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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 8/2020

01-08-2020 | SCLC | Original Article

Outcomes with immune checkpoint inhibitors for relapsed small-cell lung cancer in a Swiss cohort

Authors: Sabine Schmid, Laetitia A. Mauti, Alex Friedlaender, Veronika Blum, Sacha I. Rothschild, Hasna Bouchaab, Patrizia Frösch, Christian Britschgi, David König, Luciano Wannesson, Wolf-Dieter Janthur, Sämi Schär, Izadora Demmer, Alfredo Addeo, Wolfram Jochum, Martin Früh

Published in: Cancer Immunology, Immunotherapy | Issue 8/2020

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Abstract

Objectives

Early clinical trials showed promising outcomes with immune-checkpoint inhibitors (ICI) in a subset of patients with relapsed small-cell lung carcinoma (SCLC). The aim of this retrospective analysis was to assess the efficacy and safety of ICI for relapsed SCLC in a real-world patient population.

Methods

Nine cancer centres in Switzerland contributed data to this cohort. Responses were assessed by the local investigators using standard RECIST v1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analysed by the Kaplan–Meier method. Associations between potential predictive markers and survival endpoints were probed by Cox proportional hazards.

Results

Forty-five patients were included in the analysis. Median age was 63 years, 73% were males and 18% had an ECOG performance status (PS) ≥ 2. ICIs were given as second-line treatment in 60%. Twenty-four patients (53%) received ipilimumab with nivolumab. Twenty-eight patients (62%) had undergone irradiation (RT) prior to or during ICI. Overall response rate (ORR) was 29% and median PFS and OS were 2.3 and 6.5 months, respectively. Median duration of response was 9 months (95% CI 2.8–NA). Five patients maintained their response for > 6 months, all of them receiving combination treatment. There were no new safety signals.

