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Erschienen in: Clinical and Translational Oncology 7/2019

18.12.2018 | Research Article

Benefit of ablative versus palliative-only radiotherapy in combination with nivolumab in patients affected by metastatic kidney and lung cancer

Erschienen in: Clinical and Translational Oncology | Ausgabe 7/2019

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Abstract

Purpose

Here, we present the results from a retrospective analysis, with the purpose of evaluating the safety and feasibility of nivolumab and radiotherapy (RT) concomitant association in metastatic kidney and lung cancer patients.

Materials and methods

From August 2015 until September 2017, we retrospectively observed 20 patients with metastatic lung and renal cell carcinoma who had been initiated therapy with nivolumab and underwent concomitant RT. RT was administered either as an ablative therapy in the oligometastatic/oligoprogressive setting or as palliative-only treatment for symptomatic patients. Data on progression-free and overall survival (PFS and OS), treatment response and adverse events were collected and reported. Comparison between palliative-only and ablative treatments was performed.

Results

PFS and OS were 7 and 12.5 months in the entire population, respectively. Oligoprogressive patients treated with ablative intent, compared to patients undergoing RT with palliative-only intent, had statistically longer PFS (11.5 vs 5.2 months, HR 0.42, CI 0.18–0.98, p 0.03) and OS (17.9 vs 10.31 months, HR 0.41 CI 0.16–1.02, p 0.04). Considering only patients treated with ablative intent, 87.5% showed response to treatment, and complete response was reported in 37.5% of cases. Adverse G2–G3 related to combination treatment were reported as follows: 1 gastrointestinal (nausea), 4 breakthrough pain.

