- Email: [email protected]
Impact of corticosteroids and antibiotics on efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer
abstracts
Annals of Oncology Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi. E. Paillaud: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self): Servier; Honoraria (self), Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.
1290P
Association of programmed cell death 1 (PD-1) inhibitor therapy with overall survival (OS) in stage IV melanoma treated with targeted therapies
Background: The impact of oncology drug regulatory approvals on population-level patient (pt) outcomes is often unknown. Before targeted therapies, chemotherapy treatment of stage IV melanoma resulted in minimal OS improvement. To understand how PD-1 inhibitor approval influenced OS in treatment eligible stage IV melanoma pts, we assessed OS before and after the US Food and Drug Administration approval date of pembrolizumab (P), a second generation (2nd gen) immune checkpoint inhibitor (ICI), in a cohort treated with targeted therapies. Methods: US-based pts diagnosed with stage IV melanoma from 1/1/2011 to 3/31/2019 and receiving BRAF/MEK inhibitors or ICI in first-line (1L) in the deidentified nationwide Flatiron Health electronic health record-derived database were eligible. We used a multivariable Cox model indexed to 1L start and adjusted for age. Follow-up time relative to approval of P (9/4/2014) was a time-varying covariate. Results: Of 882 pts, 692 (78.5%) started 1L after P approval. Of those, 40.6% (n ¼ 281) received 2nd gen ICI and 27.3% (n ¼ 189) received combination ICI therapy in 1L. During pre-approval, 56.3% (n ¼ 107) received 1L first gen ICI (CTLA-4 inhibitor). Pre-approval pts were younger than post-approval pts (median 64.0 [IQR: 57.0, 72.8] vs 68.0 yrs [IQR: 58.8, 77.0]; p < 0.001) but similar in other clinical and demographic characteristics. In unadjusted analyses, median OS was twice as long for post-approval pts compared to pre-approval pts (14.0 mos [95% CI: 11.6, 17.5] vs 6.7 [95% CI: 5.5, 9.2]; log rank ¼ 0.001). In the multivariable time-varying model, mortality risk decreased by 22% (HR ¼ 0.78 [95% CI: 0.62, 0.98]; p ¼ 0.035) following P approval. When comparing treatments during post-approval, unadjusted median OS was 8 mos longer in pts receiving combination ICI relative to those treated with 2nd gen ICI monotherapy in 1L (20.6 mos [95% CI: 14.0, not reached] vs 12.7 mos [95% CI: 9.7, 17.5]; log rank ¼ 0.069). Conclusions: Introduction of 2nd gen ICI therapy was associated with longer OS in stage IV melanoma pts treated with targeted therapies. Future analyses could assess outcomes relative to regulatory approvals for specific subpopulations, such as those who would have been excluded from trials. Legal entity responsible for the study: Flatiron Health, Inc. Funding: Flatiron Health, Inc., independent subsidiary of the Roche group. Disclosure: A.Z. Torres: Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche. R. Mathur: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K. Maignan: Full / Parttime employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Full / Part-time employment: Roche; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018). M. Tucker: Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K.J. Ciofalo: Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K.R. Carson: Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018). All other authors have declared no conflicts of interest.
