- Email: [email protected]
Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
abstracts (25) were not. The objective response rates were higher in patients with high VFA than in those with low VFA (39% versus 19%; [P ¼ 0.027], respectively). In multivariate analysis, high VSA (hazard ratio: 0.61, 95% confidence interval: 0.40–0.93; [P ¼ 0.022]) and better PS (hazard ratio:0.35, 95% confidence interval: 0.19–0.68; [P ¼ 0.003]) were identified as an independent predictor of longer PFS in patients treated with nivolumab. Conclusions: In patients with advanced NSCLC who received nivolumab, high VFA were independent predictors of nivolumab efficacy. Legal entity responsible for the study: Kobe City Medical Center General Hospital. Funding: Has not received any funding. Disclosure: Y. Sato: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd. D.
1516P
Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
T. Iuchi1, H. Ashinuma2, Y. Yoshida2, S. Mizuno2, J. Hosono1, T. Setoguchi1, Y. Hasegawa1, T. Sakaida1, M. Shingyoji2 1 Neurological Surgery Dept., Chiba Cancer Center Hospital, Chiba, Japan, 2Respirology Dept., Chiba Cancer Center Hospital, Chiba, Japan Background: Immune checkpoint inhibitors (ICPi) have dramatically changed the treatment of non-small cell lung cancer (NSCLC), but the effect of these agents on brain metastases (BM) has not been clearly elucidated. We retrospectively evaluated the effect of ICPi on BM. Methods: NSCLC patients who harbored BM treated with ICPi in out institution were enrolled. History of radiation therapy (RT) to the brain was not included in the selection criteria. The primary endpoint was overall survival after the initiation of ICPi (OS), and the secondary endpoints were duration of ICPi administration, causes of withdrawal, responses of BM, time to the first response of BM, and the incidence of radiation necrosis (RN). Results: 35 NSLC with BM were treated with ICPi: nivolmab in 21, pembrolizumab in 13, and athezolizumab in 1 case. Among these cases, BM were progressive in 25 but stable in 10 cases at the initiation of ICPi. At the time of evaluation, ICPi were already withdrawn in 26 cases and the median administration time was 2.4 (0.5 to 25.9) months. The cause of withdrawal was progression of extracranial lesions in 8, progression of BM in 6, and adverse events or PS deterioration in the others. In competing risk analysis, the times to progression of extra- and intra-cranial lesions were not different. The responses of BM were evaluable in 28 cases: CR in 3, PR in 9, SD in 10 and PD in 6 cases. ICPi had been sequentially administrated after RT in one of the 3 CR and all of the 9 PR cases. The objective response rate was 76.9% after sequential RT/ICPi, but only 13.3% after ICPi alone (P ¼ 0.002). The median time to the first response of BM was 1.0 (0.4 to 3.0) months after RT/ICPi and 1.3 (0.3 to 3.6) months after ICPi alone (n.s.). The median OS was 14.8 (95% CI: 8.8 to 22.7) months after the initiation of ICPi, and majority (90.5%) of the deaths were owing to the progression of extracranial disease. Among the 24 cases with history of RT to the brain, RN was observed in 7 (29.2%) and required necrotomy in 2 cases, even though ICPi could safely be continued after craniotomy in these 2 cases. Conclusions: ICPi alone showed only limited efficacy on BM and were recommended to be administrated sequentially with RT. RN was the major neurological adverse event, and necrotomy was one of the choices to manage RN during ICPi. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1517P
Impact of radiotherapy on efficacy of anti-programmed death 1 (PD1) antibodies in metastatic NSCLC
E. Samuel1, Y.J. So1, A. Hiong2, A. Balasubramanian3, S. Parakh1 Medical Oncology, Monash Health, Melbourne, Australia, 2Internal Medicine, Alfred Health, Melbourne, Australia, 3Medical Oncology, Austin Health, Melbourne, Australia
1
Background: The impact of radiotherapy (RT) on the efficacy and toxicity of immune checkpoint inhibitors in patients (pts) with metastatic non-small cell-lung cancer (NSCLC) is unclear. Methods: We retrospectively identified pts with metastatic NSCLC treated with the anti-programmed death 1 (PD-1) antibodies nivolumab or pembrolizumab between January 2016 and May 2019 at two major oncology centres in Melbourne, Australia. Patient demographics, tumour characteristics, treatment history including radiotherapy (RT) use and toxicity were collected. Disease control rate (DCR), progression free survival (PFS) and overall survival (OS) were analysed and correlated with RT use. Results: 132 pts identified with interim analysis of 54 reported here. Median follow up was 19.4 months. Majority were male (61%) and 87% were smokers. 80% had non-squamous histology, of these 9% had an EGFR mutation. Brain metastases were present in 41%. The median number of cycles of anti-PD1 treatment received was 5 and only 7%
v622 | NSCLC, Metastatic
