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Immune checkpoint inhibitor for advanced or recurrent non-small cell lung cancer patients with poor performance status
abstracts
Annals of Oncology
P3 071
Immune checkpoint inhibitor for advanced or recurrent non-small cell lung cancer patients with poor performance status
Junji Koyama1, Tomoki Kimura1, Hajime Oi1, Yasuhiko Yamano1, Toshiki Yokoyama1, Toshiaki Matsuda1, Kensuke Kataoka1, Reiko Matsuzawa2, Jun Fukihara2, Koji Sakamoto2, Masahiro Morise2, Naozumi Hashimoto2, Yasuhiro Kondoh1, Yoshinori Hasegawa2 1 Department of Respiratory Medicine and Allergy, Tosei General Hospital, 2Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Background: The efficacy and safety of immune checkpoint inhibitor (ICI) for advanced or recurrent non-small cell lung cancer (NSCLC) with poor performance status (PS) is unknown. Methods: A multicenter retrospective study was conducted for patients with advanced or recurrent NSCLC with PS 2 who received ICI between January 2016 and September 2018. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and occurrence of immune-related adverse event (irAE) were assessed for all participants. Results: A total of 20 patients (median age: 61 years; age range: 44-80 years; male/ female ratio: 10/10) were included with the following demographics: PS2/3: 14/6; current or former/never smoker ratio: 15/5; squamous/non-squamous cell carcinoma cases: 2/18; PD-L1 50%/1%-49%/0%/unknown: 6/2/1/11; nivolumab/pembrolizumab/atezolizumab: 11/5/4; 1st/2nd/3rd or subsequent line: 5/4/11. For the overall population, ORR, DCR, median PFS, and median OS were 5%, 20%, 0.8 months [95% confidence interval (CI), 0.5-1.8], and 2.5 months (95% CI, 1.3-4.3), respectively. Even for the population with PD-L1 50%, ORR, DCR, median PFS, and median OS were 0%, 17%, 0.9 months (95% CI, 0.2-NA), and 3.2 months (95% CI, 0.8-NA), respectively. IrAE was recorded in 5 cases; the most common being fever (n ¼ 2) and included pruritus, cholangitis, and pneumonitis (n ¼ 1 each). In the case with cholangitis, ICI was discontinued due to irAE. Conclusion: The efficacy of ICI for advanced or recurrent NSCLC patients with PS 2 was suggested to be poor, including the participant population with PD-L1 50%.
P3 073
Clinical outcome of early development of pneumonitis in nonsmall cell lung cancer patients treated with durvalumab
Akira Sugimoto1, Yoshitaka Zenke1, Hidehiro Hojo2, Masaki Nakamura2, Hibiki Udagawa1, Keisuke Kirita1, Takaya Ikeda1, Singo Matsumoto1, Kiyotaka Yoh1, Seiji Niho1, Tetsuo Akimoto2, Koichi Goto1 1 Department of Thoracic Oncology, National Cancer Center Hospital East, 2Department of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East Background: Treatment-related pneumonitis typically occurs 4 weeks later following durvalumab consolidation therapy in patients with non-small cell lung cancer (NSCLC). However, the clinical outcome of early development of pneumonitis within 4 weeks following durvalumab consolidation therapy remain unclear. We retrospectively evaluate clinical outcome of early development of pneumonitis in NSCLC patients who had received durvalumab. Methods: We retrospectively reviewed all consecutive cases of NSCLC patients who had received durvalumab after chemoradiotherapy in our hospital from June 2018 to January 2019. The clinical characteristics of the patients who had developed pneumonitis were reviewed and compared between occurred pneumonitis within 4 weeks and 4weeks later. Results: We identified 28 patients who had received durvalumab. The development of pneumonitis of any grade was 79% (n ¼ 22). The median times to the occurrence of pneumonitis were 4 weeks (range: 2-8). Among the 22 patients who had developed
Volume 30 | Supplement 6 | October 2019
pneumonitis, 14 patients (64%) occurred pneumonitis within 4 weeks (early group), while the remaining 8 patients (36%) occurred pneumonitis 4 weeks later (non-early group). Clinical characteristics in predictive for pneumonitis risk were not significantly different in both groups. The development of grade 2 or higher pneumonitis was 32% (n ¼ 7) and 6 out of 7 patients (86%) were in early group. The patients who discontinued durvalumab due to pneumonitis were observed higher in early group than nonearly group (42% vs. 13%). In early group, all patients resumed durvalumab by the management with systemic corticosteroids. Only 1 patients (5%) definite terminated durvalumab due to grade 3 pneumonitis in non-early group. Conclusion: Grade 2 or higher pneumonitis often developed within 4weeks following durvalumab consolidation therapy. Almost patients could continue durvalumab without definite termination with appropriate supportive care in early development of pneumonitis.