1291P
Clinical outcomes of immune checkpoint inhibitors in older and younger patients with advanced solid tumours in a real-life setting
P. Corbaux1, D. Maillet2, A. Boespflug3, M. Locatelli Sanchez4, M. Perier Muzet3, M. Duruisseaux5, L. Kiakouama Maleka6, S. Dalle3, C. Falandry7, J. Peron2 1 Faculte´ de Me´decine Lyon-Sud, Universite´ de Lyon, Oullins, France, 2Medical Oncology, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 3Dermatology, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 4Respiratory Medicine, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 5Respiratory Medicine, Hoˆpital Louis Pradel-Hospices Civils de Lyon, Bron, France, 6Respiratory Medicine, Hoˆpital de la Croix-Rousse, Lyon, France, 7 Geriatrics Unit, Centre Hospitalier Lyon Sud, Pierre Be´nite, France
1292P
Impact of corticosteroids and antibiotics on efficacy of immunecheckpoint inhibitors in advanced non-small cell lung cancer
J. Mosquera Martinez1, M. Riuvadets2, M-R. Garcıa- Campelo1, J. Serra Lopez2, G. Anguera Palacios2, P. Gallardo Melo1, I. Sullivan2, A. Barba Joaquin2, M. Majem Tarruella2, C. Reboredo Rendo1, P. Cordeiro Gonzalez1 1 Medical Oncology Service, CHUAC - Complexo Hospitalario Universitario A Coru~ na, Spain, 2Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Background: Immune-checkpoint inhibitors (ICIs) are a standard-of-care in advanced non-small cell lung cancer (NSCLC). Corticosteroids are often used in symptomatic patients, but their immunosuppressive effect may reduce the efficacy of ICIs. We report our experience in NSCLC and the potential impact of on-treatment use of corticosteroids and antibiotics. Methods: Medical records of 267 patients with advanced NSCLC receiving ICIs from March 2013 to August 2018 were reviewed. Corticosteroid usage at the time of initiation or during ICIs treatment and administration of antibiotics from 3 months before the initiation of ICIs to 3 months after treatment end were collected. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survival (OS). A multivariable analysis was performed to study the influence of clinical characteristics on treatment efficacy. Results: 146 patients (55%) received corticosteroids: 43% for the treatment of irAEs and 57% for the management of baseline conditions. Prednisone (40%) and dexamethasone (35%) were the most commonly used. Median dose of prednisone equivalent was 50mg daily, 92% received 10mg prednisone equivalent daily. Median duration of corticosteroids was 59 days. OS was longer in the group that did not receive corticosteroids or received <10mg prednisone equivalent daily: 14.7 vs 8.3 months. No differences in PFS were observed: 4.6 vs 4.2 months. Patients with corticosteroids for baseline condition presented shorter median OS than the rest of the population: 6.5 vs 16.5 months. Multivariable analysis identified corticosteroids usage as an independent variable related to poorer outcomes. 141 patients (52.8%) received antibiotics. Quinolone (37%) and penicillin (33%) were the most commonly used. No correlation between the usage of antibiotics and efficacy of ICIs was found, with median OS of 10.2 vs 12.5 months. Conclusions: The use of 10mg of prednisone equivalent daily was associated with poorer outcomes, especially when given for baseline condition. No correlation was found between antibiotics and survival. Corticosteroids usage may identify a population with higher volume and aggressive tumors. Prudent use of corticosteroids needs to be warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Background: Age-related immune dysfunction might impair the efficacy of immune checkpoint inhibitors (ICIs) in older patients. We aimed to evaluate, in a real-life setting, if age was associated with long-term clinical outcomes and tolerance of ICIs. Methods: All patients receiving an ICI monotherapy [CTLA-4 or PD(L)-1 inhibitors] for the standard treatment of a locally advanced or metastatic cancer were included in
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz253 | v525
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz253.117/5577920 by guest on 26 October 2019
A.Z. Torres1, R. Mathur1, K. Maignan1, M. Tucker1, K.J. Ciofalo1, S. Khozin2, K.R. Carson1 Real-World Evidence, Flatiron Health Inc., New York, NY, USA, 2Oncology Center of Excellence, FDA, New York, NY, USA
1
this retrospective multicentric series (three hospitals in the Hospices Civils de Lyon, France). The primary endpoint was overall survival (OS). Progression-free survival (PFS) and immune-related adverse events (irAEs) were secondary endpoints. The impact of age was assessed using the threshold of 70 years. Results: Between January 2007 and October 2017, 410 patients were included in this series, for a total of 435 lines of treatment. One hundred and fifty lines (34%) were received by patients of 70 years or older. They were administered for a lung cancer (n ¼ 304, 74%), a melanoma (n ¼ 79, 19%) or a urologic cancer (n ¼ 27, 7%). Most of the administered treatments were PD(L)-1 inhibitors (n ¼ 356, 82%). Mean follow-up duration starting at treatment initiation was 46 months in the CTLA-4 cohort, and 20 months in the PD(L)-1 cohort. For both CTLA-4 inhibitors and PD(L)-1 inhibitors, there was no statistical association between age and OS (respectively, HR 0.8, 95% CI: 0.5-1.4; log-rank P ¼ 0.49 and HR ¼ 0.9, 95% CI: 0.7-1.1; Log-rank P ¼ 0.27) or PFS (respectively, HR ¼ 0.7, 95% CI: 0.4-1.1; log-rank P ¼ 0.13 or HR ¼ 0.9, 95% CI: 0.71.1; Log-rank P ¼ 0.19) in univariate analysis, and after adjusting on prognosis covariates. Older patients did not have more grade 3-4 irAEs (11% versus 12%, P ¼ 0.87). Conclusions: In this large real-world series, the long-term clinical outcomes were not statistically different between patients older or younger than 70 years who had received ICIs as a single agent in standard practice for an advanced solid tumor. Older patients did not have more severe immune-related adverse events. These data suggest that the use of ICI monotherapy for older patients may be safe with no specific monitoring. Legal entity responsible for the study: Julien Pe´ron. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi. E. Paillaud: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self): Servier; Honoraria (self), Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.
