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Published in: Drugs in R&D 4/2021

Open Access 01-12-2021 | Metastasis | Original Research Article

Dissociated Responses in Patients with Metastatic Solid Tumors Treated with Immunotherapy

Authors: Pauline Vaflard, Xavier Paoletti, Vincent Servois, Patricia Tresca, Elvire Pons-Tostivint, Marie-Paule Sablin, Francesco Ricci, Delphine Loirat, Ségolène Hescot, Nouritza Torossian, Diana Bello Roufai, Maud Kamal, Edith Borcoman, Christophe Le Tourneau

Published in: Drugs in R&D | Issue 4/2021

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Abstract

Background

Immune checkpoint inhibitors have been demonstrated to improve overall survival. Atypical patterns of response have been reported, including dissociated response (DR). We evaluated the prevalence of DR.

Patients and methods

Patients had to have a baseline computed tomography (CT) scan and at least one follow-up CT scan and two target lesions (TLs). Three types of DR were evaluated using RECIST1.1: DR1, defined as at least one progressive and one responding TL; DR2, defined as at least one progressive and one stable TL; and DR3, defined as at least one stable and one responding TL.

Results

A total of 1244 measurements of 272 TLs were performed in 100 patients. Forty-nine out of the 272 TLs (18%) had received old or recent radiotherapy, and 42 (15%) had been biopsied. An objective response was observed in 22 patients (22%) and on 52 TLs (19%). DR1 were observed in 8% of patients. At the tumor measurement level, the response rate was lower in the case of prior radiotherapy (29% vs 34%, p = 0.01) and higher in the case of prior biopsy (40% vs 32%, p = 0.02).