P3 074
Efficacy of immune checkpoint inhibitors in driver mutationpositive non-small lung cancer patients
Kazuhiro Shiraishi1, Keiji Sugiyama1, Mariko Sato1, Atsushi Torii2, Arisa Yamada2, Akane Ishida2, Fumie Shigemasu2, Kazuki Nozawa1, Hideyuki Niwa2, Yuko Ise2, Yoriko Funahashi1, Masashi Nakahata2, Saori Oka2, Yoshihito Kogure1,2, Chiyoe Kitagawa1,2, Masahide Oki2, Hideo Saka1,2 1 Department of Medical Oncology, Nagoya Medical Center, 2Department of Respiratory Medicine, Nagoya Medical Center Background: Recent studies have reported that immune checkpoint inhibitors (ICI) are ineffective in non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) receptor. Methods: This study was designed as a single-institute, retrospective chart review. We reviewed 103 NSCLC patients treated with an ICI regimen (Nivolumab, Pembrolizumab, and Atezolizumab) between January 2009 and November 2018 at Nagoya Medical Center. The inclusion criteria were: metastatic or recurrent NSCLC with or without a driver oncogene, normal organ function, and ECOG Performance Status (PS) 0-2. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS, calculated from the first day of ICI administration) and overall response rate (ORR) Results: Eighty-two pts (median age, 69 years; range, 33-88) met the inclusion criteria. Among them, 13 pts had driver oncogenes (mtþ) (EGFR 12, ALK 1), and 69 pts did not have driver oncogenes (mt-). ECOG-PS was 0, 1, and 2 in 27, 40, and 15 pts, respectively. Median number of regimen prior to ICI treatment was 2 (range 1-8, including EGFR-tyrosine kinase inhibitors (EGFR-TKI) and ALK inhibitors) in mtþ pts and 1 (range 0-11) in mt- pts. Programmed cell death ligand 1 (PD-L1) expression <50%, 50% and unknown was seen in 5, 2, and 6 mtþ pts and 20, 27, and 22 mt- pts, respectively. Median PFS (mPFS) in mtþ vs. mt- pts was 6 weeks (95% CI, 1.8-14) vs. 22 weeks (95% CI, 11-42); p ¼ 0.0016. Median OS (mOS) in mtþ vs. mt- pts was 12 months (95% CI, 9-29) vs. 16 months (95% CI, 6-18); p ¼ 0.237. The mPFS of mt- pts according to PD-L1 expression was: PD-L1 <50%, 11 weeks (95% CI, 5.2-20); PD-L1 50%, 55 weeks (95% CI, 7-NA). ORR in mtþ and mt- patients were 0% and 65%, respectively. Conclusions: This study showed that PFS following ICI therapy is longer in mt- than mtþ pts, suggesting that ICI is less efficacious in mtþ than mt- NSCLC pts.
P3 076
Retrospective study of immune-related adverse events in NSCLC patients treated with PD-1 inhibitors
Aya Otsubo1, Takeshi Ota2, Masaaki Okajima3, Hiroshi Tanaka4, Takashi Ishida1, Akira Iwashima5, Satoshi Watanabe6, Kazuhiro Sato7, Naoya Matsumoto8, Takao Miyabayashi9, Masaki Terada3, Ko Sato10, Daisuke Ishikawa11, Yoshinari Tanabe2, Hirohisa Yoshizawa12, Toshiaki Kikuchi6 1 Department of Internal Medicine,Niigata Prefectural Central Hospital, 2Department of Internal Medicine,Niigata Prefectural Shibata Hospital, 3Department of Respiratory Medicine,Saiseikai Niigata Daini Hospital, 4Department of Internal Medicine,Niigata Cancer Center Hospital, 5Department of Respiratory Medicine,Nagaoka Chuo General Hospital, 6Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 7Department of Respiratory Medicine,Nagaoka Red Cross Hospital, 8Department of Respiratory Medicine,NishiNiigata Chuo National Hospital, 9Department of Respiratory Medicine,Niigata City General Hospital, 10Department of Respiratory Medicine,Tsuruoka Municipal Shonai Hospital, 11Department of Respiratory Medicine,Sado General Hospital, 12Department of Respiratory Medicine,Niigata Medical Center Background: Recent studies have reported that immune-checkpoint inhibitors (ICIs) cause various immune-related adverse events (irAEs) and irAEs are associated with antitumor effects of ICIs. However, it remains unclear whether the incidence of irAEs was associated with types of PD-1 inhibitors and treatment lines. Methods: We retrospectively evaluated data of advanced or recurrent NSCLC patients treated in 1st to 3rd line with PD-1 inhibitors at Niigata Lung Cancer Treatment Group between January 2016 and October 2017. Results: Of 231 patients who received anti-PD-1 therapies, 176 patients received nivolumab and 55 patients received pembrolizumab, and 63 patients (36%) developed