1290P
Association of programmed cell death 1 (PD-1) inhibitor therapy with overall survival (OS) in stage IV melanoma treated with targeted therapies
Background: The impact of oncology drug regulatory approvals on population-level patient (pt) outcomes is often unknown. Before targeted therapies, chemotherapy treatment of stage IV melanoma resulted in minimal OS improvement. To understand how PD-1 inhibitor approval influenced OS in treatment eligible stage IV melanoma pts, we assessed OS before and after the US Food and Drug Administration approval date of pembrolizumab (P), a second generation (2nd gen) immune checkpoint inhibitor (ICI), in a cohort treated with targeted therapies. Methods: US-based pts diagnosed with stage IV melanoma from 1/1/2011 to 3/31/2019 and receiving BRAF/MEK inhibitors or ICI in first-line (1L) in the deidentified nationwide Flatiron Health electronic health record-derived database were eligible. We used a multivariable Cox model indexed to 1L start and adjusted for age. Follow-up time relative to approval of P (9/4/2014) was a time-varying covariate. Results: Of 882 pts, 692 (78.5%) started 1L after P approval. Of those, 40.6% (n ¼ 281) received 2nd gen ICI and 27.3% (n ¼ 189) received combination ICI therapy in 1L. During pre-approval, 56.3% (n ¼ 107) received 1L first gen ICI (CTLA-4 inhibitor). Pre-approval pts were younger than post-approval pts (median 64.0 [IQR: 57.0, 72.8] vs 68.0 yrs [IQR: 58.8, 77.0]; p < 0.001) but similar in other clinical and demographic characteristics. In unadjusted analyses, median OS was twice as long for post-approval pts compared to pre-approval pts (14.0 mos [95% CI: 11.6, 17.5] vs 6.7 [95% CI: 5.5, 9.2]; log rank ¼ 0.001). In the multivariable time-varying model, mortality risk decreased by 22% (HR ¼ 0.78 [95% CI: 0.62, 0.98]; p ¼ 0.035) following P approval. When comparing treatments during post-approval, unadjusted median OS was 8 mos longer in pts receiving combination ICI relative to those treated with 2nd gen ICI monotherapy in 1L (20.6 mos [95% CI: 14.0, not reached] vs 12.7 mos [95% CI: 9.7, 17.5]; log rank ¼ 0.069). Conclusions: Introduction of 2nd gen ICI therapy was associated with longer OS in stage IV melanoma pts treated with targeted therapies. Future analyses could assess outcomes relative to regulatory approvals for specific subpopulations, such as those who would have been excluded from trials. Legal entity responsible for the study: Flatiron Health, Inc. Funding: Flatiron Health, Inc., independent subsidiary of the Roche group. Disclosure: A.Z. Torres: Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche. R. Mathur: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K. Maignan: Full / Parttime employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Full / Part-time employment: Roche; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018). M. Tucker: Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K.J. Ciofalo: Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K.R. Carson: Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018). All other authors have declared no conflicts of interest.
