Pseudoprogression in Previously Treated Patients with Non-Small Cell Lung Cancer Who Received Nivolumab Monotherapy

Daichi Fujimoto; Hiroshige Yoshioka; Yuki Kataoka; Takeshi Morimoto; Tae Hata; Young Hak Kim; Keisuke Tomii; Tadashi Ishida; Masataka Hirabayashi; Satoshi Hara; Manabu Ishitoko; Yasushi Fukuda; Moon Hee Hwang; Naoki Sakai; Motonari Fukui; Hitoshi Nakaji; Mitsunori Morita; Tadashi Mio; Takehiro Yasuda; Takakazu Sugita; Toyohiro Hirai

doi:10.1016/j.jtho.2018.10.167

Pseudoprogression in Previously Treated Patients with Non-Small Cell Lung Cancer Who Received Nivolumab Monotherapy

J Thorac Oncol. 2019 Mar;14(3):468-474. doi: 10.1016/j.jtho.2018.10.167. Epub 2018 Nov 20.

Authors

Daichi Fujimoto¹, Hiroshige Yoshioka², Yuki Kataoka³, Takeshi Morimoto⁴, Tae Hata², Young Hak Kim⁵, Keisuke Tomii⁶, Tadashi Ishida², Masataka Hirabayashi³, Satoshi Hara⁷, Manabu Ishitoko⁸, Yasushi Fukuda⁹, Moon Hee Hwang¹⁰, Naoki Sakai¹¹, Motonari Fukui¹², Hitoshi Nakaji¹³, Mitsunori Morita¹⁴, Tadashi Mio¹⁵, Takehiro Yasuda¹⁶, Takakazu Sugita¹⁷, Toyohiro Hirai⁵

Affiliations

¹ Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. Electronic address: daichi@kcho.jp.
² Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
³ Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
⁴ Clinical Research Center, Kobe City Medical Center General Hospital, Kobe, Japan; Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan.
⁵ Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan.
⁶ Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
⁷ Department of Respiratory Medicine, Itami City Hospital, Itami, Japan.
⁸ Department of Respiratory Medicine, Shiga General Hospital, Moriyama, Japan.
⁹ Department of Respiratory Medicine, Himeji Medical Center, Himeji, Japan.
¹⁰ Department of Respiratory Medicine, Osaka Red Cross Hospital, Osaka, Japan.
¹¹ Department of Respiratory Medicine, Otsu Red Cross Hospital, Otsu, Japan.
¹² Respiratory Disease Center, Kitano Hospital, The Tazuke-Kofukai Medical Research Institute, Osaka, Japan.
¹³ Department of Respiratory Medicine, Toyooka Public Hospital, Toyooka, Japan.
¹⁴ Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan.
¹⁵ Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
¹⁶ Department of Respiratory Medicine, Tenri Hospital, Nara, Japan.
¹⁷ Department of Respiratory Medicine, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.

PMID: 30468872
DOI: 10.1016/j.jtho.2018.10.167

Abstract

Introduction: Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression.

Methods: We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death.

Results: Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001).

Conclusions: Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression.

Keywords: Immune checkpoint inhibitor; Nivolumab; PD-1; PD-L1; Pseudoprogression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung / drug therapy
Adenocarcinoma of Lung / pathology*
Aged
Antineoplastic Agents, Immunological / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / pathology*
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / pathology*
Disease Progression
Female
Follow-Up Studies
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / pathology*
Male
Middle Aged
Nivolumab / therapeutic use*
Prognosis
Retrospective Studies
Survival Rate

Substances

Antineoplastic Agents, Immunological
Nivolumab