, 1362. https://doi.org/10.3390/jcm9051362
Onoi K, Chihara Y, Uchino J, Shimamoto T, Morimoto Y, Iwasaku M, Kaneko Y, Yamada T, Takayama K. Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review. Journal of Clinical Medicine. 2020; 9(5):1362. https://doi.org/10.3390/jcm9051362
Chicago/Turabian StyleOnoi, Keisuke, Yusuke Chihara, Junji Uchino, Takayuki Shimamoto, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko Kaneko, Tadaaki Yamada, and Koichi Takayama. 2020. "Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review" Journal of Clinical Medicine 9, no. 5: 1362. https://doi.org/10.3390/jcm9051362