Conclusions

A DR was observed in 8% of patients. Response rate was lower in the case of prior radiotherapy and higher in the case of prior biopsy.
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Literature
1.
go back to reference Salama AKS, Postow MA, Salama JK. Irradiation and immunotherapy: from concept to the clinic. Cancer. 2016;122(11):1659–71.CrossRef Salama AKS, Postow MA, Salama JK. Irradiation and immunotherapy: from concept to the clinic. Cancer. 2016;122(11):1659–71.CrossRef
2.
go back to reference Grossman SA, Ellsworth S, Campian J, et al. Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Cancer Netw JNCCN. 2015;13(10):1225–31.CrossRef Grossman SA, Ellsworth S, Campian J, et al. Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Cancer Netw JNCCN. 2015;13(10):1225–31.CrossRef
3.
go back to reference Wirsdörfer F, de Leve S, Jendrossek V. Combining radiotherapy and immunotherapy in lung cancer: can we expect limitations due to altered normal tissue toxicity? Int J Mol Sci. 2018;20:24.CrossRef Wirsdörfer F, de Leve S, Jendrossek V. Combining radiotherapy and immunotherapy in lung cancer: can we expect limitations due to altered normal tissue toxicity? Int J Mol Sci. 2018;20:24.CrossRef
4.
go back to reference Straub JM, New J, Hamilton CD, et al. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol. 2015;141(11):1985–94.CrossRef Straub JM, New J, Hamilton CD, et al. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol. 2015;141(11):1985–94.CrossRef
5.
go back to reference Borcoman E, Kanjanapan Y, Champiat S, et al. Novel patterns of response under immunotherapy. Ann Oncol. 2019;30(3):385–96.CrossRef Borcoman E, Kanjanapan Y, Champiat S, et al. Novel patterns of response under immunotherapy. Ann Oncol. 2019;30(3):385–96.CrossRef
6.
go back to reference Tazdait M, Mezquita L, Lahmar J, et al. Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: comparison of RECIST 11, irRECIST and iRECIST criteria. Eur J Cancer. 2018;88:38–47.CrossRef Tazdait M, Mezquita L, Lahmar J, et al. Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: comparison of RECIST 11, irRECIST and iRECIST criteria. Eur J Cancer. 2018;88:38–47.CrossRef
7.
go back to reference Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020.CrossRef Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020.CrossRef
8.
go back to reference Schwartz LH, Seymour L, Litière S, et al. RECIST 1.1—standardisation and disease-specific adaptations: perspectives from the RECIST Working Group. Eur J Cancer. 2016;62(Supplement C):138–45.CrossRef Schwartz LH, Seymour L, Litière S, et al. RECIST 1.1—standardisation and disease-specific adaptations: perspectives from the RECIST Working Group. Eur J Cancer. 2016;62(Supplement C):138–45.CrossRef
9.
go back to reference Pons-Tostivint E, Latouche A, Vaflard P, et al. Comparative analysis of durable responses on immune checkpoint inhibitors versus other systemic therapies: a pooled analysis of phase III trials. JCO Precis Oncol. 2019;3:1–10. Pons-Tostivint E, Latouche A, Vaflard P, et al. Comparative analysis of durable responses on immune checkpoint inhibitors versus other systemic therapies: a pooled analysis of phase III trials. JCO Precis Oncol. 2019;3:1–10.
10.
go back to reference Tumeh PC, Hellmann MD, Hamid O, et al. Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res. 2017;5(5):417–24.CrossRef Tumeh PC, Hellmann MD, Hamid O, et al. Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res. 2017;5(5):417–24.CrossRef
11.
go back to reference Takamori S, Takada K, Tagawa T, et al. Differences in PD-L1 expression on tumor and immune cells between lung metastases and corresponding primary tumors. Surg Oncol. 2018;27(4):637–41.CrossRef Takamori S, Takada K, Tagawa T, et al. Differences in PD-L1 expression on tumor and immune cells between lung metastases and corresponding primary tumors. Surg Oncol. 2018;27(4):637–41.CrossRef
12.
go back to reference Mazzolini G, Ochoa MC, Morales-Kastresana A, et al. The liver, liver metastasis and liver cancer: a special case for immunotherapy with cytokines and immunostimulatory monoclonal antibodies. Immunotherapy. 2012;4(11):1081–5.CrossRef Mazzolini G, Ochoa MC, Morales-Kastresana A, et al. The liver, liver metastasis and liver cancer: a special case for immunotherapy with cytokines and immunostimulatory monoclonal antibodies. Immunotherapy. 2012;4(11):1081–5.CrossRef
13.
go back to reference Gasteiger G, Fan X, Dikiy S, et al. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science. 2015;350(6263):981–5.CrossRef Gasteiger G, Fan X, Dikiy S, et al. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science. 2015;350(6263):981–5.CrossRef
14.
go back to reference Ott PA, Bang Y-J, Piha-Paul SA, et al. T-Cell–inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. J Clin Oncol. 2018;37(4):318–27.CrossRef Ott PA, Bang Y-J, Piha-Paul SA, et al. T-Cell–inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. J Clin Oncol. 2018;37(4):318–27.CrossRef
15.
