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Response to the treatment immediately before nivolumab monotherapy may predict clinical response to nivolumab in patients with non-small cell lung cancer

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Currently, no markers predictive of response to nivolumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) are currently recognized in Japan. The present study was undertaken to identify such markers.

Materials and methods

Medical records of 50 patients with advanced NSCLC and treated with nivolumab monotherapy at Shizuoka Cancer Center between December 2015 and April 2016 were retrospectively reviewed. The parameters studied were age, sex, Eastern Cooperative Oncology Group performance status, smoking history, histological diagnosis, epidermal growth factor receptor or anaplastic lymphoma kinase status, therapeutic line of nivolumab, efficacy of treatment immediately before nivolumab monotherapy, and time since previous therapy.

Results

The objective response rate to nivolumab monotherapy was 18% [95% confidence interval (CI) 10–31]. Multivariate logistic regression identified “squamous histology” [odds ratio (OR) 0.00054; 95% CI 0–0.27] and “response to the treatment immediately before nivolumab monotherapy” (OR 0.0011; 95% CI 0–0.092) as independently associated with response to nivolumab monotherapy.

Conclusion

“Response to the treatment immediately before nivolumab monotherapy” might be a predictive marker of response to nivolumab in patients with advanced NSCLC.

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References

  1. Shepherd FA, Dancey J, Ramlau R et al (2000) Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 18:2095–2103

    Article  CAS  PubMed  Google Scholar 

  2. Brahmer J, Reckamp KL, Baas P et al (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373:123–135. doi:10.1056/NEJMoa1504627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Borghaei H, Paz-Ares L, Horn L et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373:1627–1639. doi:10.1056/NEJMoa1507643

    Article  CAS  PubMed  Google Scholar 

  4. Makoto N, Toyoaki H, Kazuhiko N et al (2015) Phase II studies of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients with advanced squamous (sq) or nonsquamous (non-sq) non-small cell lung cancer (NSCLC). J Clin Oncol 33(suppl):abstr8027

    Google Scholar 

  5. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. doi:10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  6. Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454. doi:10.1056/NEJMoa1200690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Herbst RS, Baas P, Kim DW et al (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:1540–1550. doi:10.1016/S0140-6736(15)01281-7

    Article  CAS  PubMed  Google Scholar 

  8. Tumeh PC, Harview CL, Yearley JH et al (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515:568–571. doi:10.1038/nature13954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rizvi NA, Hellmann MD, Snyder A et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128. doi:10.1126/science.aaa1348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Le DT, Uram JN, Wang H et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520. doi:10.1056/NEJMoa1500596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. McGranahan N, Furness AJ, Rosenthal R et al (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351:1463–1469. doi:10.1126/science.aaf1490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Reck M, Rodriguez-Abreu D, Robinson AG et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823–1833. doi:10.1056/NEJMoa1606774

    Article  CAS  PubMed  Google Scholar 

  13. Barlesi F, Park K, Ciardiello F et al (2016) Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. Ann Oncol 27[Suppl 6]:vi552–vi587

    Google Scholar 

  14. Obeid M, Panaretakis T, Tesniere A et al (2007) Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from “silent” to immunogenic. Cancer Res 67:7941–7944. doi:10.1158/0008-5472.CAN-07-1622

    Article  CAS  PubMed  Google Scholar 

  15. Apetoh L, Ghiringhelli F, Tesniere A et al (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13:1050–1059. doi:10.1038/nm1622

    Article  CAS  PubMed  Google Scholar 

  16. Zitvogel L, Kepp O, Kroemer G (2011) Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8:151–160. doi:10.1038/nrclinonc.2010.223

    Article  CAS  PubMed  Google Scholar 

  17. Mole RH (1953) Whole body irradiation; radiobiology or medicine? Br J Radiol 26:234–241. doi:10.1259/0007-1285-26-305-234

    Article  CAS  PubMed  Google Scholar 

  18. Lee Y, Auh SL, Wang Y et al (2009) Therapeutic effects of ablative radiation on local tumor require CD8 + T cells: changing strategies for cancer treatment. Blood 114:589–595. doi:10.1182/blood-2009-02-206870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lugade AA, Moran JP, Gerber SA et al (2005) Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol 174:7516–7523

    Article  CAS  PubMed  Google Scholar 

  20. Nesslinger NJ, Sahota RA, Stone B et al (2007) Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res 13:1493–1502. doi:10.1158/1078-0432.CCR-06-1772