started anti-PD-1 as first-line therapy. 36% received RT treatment either during or within 3 months of starting anti-PD1 treatment. Of patients that received RT, 74% were treated with extra-thoracic RT. The use of RT before or during anti-PD1 treatment did not result in an increase in high grade immune-related adverse events. The DCR was 35%. The median PFS was 2 months (95% CI 0.5 – 29) and OS 9.7 months (95% CI 1.0 – 31). Pts who received RT had a numerically shorter PFS than those that did not (1.5 vs 2 months, p ¼ 0.668) but numerically longer OS (8.1 vs 7.2 months, p ¼ 0.857). Updated analysis with the full cohort and with longer follow-up will be presented. Conclusions: Radiotherapy did not significantly impact on survival in pts with metastatic NSCLC treated with anti-PD1 therapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1518P
Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real-world data from a European Cohort with focus on subgroups of interest
G. Mountzios1, D. Signorelli2, J. Rey Cobo3, M. Banini4, P. Economopoulou5, G. Lo Russo2, P.T. Baxevanos6, F. Roila4, A. de Toma2, G. Banna7, A. Christopoulou8, B. Jimenez9, H. Linardou10, A. Calles11, D. Galetta12, A. Addeo13, A. Camerini14, P.A. Kosmidis15, M.C. Garassino16, G. Metro17 1 2nd Department of Medical Oncology, Henry Dunant Hospital Center, Athens, Greece, 2 Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 3Oncology, Geneva University Hospital, Geneva, Switzerland, 4S.C. Oncologia, Ospedale Santa Maria della Misericordia, Perugia, Italy, 5Medical Oncology, Attikon University Hospital, Athens, Greece, 6Hematology Dept, Agios Savvas Regional Cancer Hospital, Athens, Greece, 7Medical Oncology, Ospedale Cannizzaro, Catania, Italy, 8 Medical Oncology, Agios Andreas General Hospital of Patras, Athens, Greece, 9Medical Oncology, Hospital HM Sanchinarro, Madrid, Spain, 10Oncology Dept, Metropolitan Hospital, Athens, Greece, 11Medical Oncology, Hospital General Universitario Gregorio Maranon, Madrid, Spain, 12Medical Thoracic Oncology Unit, IRCCS Istituto Oncologico “Giovanni Paolo II”, Bari, Italy, 13Medical Oncology, Hoˆpitaux Universitaires de Gene`ve HUG, Geneva, Switzerland, 14U.O.C. Oncologia, Ospedale "Versilia", Lido Di Camaiore, Italy, 152nd Department of Medical Oncology, Hygeia Hospital, Marousi, Greece, 16 Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy, 17 Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy Background: Real-world data regarding clinical outcomes associated with first-line pembrolizumab (pembro) monotherapy among specific subgroups of NSCLC patients are lacking. Methods: A comprehensive clinicopathological database of patients with NSCLC and PD-L1>50% treated with frontline pembro in 14 centers in Italy, Spain, Greece and Switzerland was retrospectively created. Post-progression outcomes have been previously reported. Clinical outcomes in specific subgroups of interest are presented in the current report. Analysis was performed using the SAS 9.3 software. Multivariate analysis was performed with the Cox regression model. Results: Among 173 eligible patients, median age at diagnosis was 68 years, 65% were male, 88% were current or former smokers, 25% had an ECOG PS > ¼2, histology was 67% adeno, 21% squamous, 20% had brain mets, 15% had liver mets at diagnosis and 28% received steroids at the beginning and/or during treatment. Thirty patients (17.4%) received pembro despite having non-metastatic disease (stage I-IIIC), as deemed medically inoperable or ineligible for definite chemo-radiotherapy. Hazard Ratios for OS, with corresponding 95% CIs and p-values for specific subgroups were as follows: Elderly patients ( >70 years): HR ¼ 0.85 (0.52-1.38), p ¼ 0.51; Brain mets: HR ¼ 1.17 (0.63-2.18), p ¼ 0.63; Stage I-IIIC: HR ¼ 0.56 (0.22-1.39), p ¼ 0.21; PS > ¼2: HR ¼ 1.73 (1.55-1.84), p < 0.0001; Steroid use: HR ¼ 3.27 (1.95-5.50), p < 0.0001; Platinum-based doublet 2nd line : HR ¼ 0.65 (0.29-1.47), p ¼ 0.30. In multivariate analysis, PS and the use of steroids remained independent predictors of survival. Conclusions: Real-world data in a large retrospective cohort of patients with NSCLC and PD-L1>50% indicate that 1) Pembro frontline is also active in inoperable stage IIIIC patients, 2) Elderly patients (>70 years) derive similar survival benefit to younger ones, except from those with PS > ¼2, 3) Steroid use at the beginning and/or during treatment is associated with a three-fold increase in the risk of death. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: G. Mountzios: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca Greece; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Greece; Honoraria (self), Travel / Accommodation / Expenses: Pfizer Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD Hellas; Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis Greece. G. Banna: Advisory / Consultancy: Janssen; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: AstraZeneca; Travel /
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.038/5577832 by guest on 26 October 2019
Fujimoto: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd. K. Hosoya: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.