doi:10.1093/annonc/mdz343 | vi141
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.108/5583101 by guest on 25 October 2019
2018 as the primary treatment in EGFR mutation positive non-small cell lung cancer. In this study, we compared the safety of osimertinib administration after the primary and secondary treatments. Method: 73 patients with non-small cell lung cancer who received osimertinib from March 2016 to February 2019 were investigated after the follow-up and the adverse events were compared between the first-line treatment (1stOsi) group and the previously treated T790M positive (2ndOsi) group. Adverse events were assessed with CTCAE v4.0. Result: The median age of the 1stOsi group (n ¼ 23) was 74 years, male: 6 (26%) / female: 17 (74%), the median age of 2ndOsi group (n ¼ 50) was 70 years, male: 15 (30%) / female 35 (70%). When comparing 1stOsi group with 2ndOsi group, significant difference was found between stomatitis [8 (35%) vs 7 (14%), P ¼ 0.04], fatigue [0 (0%) vs 8 (16%), P ¼ 0.04], thrombocytopenia [6 (26%) vs 26 (52%), P ¼ 0.04], anemia [7 (30%) vs 29 (58%), P ¼ 0.03]. Significant difference was observed in adverse events of Grade 3 tended to be more frequent in 2ndOsi group than in 1stOsi group (30% vs 52%, P ¼ 0.08). Discussion: From the results, it was found that the administration of osimertinib as the primary treatment showed more frequent rash and stomatitis oral, and the frequency of bone marrow suppression was less frequent as compared with the secondary treatment. In addition, no new adverse event profile is developed and the extent is also mild, so we can deal with the conventional patient education.
Annals of Oncology
P3 071
Immune checkpoint inhibitor for advanced or recurrent non-small cell lung cancer patients with poor performance status
Junji Koyama1, Tomoki Kimura1, Hajime Oi1, Yasuhiko Yamano1, Toshiki Yokoyama1, Toshiaki Matsuda1, Kensuke Kataoka1, Reiko Matsuzawa2, Jun Fukihara2, Koji Sakamoto2, Masahiro Morise2, Naozumi Hashimoto2, Yasuhiro Kondoh1, Yoshinori Hasegawa2 1 Department of Respiratory Medicine and Allergy, Tosei General Hospital, 2Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Background: The efficacy and safety of immune checkpoint inhibitor (ICI) for advanced or recurrent non-small cell lung cancer (NSCLC) with poor performance status (PS) is unknown. Methods: A multicenter retrospective study was conducted for patients with advanced or recurrent NSCLC with PS 2 who received ICI between January 2016 and September 2018. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and occurrence of immune-related adverse event (irAE) were assessed for all participants. Results: A total of 20 patients (median age: 61 years; age range: 44-80 years; male/ female ratio: 10/10) were included with the following demographics: PS2/3: 14/6; current or former/never smoker ratio: 15/5; squamous/non-squamous cell carcinoma cases: 2/18; PD-L1 50%/1%-49%/0%/unknown: 6/2/1/11; nivolumab/pembrolizumab/atezolizumab: 11/5/4; 1st/2nd/3rd or subsequent line: 5/4/11. For the overall population, ORR, DCR, median PFS, and median OS were 5%, 20%, 0.8 months [95% confidence interval (CI), 0.5-1.8], and 2.5 months (95% CI, 1.3-4.3), respectively. Even for the population with PD-L1 50%, ORR, DCR, median PFS, and median OS were 0%, 17%, 0.9 months (95% CI, 0.2-NA), and 3.2 months (95% CI, 0.8-NA), respectively. IrAE was recorded in 5 cases; the most common being fever (n ¼ 2) and included pruritus, cholangitis, and pneumonitis (n ¼ 1 each). In the case with cholangitis, ICI was discontinued due to irAE. Conclusion: The efficacy of ICI for advanced or recurrent NSCLC patients with PS 2 was suggested to be poor, including the participant population with PD-L1 50%.