go back to reference Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105(4):256–65.CrossRef Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105(4):256–65.CrossRef
16.
go back to reference Van Limbergen EJ, De Ruysscher DK, Olivo Pimentel V, et al. Combining radiotherapy with immunotherapy: the past, the present and the future. Br J Radiol. 2017;90(1076):20170157.CrossRef Van Limbergen EJ, De Ruysscher DK, Olivo Pimentel V, et al. Combining radiotherapy with immunotherapy: the past, the present and the future. Br J Radiol. 2017;90(1076):20170157.CrossRef
17.
go back to reference Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.CrossRef Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.CrossRef
18.
go back to reference Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015;12(10):584–96.CrossRef Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015;12(10):584–96.CrossRef
19.
go back to reference Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.CrossRef Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.CrossRef
20.
go back to reference Zhang B, Bowerman NA, Salama JK, et al. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 2007;204(1):49–55.CrossRef Zhang B, Bowerman NA, Salama JK, et al. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 2007;204(1):49–55.CrossRef
21.
go back to reference Marabelle A, Tselikas L, de Baere T, Houot R. Intratumoral immunotherapy: using the tumor as the remedy. Ann Oncol Off J Eur Soc Med Oncol. 2017;28(suppl_12):xii33–43.CrossRef Marabelle A, Tselikas L, de Baere T, Houot R. Intratumoral immunotherapy: using the tumor as the remedy. Ann Oncol Off J Eur Soc Med Oncol. 2017;28(suppl_12):xii33–43.CrossRef
22.
go back to reference Laurie SA, Banerji S, Blais N, et al. Canadian consensus: oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer. Curr Oncol Tor Ont. 2019;26(1):e81–93.CrossRef Laurie SA, Banerji S, Blais N, et al. Canadian consensus: oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer. Curr Oncol Tor Ont. 2019;26(1):e81–93.CrossRef
23.
go back to reference Santini D, Ratta R, Pantano F, et al. Outcome of oligoprogressing metastatic renal cell carcinoma patients treated with locoregional therapy: a multicenter retrospective analysis. Oncotarget. 2017;8(59):100708–16.CrossRef Santini D, Ratta R, Pantano F, et al. Outcome of oligoprogressing metastatic renal cell carcinoma patients treated with locoregional therapy: a multicenter retrospective analysis. Oncotarget. 2017;8(59):100708–16.CrossRef
24.
go back to reference Otake S, Goto T. Stereotactic radiotherapy for oligometastasis. Cancers. 2019;11:133.CrossRef Otake S, Goto T. Stereotactic radiotherapy for oligometastasis. Cancers. 2019;11:133.CrossRef
25.
go back to reference Iyengar P, Kavanagh BD, Wardak Z, et al. 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 Off J Am Soc Clin Oncol. 2014;32(34):3824–30.CrossRef Iyengar P, Kavanagh BD, Wardak Z, et al. 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 Off J Am Soc Clin Oncol. 2014;32(34):3824–30.CrossRef
26.
go back to reference Liniker E, Menzies AM, Kong BY, et al. Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma. Oncoimmunology. 2016;5(9):e1214788.CrossRef Liniker E, Menzies AM, Kong BY, et al. Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma. Oncoimmunology. 2016;5(9):e1214788.CrossRef
27.
go back to reference Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-induced abscopal effect. Cancer Immunol Res. 2015;3(6):610–9.CrossRef Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-induced abscopal effect. Cancer Immunol Res. 2015;3(6):610–9.CrossRef
28.
go back to reference 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 Off J Am Soc Clin Oncol. 2018;36(16):1611–8.CrossRef 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 Off J Am Soc Clin Oncol. 2018;36(16):1611–8.CrossRef
29.
go back to reference Nishino M, Sholl LM, Awad MM, et al. Sarcoid-Like granulomatosis of the lung related to immune-checkpoint inhibitors: distinct clinical and imaging features of a unique immune-related adverse event. Cancer Immunol Res. 2018;6(6):630–5.CrossRef Nishino M, Sholl LM, Awad MM, et al. Sarcoid-Like granulomatosis of the lung related to immune-checkpoint inhibitors: distinct clinical and imaging features of a unique immune-related adverse event. Cancer Immunol Res. 2018;6(6):630–5.CrossRef
30.
go back to reference Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017;18(3):e143–52.CrossRef Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017;18(3):e143–52.CrossRef
Metadata
Title
Dissociated Responses in Patients with Metastatic Solid Tumors Treated with Immunotherapy
Authors
Pauline Vaflard
Xavier Paoletti
Vincent Servois
Patricia Tresca
Elvire Pons-Tostivint
Marie-Paule Sablin
Francesco Ricci
Delphine Loirat
Ségolène Hescot
Nouritza Torossian
Diana Bello Roufai
Maud Kamal
Edith Borcoman
Christophe Le Tourneau
Publication date
01-12-2021
Publisher
Springer International Publishing
Published in
Drugs in R&D / Issue 4/2021
Print ISSN: 1174-5886
Electronic ISSN: 1179-6901
DOI
https://doi.org/10.1007/s40268-021-00362-3

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