    Article  CAS  PubMed  Google Scholar 

  21. Schaue D, Comin-Anduix B, Ribas A et al (2008) T-cell responses to survivin in cancer patients undergoing radiation therapy. Clin Cancer Res 14:4883–4890. doi:10.1158/1078-0432.CCR-07-4462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schaue D, Ratikan JA, Iwamoto KS et al (2012) Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys 83:1306–1310. doi:10.1016/j.ijrobp.2011.09.049

    Article  CAS  PubMed  Google Scholar 

  23. Dewan MZ, Galloway AE, Kawashima N et al (2009) Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 15:5379–5388. doi:10.1158/1078-0432.CCR-09-0265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lee W, Jiang Z, Liu J et al (2010) The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465:473–477. doi:10.1038/nature09004

    Article  CAS  PubMed  Google Scholar 

  25. Timmermann B, Kerick M, Roehr C et al (2010) Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis. PLoS One 5:e15661. doi:10.1371/journal.pone.0015661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cancer Genome Atlas N (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–337. doi:10.1038/nature11252

    Article  Google Scholar 

  27. Larkin J, Lao CD, Urba WJ et al (2015) Efficacy and safety of nivolumab in patients with BRAF V600 mutant and BRAF wild-type advanced melanoma: a pooled analysis of 4 clinical trials. JAMA Oncol 1:433–440. doi:10.1001/jamaoncol.2015.1184

    Article  PubMed  Google Scholar 

  28. Gettinger S, Rizvi NA, Chow LQ et al (2016) Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung Cancer. J Clin Oncol 34:2980–2987. doi:10.1200/JCO.2016.66.9929

    Article  CAS  PubMed  Google Scholar 

  29. Gainor JF, Shaw AT, Sequist LV et al (2016) 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 22:4585–4593. doi:10.1158/1078-0432.CCR-15-3101

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka, 411-8777, Japan

    Haruki Kobayashi, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami & Toshiaki Takahashi

  2. Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan

    Masahiro Endo

Authors
  1. Haruki Kobayashi
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  2. Shota Omori
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  3. Kazuhisa Nakashima
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  4. Kazushige Wakuda
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  5. Akira Ono
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  6. Hirotsugu Kenmotsu
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  7. Tateaki Naito
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  8. Haruyasu Murakami
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  10. Toshiaki Takahashi
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Contributions

Dr. Kobayashi is the guarantor of the article. Dr. Kobayashi contributed to conceiving the study design, performing the data analysis, and producing the initial draft of the manuscript; participated in data generation, interpretation of the analysis, final preparation of the manuscript; read and approved the final manuscript. Dr. Omori contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Nakashima contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Wakuda contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Ono contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Kenmotsu contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Naito contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Murakami contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Endo contributed to interpretation of the analysis and final preparation of the manuscript; read and approved the final manuscript. Dr. Takahashi contributed to conceiving the study design and producing the initial draft of the manuscript; participated in interpretation of the analysis, final preparation of the manuscript; read and approved the final manuscript.

Corresponding author

Correspondence to Haruki Kobayashi.

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Conflict of interest

HK reports honoraria from Eli Lilly and Taiho Pharmaceutical. SO reports honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Boehringer Ingelheim, and Taiho Pharmaceutical. KN reports honoraria from Eli Lilly, Ono Pharmaceutical, Mochida Pharmaceutical, and Taiho Pharmaceutical. KW reports honoraria from Taiho Pharmaceutical, Boehringer Ingelheim, and Ono Pharmaceutical. AO reports honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, and Takeda Pharmaceutical. HK reports honoraria from Ono Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Chugai Pharmaceutical, Bristol-Myers, Taiho Pharmaceutical, and Kyowa Hakko Kirin, and research funding from AstraZeneca and Boehringer Ingelheim. TN reports honoraria from Ono Pharmaceutical. HM reports honoraria from Chugai Pharmaceutical, Pfizer, Novartis, Boehringer Ingelheim, Taiho Pharmaceutical, AstraZeneca, Eli Lilly, Ono Pharmaceutical, Bristol-Myers, and Astellas. EM reports honoraria from Ono Pharmaceutical. TT reports honoraria from Ono Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, and Chugai Pharmaceutical, and research funding from Ono Pharmaceutical, AstraZeneca, Eli Lilly, Chugai Pharmaceutical, Pfizer, Takeda Pharmaceutical, Taiho Pharmaceutical, and MSD.

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Kobayashi, H., Omori, S., Nakashima, K. et al. Response to the treatment immediately before nivolumab monotherapy may predict clinical response to nivolumab in patients with non-small cell lung cancer. Int J Clin Oncol 22, 690–697 (2017). https://doi.org/10.1007/s10147-017-1118-x

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  • DOI: https://doi.org/10.1007/s10147-017-1118-x

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