P3 073
Clinical outcome of early development of pneumonitis in nonsmall cell lung cancer patients treated with durvalumab
Akira Sugimoto1, Yoshitaka Zenke1, Hidehiro Hojo2, Masaki Nakamura2, Hibiki Udagawa1, Keisuke Kirita1, Takaya Ikeda1, Singo Matsumoto1, Kiyotaka Yoh1, Seiji Niho1, Tetsuo Akimoto2, Koichi Goto1 1 Department of Thoracic Oncology, National Cancer Center Hospital East, 2Department of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East Background: Treatment-related pneumonitis typically occurs 4 weeks later following durvalumab consolidation therapy in patients with non-small cell lung cancer (NSCLC). However, the clinical outcome of early development of pneumonitis within 4 weeks following durvalumab consolidation therapy remain unclear. We retrospectively evaluate clinical outcome of early development of pneumonitis in NSCLC patients who had received durvalumab. Methods: We retrospectively reviewed all consecutive cases of NSCLC patients who had received durvalumab after chemoradiotherapy in our hospital from June 2018 to January 2019. The clinical characteristics of the patients who had developed pneumonitis were reviewed and compared between occurred pneumonitis within 4 weeks and 4weeks later. Results: We identified 28 patients who had received durvalumab. The development of pneumonitis of any grade was 79% (n ¼ 22). The median times to the occurrence of pneumonitis were 4 weeks (range: 2-8). Among the 22 patients who had developed
Volume 30 | Supplement 6 | October 2019
pneumonitis, 14 patients (64%) occurred pneumonitis within 4 weeks (early group), while the remaining 8 patients (36%) occurred pneumonitis 4 weeks later (non-early group). Clinical characteristics in predictive for pneumonitis risk were not significantly different in both groups. The development of grade 2 or higher pneumonitis was 32% (n ¼ 7) and 6 out of 7 patients (86%) were in early group. The patients who discontinued durvalumab due to pneumonitis were observed higher in early group than nonearly group (42% vs. 13%). In early group, all patients resumed durvalumab by the management with systemic corticosteroids. Only 1 patients (5%) definite terminated durvalumab due to grade 3 pneumonitis in non-early group. Conclusion: Grade 2 or higher pneumonitis often developed within 4weeks following durvalumab consolidation therapy. Almost patients could continue durvalumab without definite termination with appropriate supportive care in early development of pneumonitis.
P3 074
Efficacy of immune checkpoint inhibitors in driver mutationpositive non-small lung cancer patients
Kazuhiro Shiraishi1, Keiji Sugiyama1, Mariko Sato1, Atsushi Torii2, Arisa Yamada2, Akane Ishida2, Fumie Shigemasu2, Kazuki Nozawa1, Hideyuki Niwa2, Yuko Ise2, Yoriko Funahashi1, Masashi Nakahata2, Saori Oka2, Yoshihito Kogure1,2, Chiyoe Kitagawa1,2, Masahide Oki2, Hideo Saka1,2 1 Department of Medical Oncology, Nagoya Medical Center, 2Department of Respiratory Medicine, Nagoya Medical Center Background: Recent studies have reported that immune checkpoint inhibitors (ICI) are ineffective in non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) receptor. Methods: This study was designed as a single-institute, retrospective chart review. We reviewed 103 NSCLC patients treated with an ICI regimen (Nivolumab, Pembrolizumab, and Atezolizumab) between January 2009 and November 2018 at Nagoya Medical Center. The inclusion criteria were: metastatic or recurrent NSCLC with or without a driver oncogene, normal organ function, and ECOG Performance Status (PS) 0-2. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS, calculated from the first day of ICI administration) and overall response rate (ORR) Results: Eighty-two pts (median age, 69 years; range, 33-88) met the inclusion criteria. Among them, 13 pts had driver oncogenes (mtþ) (EGFR 12, ALK 1), and 69 pts did not have driver oncogenes (mt-). ECOG-PS was 0, 1, and 2 in 27, 40, and 15 pts, respectively. Median number of regimen prior to ICI treatment was 2 (range 1-8, including EGFR-tyrosine kinase inhibitors (EGFR-TKI) and ALK inhibitors) in mtþ pts and 1 (range 0-11) in mt- pts. Programmed cell death ligand 1 (PD-L1) expression <50%, 50% and unknown was seen in 5, 2, and 6 mtþ pts and 20, 27, and 22 mt- pts, respectively. Median PFS (mPFS) in mtþ vs. mt- pts was 6 weeks (95% CI, 1.8-14) vs. 22 weeks (95% CI, 11-42); p ¼ 0.0016. Median OS (mOS) in mtþ vs. mt- pts was 12 months (95% CI, 9-29) vs. 16 months (95% CI, 6-18); p ¼ 0.237. The mPFS of mt- pts according to PD-L1 expression was: PD-L1 <50%, 11 weeks (95% CI, 5.2-20); PD-L1 50%, 55 weeks (95% CI, 7-NA). ORR in mtþ and mt- patients were 0% and 65%, respectively. Conclusions: This study showed that PFS following ICI therapy is longer in mt- than mtþ pts, suggesting that ICI is less efficacious in mtþ than mt- NSCLC pts.