Annals of Oncology
1516P
Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
T. Iuchi1, H. Ashinuma2, Y. Yoshida2, S. Mizuno2, J. Hosono1, T. Setoguchi1, Y. Hasegawa1, T. Sakaida1, M. Shingyoji2 1 Neurological Surgery Dept., Chiba Cancer Center Hospital, Chiba, Japan, 2Respirology Dept., Chiba Cancer Center Hospital, Chiba, Japan Background: Immune checkpoint inhibitors (ICPi) have dramatically changed the treatment of non-small cell lung cancer (NSCLC), but the effect of these agents on brain metastases (BM) has not been clearly elucidated. We retrospectively evaluated the effect of ICPi on BM. Methods: NSCLC patients who harbored BM treated with ICPi in out institution were enrolled. History of radiation therapy (RT) to the brain was not included in the selection criteria. The primary endpoint was overall survival after the initiation of ICPi (OS), and the secondary endpoints were duration of ICPi administration, causes of withdrawal, responses of BM, time to the first response of BM, and the incidence of radiation necrosis (RN). Results: 35 NSLC with BM were treated with ICPi: nivolmab in 21, pembrolizumab in 13, and athezolizumab in 1 case. Among these cases, BM were progressive in 25 but stable in 10 cases at the initiation of ICPi. At the time of evaluation, ICPi were already withdrawn in 26 cases and the median administration time was 2.4 (0.5 to 25.9) months. The cause of withdrawal was progression of extracranial lesions in 8, progression of BM in 6, and adverse events or PS deterioration in the others. In competing risk analysis, the times to progression of extra- and intra-cranial lesions were not different. The responses of BM were evaluable in 28 cases: CR in 3, PR in 9, SD in 10 and PD in 6 cases. ICPi had been sequentially administrated after RT in one of the 3 CR and all of the 9 PR cases. The objective response rate was 76.9% after sequential RT/ICPi, but only 13.3% after ICPi alone (P ¼ 0.002). The median time to the first response of BM was 1.0 (0.4 to 3.0) months after RT/ICPi and 1.3 (0.3 to 3.6) months after ICPi alone (n.s.). The median OS was 14.8 (95% CI: 8.8 to 22.7) months after the initiation of ICPi, and majority (90.5%) of the deaths were owing to the progression of extracranial disease. Among the 24 cases with history of RT to the brain, RN was observed in 7 (29.2%) and required necrotomy in 2 cases, even though ICPi could safely be continued after craniotomy in these 2 cases. Conclusions: ICPi alone showed only limited efficacy on BM and were recommended to be administrated sequentially with RT. RN was the major neurological adverse event, and necrotomy was one of the choices to manage RN during ICPi. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1517P
Impact of radiotherapy on efficacy of anti-programmed death 1 (PD1) antibodies in metastatic NSCLC
E. Samuel1, Y.J. So1, A. Hiong2, A. Balasubramanian3, S. Parakh1 Medical Oncology, Monash Health, Melbourne, Australia, 2Internal Medicine, Alfred Health, Melbourne, Australia, 3Medical Oncology, Austin Health, Melbourne, Australia
1
Background: The impact of radiotherapy (RT) on the efficacy and toxicity of immune checkpoint inhibitors in patients (pts) with metastatic non-small cell-lung cancer (NSCLC) is unclear. Methods: We retrospectively identified pts with metastatic NSCLC treated with the anti-programmed death 1 (PD-1) antibodies nivolumab or pembrolizumab between January 2016 and May 2019 at two major oncology centres in Melbourne, Australia. Patient demographics, tumour characteristics, treatment history including radiotherapy (RT) use and toxicity were collected. Disease control rate (DCR), progression free survival (PFS) and overall survival (OS) were analysed and correlated with RT use. Results: 132 pts identified with interim analysis of 54 reported here. Median follow up was 19.4 months. Majority were male (61%) and 87% were smokers. 80% had non-squamous histology, of these 9% had an EGFR mutation. Brain metastases were present in 41%. The median number of cycles of anti-PD1 treatment received was 5 and only 7%
v622 | NSCLC, Metastatic
started anti-PD-1 as first-line therapy. 36% received RT treatment either during or within 3 months of starting anti-PD1 treatment. Of patients that received RT, 74% were treated with extra-thoracic RT. The use of RT before or during anti-PD1 treatment did not result in an increase in high grade immune-related adverse events. The DCR was 35%. The median PFS was 2 months (95% CI 0.5 – 29) and OS 9.7 months (95% CI 1.0 – 31). Pts who received RT had a numerically shorter PFS than those that did not (1.5 vs 2 months, p ¼ 0.668) but numerically longer OS (8.1 vs 7.2 months, p ¼ 0.857). Updated analysis with the full cohort and with longer follow-up will be presented. Conclusions: Radiotherapy did not significantly impact on survival in pts with metastatic NSCLC treated with anti-PD1 therapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1518P
Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real-world data from a European Cohort with focus on subgroups of interest
G. Mountzios1, D. Signorelli2, J. Rey Cobo3, M. Banini4, P. Economopoulou5, G. Lo Russo2, P.T. Baxevanos6, F. Roila4, A. de Toma2, G. Banna7, A. Christopoulou8, B. Jimenez9, H. Linardou10, A. Calles11, D. Galetta12, A. Addeo13, A. Camerini14, P.A. Kosmidis15, M.C. Garassino16, G. Metro17 1 2nd Department of Medical Oncology, Henry Dunant Hospital Center, Athens, Greece, 2 Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 3Oncology, Geneva University Hospital, Geneva, Switzerland, 4S.C. Oncologia, Ospedale Santa Maria della Misericordia, Perugia, Italy, 5Medical Oncology, Attikon University Hospital, Athens, Greece, 6Hematology Dept, Agios Savvas Regional Cancer Hospital, Athens, Greece, 7Medical Oncology, Ospedale Cannizzaro, Catania, Italy, 8 Medical Oncology, Agios Andreas General Hospital of Patras, Athens, Greece, 9Medical Oncology, Hospital HM Sanchinarro, Madrid, Spain, 10Oncology Dept, Metropolitan Hospital, Athens, Greece, 11Medical Oncology, Hospital General Universitario Gregorio Maranon, Madrid, Spain, 12Medical Thoracic Oncology Unit, IRCCS Istituto Oncologico “Giovanni Paolo II”, Bari, Italy, 13Medical Oncology, Hoˆpitaux Universitaires de Gene`ve HUG, Geneva, Switzerland, 14U.O.C. Oncologia, Ospedale "Versilia", Lido Di Camaiore, Italy, 152nd Department of Medical Oncology, Hygeia Hospital, Marousi, Greece, 16 Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy, 17 Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy Background: Real-world data regarding clinical outcomes associated with first-line pembrolizumab (pembro) monotherapy among specific subgroups of NSCLC patients are lacking. Methods: A comprehensive clinicopathological database of patients with NSCLC and PD-L1>50% treated with frontline pembro in 14 centers in Italy, Spain, Greece and Switzerland was retrospectively created. Post-progression outcomes have been previously reported. Clinical outcomes in specific subgroups of interest are presented in the current report. Analysis was performed using the SAS 9.3 software. Multivariate analysis was performed with the Cox regression model. Results: Among 173 eligible patients, median age at diagnosis was 68 years, 65% were male, 88% were current or former smokers, 25% had an ECOG PS > ¼2, histology was 67% adeno, 21% squamous, 20% had brain mets, 15% had liver mets at diagnosis and 28% received steroids at the beginning and/or during treatment. Thirty patients (17.4%) received pembro despite having non-metastatic disease (stage I-IIIC), as deemed medically inoperable or ineligible for definite chemo-radiotherapy. Hazard Ratios for OS, with corresponding 95% CIs and p-values for specific subgroups were as follows: Elderly patients ( >70 years): HR ¼ 0.85 (0.52-1.38), p ¼ 0.51; Brain mets: HR ¼ 1.17 (0.63-2.18), p ¼ 0.63; Stage I-IIIC: HR ¼ 0.56 (0.22-1.39), p ¼ 0.21; PS > ¼2: HR ¼ 1.73 (1.55-1.84), p < 0.0001; Steroid use: HR ¼ 3.27 (1.95-5.50), p < 0.0001; Platinum-based doublet 2nd line : HR ¼ 0.65 (0.29-1.47), p ¼ 0.30. In multivariate analysis, PS and the use of steroids remained independent predictors of survival. Conclusions: Real-world data in a large retrospective cohort of patients with NSCLC and PD-L1>50% indicate that 1) Pembro frontline is also active in inoperable stage IIIIC patients, 2) Elderly patients (>70 years) derive similar survival benefit to younger ones, except from those with PS > ¼2, 3) Steroid use at the beginning and/or during treatment is associated with a three-fold increase in the risk of death. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: G. Mountzios: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca Greece; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Greece; Honoraria (self), Travel / Accommodation / Expenses: Pfizer Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD Hellas; Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis Greece. G. Banna: Advisory / Consultancy: Janssen; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: AstraZeneca; Travel /
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.038/5577832 by guest on 26 October 2019
Fujimoto: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd. K. Hosoya: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.
Annals of Oncology