Conclusion

This is the first report of “real-world” data on ICI in relapsed SCLC also including patients with poor PS. Promising durable responses were observed. No biological prognostic marker could be identified.
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Literature
1.
Pujol JL, Carestia L, Daures JP (2000) Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer 83:8–15CrossRef
2.
Mascaux C, Paesmans M, Berghmans T et al (2000) A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis. Lung Cancer 30:23–36CrossRef
3.
Horn L, Mansfield AS, Szczęsna A et al (2018) First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 379:2220–2229CrossRef
4.
Paz-Ares L (2019) PL02.11 Overall survival with durvalumab plus etoposide-platinum in first-line extensive-stage SCLC: results from the CASPIAN study. J Thoracic Oncol 14:S7–S8CrossRef
5.
Foster NR, Qi Y, Shi Q et al (2011) Tumor response and progression-free survival as potential surrogate endpoints for overall survival in extensive stage small-cell lung cancer: findings on the basis of North Central Cancer Treatment Group trials. Cancer 117:1262–1271CrossRef
6.
O’Brien ME, Ciuleanu TE, Tsekov H et al (2006) Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 24:5441–5447CrossRef
7.
Eckardt JR, von Pawel J, Pujol JL et al (2007) Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 25:2086–2092CrossRef
8.
von Pawel J, Schiller JH, Shepherd FA et al (1999) Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17:658–667CrossRef
9.
Antonia SJ, Lopez-Martin JA, Bendell J et al (2016) Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 17:883–895CrossRef
10.
Ott PA, Elez E, Hiret S et al (2017) Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 Study. J Clin Oncol 35:3823–3829CrossRef
11.
Chung H, Lopez-Martin J, Kao S et al (2018) Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158. J Clin Oncol 36:8506CrossRef
12.
Ready N, Farago AF, de Braud F et al (2019) Third-line nivolumab monotherapy in recurrent SCLC: CheckMate 032. J Thorac Oncol 14:237–244CrossRef
13.
Reck M, Vincente D, Ciuleanu T et al (2018) LBA5—efficacy and safety of nivolumab (nivo) monotherapy versus chemotherapy (chemo) in recurrent small cell lung cancer (SCLC): results from CheckMate 331. Ann Oncol 29:x39–x43CrossRef
14.
Pujol JL, Greillier L, Audigier-Valette C et al (2019) A randomized non-comparative phase 2 study of anti-programmed cell death-ligand 1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: results from the IFCT-1603 trial. J Thorac Oncol 14:903–913CrossRef
15.
Chung H, Piha-Paul S, Lopez-Martin J et al (2019) CT073—Pembrolizumab after two or more lines of prior therapy in patients with advanced small-cell lung cancer (SCLC): results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol 15(4):618–627CrossRef
16.
Goldman JW, Dowlati a, Antonia SJ et al (2018) Safety and antitumor activity of durvalumab monotherapy in patients with pretreated extensive disease small-cell lung cancer (ED-SCLC). J Clin Onco 36(15_suppl):8518–8518
17.
Cho D, Mahipal A, Dowlati A et al (2018) Safety and clinical activity of durvalumab in combination with tremelimumab in extensive disease small-cell lung cancer (ED-SCLC). J Clin Oncol 36(15_suppl):8517–8517
18.
Hellmann MD, Ott PA, Zugazagoitia J et al (2017) Nivolumab (nivo) ± ipilimumab (ipi) in advanced small-cell lung cancer (SCLC): First report of a randomized expansion cohort from CheckMate 032. J Clin Oncol 35(15_suppl):8503–8503
19.
Lai WCV, Rizvi H, Egger JV et al (2019) Real-world experience and molecular features of response to immune checkpoint blockade in patients with recurrent small cell lung cancer. J Clin Oncol 37(15_suppl):8556–855
20.
Graus F, Dalmou J, Rene R et al (1997) Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival. J Clin Oncol 15:2866–2872
21.
Darnell RB and Posner JB (2003) Paraneoplastic syndromes involving the nervous system. N Engl J Med 349:1543–1554
22.
Owonikoko TK, Kim HR, Govindan R et al (2019) Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study. Ann Oncol 30 (Supplement 2):ii77–ii80
23.
Shaverdian N, Lisberg AE, Bornakyan K et al (2017) Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol 18(7):895–903
24.
Diem S, Kasenda B, Spain L et al (2016) Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Br J Cancer 114:256–261CrossRef
25.
Mok TSK, Wu YL, Kudaba I et al (2019) 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 393:1819–1830CrossRef
26.
Fehrenbacher L, Spira A, Ballinger M et al (2016) Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387:1837–1846CrossRef
27.
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 387:1540–1550CrossRef
28.
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 373:1627–1639CrossRef
29.
Hellmann MD, Ciuleanu TE, Pluzanski A et al (2018) Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 378:2093–2104CrossRef
30.
Sabari JK, Leonardi GC, Shu CA et al (2018) PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers. Ann Oncol 29:2085–2091CrossRef
31.
Goodman AM, Kato S, Bazhenova L et al (2017) Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther 16:2598–2608CrossRef
32.
Chan TA, Yarchoan M, Jaffee E et al (2019) Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol 30:44–56CrossRef
33.
Daud AI, Loo K, Pauli ML et al (2016) Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest 126:3447–3452CrossRef
34.
Schmid S, Fruh M (2018) Immune checkpoint inhibitors and small cell lung cancer: what’s new? J Thorac Dis 10:S1503–S1508CrossRef
35.
Schultheis AM, Scheel AH, Ozretic L et al (2015) PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer 51:421–426CrossRef
36.
George J, Saito M, Tsuta K et al (2017) Genomic amplification of CD274 (PD-L1) in small-cell lung cancer. Clin Cancer Res 23:1220–1226CrossRef
37.
Yasuda Y, Ozasa H, Kim YH (2018) PD-L1 expression in small cell lung cancer. J Thorac Oncol 13:e40–e41CrossRef
38.
Ricciuti B, Kravets S, Dahlberg SE et al (2019) Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer. J Immunother Cancer 7:87CrossRef
39.
Ready NE, Ott PA, Hellmann MD et al (2019) Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol 15(3):426–435
40.
Hellmann MD, Callahan MK, Awad MM et al (2018) Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell 33:853–861CrossRef
Metadata
Title
Outcomes with immune checkpoint inhibitors for relapsed small-cell lung cancer in a Swiss cohort
Authors
Sabine Schmid
Laetitia A. Mauti
Alex Friedlaender
Veronika Blum
Sacha I. Rothschild
Hasna Bouchaab
Patrizia Frösch
Christian Britschgi
David König
Luciano Wannesson
Wolf-Dieter Janthur
Sämi Schär
Izadora Demmer
Alfredo Addeo
Wolfram Jochum
Martin Früh
Publication date
01-08-2020
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 8/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02565-0

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