P3 076
Retrospective study of immune-related adverse events in NSCLC patients treated with PD-1 inhibitors
Aya Otsubo1, Takeshi Ota2, Masaaki Okajima3, Hiroshi Tanaka4, Takashi Ishida1, Akira Iwashima5, Satoshi Watanabe6, Kazuhiro Sato7, Naoya Matsumoto8, Takao Miyabayashi9, Masaki Terada3, Ko Sato10, Daisuke Ishikawa11, Yoshinari Tanabe2, Hirohisa Yoshizawa12, Toshiaki Kikuchi6 1 Department of Internal Medicine,Niigata Prefectural Central Hospital, 2Department of Internal Medicine,Niigata Prefectural Shibata Hospital, 3Department of Respiratory Medicine,Saiseikai Niigata Daini Hospital, 4Department of Internal Medicine,Niigata Cancer Center Hospital, 5Department of Respiratory Medicine,Nagaoka Chuo General Hospital, 6Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 7Department of Respiratory Medicine,Nagaoka Red Cross Hospital, 8Department of Respiratory Medicine,NishiNiigata Chuo National Hospital, 9Department of Respiratory Medicine,Niigata City General Hospital, 10Department of Respiratory Medicine,Tsuruoka Municipal Shonai Hospital, 11Department of Respiratory Medicine,Sado General Hospital, 12Department of Respiratory Medicine,Niigata Medical Center Background: Recent studies have reported that immune-checkpoint inhibitors (ICIs) cause various immune-related adverse events (irAEs) and irAEs are associated with antitumor effects of ICIs. However, it remains unclear whether the incidence of irAEs was associated with types of PD-1 inhibitors and treatment lines. Methods: We retrospectively evaluated data of advanced or recurrent NSCLC patients treated in 1st to 3rd line with PD-1 inhibitors at Niigata Lung Cancer Treatment Group between January 2016 and October 2017. Results: Of 231 patients who received anti-PD-1 therapies, 176 patients received nivolumab and 55 patients received pembrolizumab, and 63 patients (36%) developed
doi:10.1093/annonc/mdz343 | vi141
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.108/5583101 by guest on 25 October 2019
2018 as the primary treatment in EGFR mutation positive non-small cell lung cancer. In this study, we compared the safety of osimertinib administration after the primary and secondary treatments. Method: 73 patients with non-small cell lung cancer who received osimertinib from March 2016 to February 2019 were investigated after the follow-up and the adverse events were compared between the first-line treatment (1stOsi) group and the previously treated T790M positive (2ndOsi) group. Adverse events were assessed with CTCAE v4.0. Result: The median age of the 1stOsi group (n ¼ 23) was 74 years, male: 6 (26%) / female: 17 (74%), the median age of 2ndOsi group (n ¼ 50) was 70 years, male: 15 (30%) / female 35 (70%). When comparing 1stOsi group with 2ndOsi group, significant difference was found between stomatitis [8 (35%) vs 7 (14%), P ¼ 0.04], fatigue [0 (0%) vs 8 (16%), P ¼ 0.04], thrombocytopenia [6 (26%) vs 26 (52%), P ¼ 0.04], anemia [7 (30%) vs 29 (58%), P ¼ 0.03]. Significant difference was observed in adverse events of Grade 3 tended to be more frequent in 2ndOsi group than in 1stOsi group (30% vs 52%, P ¼ 0.08). Discussion: From the results, it was found that the administration of osimertinib as the primary treatment showed more frequent rash and stomatitis oral, and the frequency of bone marrow suppression was less frequent as compared with the secondary treatment. In addition, no new adverse event profile is developed and the extent is also mild, so we can deal with the conventional patient education.