Conclusions

Our data showed significant advantage for oligoprogressive patients treated with RT during nivolumab therapy. No safety alert emerged. These results underline the potential synergistic effects of RT and Immune therapy combination. Our analysis prompts further prospective studies exploring the benefit of integrated treatment strategies.
Literatur
1.
Zurück zum Zitat Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75.CrossRefPubMedPubMedCentral Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2:846–56.CrossRefPubMed Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2:846–56.CrossRefPubMed
3.
Zurück zum Zitat Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.CrossRefPubMedPubMedCentral Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.CrossRefPubMedPubMedCentral Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.CrossRefPubMedPubMedCentral Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.CrossRefPubMedPubMedCentral
6.
7.
Zurück zum Zitat Garnett CT, Palena C, Chakraborty M, et al. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res. 2004;64(21):7985–94.CrossRefPubMed Garnett CT, Palena C, Chakraborty M, et al. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res. 2004;64(21):7985–94.CrossRefPubMed
8.
Zurück zum Zitat Lugade AA, Sorensen EW, Gerber SA, et al. Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J Immunol. 2008;180(5):3132–9.CrossRefPubMed Lugade AA, Sorensen EW, Gerber SA, et al. Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J Immunol. 2008;180(5):3132–9.CrossRefPubMed
9.
Zurück zum Zitat Filatenkov A, Baker J, Mueller AM, et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin Cancer Res. 2015;21(16):3727–39.CrossRefPubMedPubMedCentral Filatenkov A, Baker J, Mueller AM, et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin Cancer Res. 2015;21(16):3727–39.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Shiraishi K, Ishiwata Y, Nakagawa K, et al. Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1alpha. Clin Cancer Res. 2008;14(4):1159–66.CrossRefPubMed Shiraishi K, Ishiwata Y, Nakagawa K, et al. Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1alpha. Clin Cancer Res. 2008;14(4):1159–66.CrossRefPubMed
11.
Zurück zum Zitat Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366(10):925–31.CrossRefPubMedPubMedCentral Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366(10):925–31.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Golden EB, Demaria S, Schiff PB, et al. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res. 2013;1(6):365–72.CrossRefPubMedPubMedCentral Golden EB, Demaria S, Schiff PB, et al. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res. 2013;1(6):365–72.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
14.
Zurück zum Zitat Levy A, Massard C, Soria JC, et al. Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: single centre subset analysis from a phase 1/2 trial. Eur J Cancer. 2016;68:156–62.CrossRefPubMed Levy A, Massard C, Soria JC, et al. Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: single centre subset analysis from a phase 1/2 trial. Eur J Cancer. 2016;68:156–62.CrossRefPubMed
15.
Zurück zum Zitat Bang A, Wilhite TJ, Pike LRG, et al. Multicenter evaluation of the tolerability of combined treatment with PD-1 and CTLA-4 immune checkpoint inhibitors and palliative radiation therapy. Int J Radiat Oncol Biol Phys. 2017;98(2):344–51.CrossRefPubMed Bang A, Wilhite TJ, Pike LRG, et al. Multicenter evaluation of the tolerability of combined treatment with PD-1 and CTLA-4 immune checkpoint inhibitors and palliative radiation therapy. Int J Radiat Oncol Biol Phys. 2017;98(2):344–51.CrossRefPubMed
16.
Zurück zum Zitat Luke JJ, Lemons JM, Karrison TG, et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors. J Clin Oncol. 2018;36(16):1611–8.CrossRefPubMedPubMedCentral Luke JJ, Lemons JM, Karrison TG, et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors. J Clin Oncol. 2018;36(16):1611–8.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Pike LRG, Bang A, Ott P, et al. Radiation and PD-1 inhibition: favorable outcomes after brain-directed radiation. Radiother Oncol. 2017;124(1):98–103.CrossRefPubMed Pike LRG, Bang A, Ott P, et al. Radiation and PD-1 inhibition: favorable outcomes after brain-directed radiation. Radiother Oncol. 2017;124(1):98–103.CrossRefPubMed
18.
Zurück zum Zitat Chen L, Douglass J, Kleinberg L, et al. Concurrent immune checkpoint inhibitors and stereotactic radiosurgery for brain metastases in non-small cell lung cancer, melanoma, and renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2018;100(4):916–25.CrossRefPubMed Chen L, Douglass J, Kleinberg L, et al. Concurrent immune checkpoint inhibitors and stereotactic radiosurgery for brain metastases in non-small cell lung cancer, melanoma, and renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2018;100(4):916–25.CrossRefPubMed
19.
Zurück zum Zitat Hubbeling HG, Schapira EF, Horick NK, et al. Safety of combined PD-1 pathway inhibition and intracranial radiation therapy in non-small cell lung cancer. J Thorac Oncol. 2018;13(4):550–8.CrossRefPubMed Hubbeling HG, Schapira EF, Horick NK, et al. Safety of combined PD-1 pathway inhibition and intracranial radiation therapy in non-small cell lung cancer. J Thorac Oncol. 2018;13(4):550–8.CrossRefPubMed
20.
Zurück zum Zitat Horn L, Spigel DR, Vokes EE, et al. 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.CrossRefPubMedPubMedCentral Horn L, Spigel DR, Vokes EE, et al. 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.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Escudier B, Motzer RJ, Sharma P, et al. Treatment beyond progression in patients with advanced renal cell carcinoma treated with Nivolumab in CheckMate 025. Eur Urol. 2017;72(3):368–76.CrossRefPubMed Escudier B, Motzer RJ, Sharma P, et al. Treatment beyond progression in patients with advanced renal cell carcinoma treated with Nivolumab in CheckMate 025. Eur Urol. 2017;72(3):368–76.CrossRefPubMed
22.
Zurück zum Zitat Nomura M, Otsuka A, Yoshimura M, et al. Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. Cancer Chemother Pharmacol. 2018;81(5):823–7.CrossRefPubMed Nomura M, Otsuka A, Yoshimura M, et al. Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. Cancer Chemother Pharmacol. 2018;81(5):823–7.CrossRefPubMed
24.
Zurück zum Zitat Popp I, Grosu AL, Niedermann G, et al. Immune modulation by hypofractionated stereotactic radiation therapy: therapeutic implications. Radiother Oncol. 2016;120(2):185–94.CrossRefPubMed Popp I, Grosu AL, Niedermann G, et al. Immune modulation by hypofractionated stereotactic radiation therapy: therapeutic implications. Radiother Oncol. 2016;120(2):185–94.CrossRefPubMed
Metadaten
Titel
Benefit of ablative versus palliative-only radiotherapy in combination with nivolumab in patients affected by metastatic kidney and lung cancer
Publikationsdatum
18.12.2018
Erschienen in
Clinical and Translational Oncology / Ausgabe 7/2019
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-018-02005-7

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