1291P
Clinical outcomes of immune checkpoint inhibitors in older and younger patients with advanced solid tumours in a real-life setting
P. Corbaux1, D. Maillet2, A. Boespflug3, M. Locatelli Sanchez4, M. Perier Muzet3, M. Duruisseaux5, L. Kiakouama Maleka6, S. Dalle3, C. Falandry7, J. Peron2 1 Faculte´ de Me´decine Lyon-Sud, Universite´ de Lyon, Oullins, France, 2Medical Oncology, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 3Dermatology, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 4Respiratory Medicine, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 5Respiratory Medicine, Hoˆpital Louis Pradel-Hospices Civils de Lyon, Bron, France, 6Respiratory Medicine, Hoˆpital de la Croix-Rousse, Lyon, France, 7 Geriatrics Unit, Centre Hospitalier Lyon Sud, Pierre Be´nite, France
1292P
Impact of corticosteroids and antibiotics on efficacy of immunecheckpoint inhibitors in advanced non-small cell lung cancer
J. Mosquera Martinez1, M. Riuvadets2, M-R. Garcıa- Campelo1, J. Serra Lopez2, G. Anguera Palacios2, P. Gallardo Melo1, I. Sullivan2, A. Barba Joaquin2, M. Majem Tarruella2, C. Reboredo Rendo1, P. Cordeiro Gonzalez1 1 Medical Oncology Service, CHUAC - Complexo Hospitalario Universitario A Coru~ na, Spain, 2Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Background: Immune-checkpoint inhibitors (ICIs) are a standard-of-care in advanced non-small cell lung cancer (NSCLC). Corticosteroids are often used in symptomatic patients, but their immunosuppressive effect may reduce the efficacy of ICIs. We report our experience in NSCLC and the potential impact of on-treatment use of corticosteroids and antibiotics. Methods: Medical records of 267 patients with advanced NSCLC receiving ICIs from March 2013 to August 2018 were reviewed. Corticosteroid usage at the time of initiation or during ICIs treatment and administration of antibiotics from 3 months before the initiation of ICIs to 3 months after treatment end were collected. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survival (OS). A multivariable analysis was performed to study the influence of clinical characteristics on treatment efficacy. Results: 146 patients (55%) received corticosteroids: 43% for the treatment of irAEs and 57% for the management of baseline conditions. Prednisone (40%) and dexamethasone (35%) were the most commonly used. Median dose of prednisone equivalent was 50mg daily, 92% received 10mg prednisone equivalent daily. Median duration of corticosteroids was 59 days. OS was longer in the group that did not receive corticosteroids or received <10mg prednisone equivalent daily: 14.7 vs 8.3 months. No differences in PFS were observed: 4.6 vs 4.2 months. Patients with corticosteroids for baseline condition presented shorter median OS than the rest of the population: 6.5 vs 16.5 months. Multivariable analysis identified corticosteroids usage as an independent variable related to poorer outcomes. 141 patients (52.8%) received antibiotics. Quinolone (37%) and penicillin (33%) were the most commonly used. No correlation between the usage of antibiotics and efficacy of ICIs was found, with median OS of 10.2 vs 12.5 months. Conclusions: The use of 10mg of prednisone equivalent daily was associated with poorer outcomes, especially when given for baseline condition. No correlation was found between antibiotics and survival. Corticosteroids usage may identify a population with higher volume and aggressive tumors. Prudent use of corticosteroids needs to be warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Background: Age-related immune dysfunction might impair the efficacy of immune checkpoint inhibitors (ICIs) in older patients. We aimed to evaluate, in a real-life setting, if age was associated with long-term clinical outcomes and tolerance of ICIs. Methods: All patients receiving an ICI monotherapy [CTLA-4 or PD(L)-1 inhibitors] for the standard treatment of a locally advanced or metastatic cancer were included in
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz253 | v525
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz253.117/5577920 by guest on 26 October 2019
A.Z. Torres1, R. Mathur1, K. Maignan1, M. Tucker1, K.J. Ciofalo1, S. Khozin2, K.R. Carson1 Real-World Evidence, Flatiron Health Inc., New York, NY, USA, 2Oncology Center of Excellence, FDA, New York, NY, USA
1
this retrospective multicentric series (three hospitals in the Hospices Civils de Lyon, France). The primary endpoint was overall survival (OS). Progression-free survival (PFS) and immune-related adverse events (irAEs) were secondary endpoints. The impact of age was assessed using the threshold of 70 years. Results: Between January 2007 and October 2017, 410 patients were included in this series, for a total of 435 lines of treatment. One hundred and fifty lines (34%) were received by patients of 70 years or older. They were administered for a lung cancer (n ¼ 304, 74%), a melanoma (n ¼ 79, 19%) or a urologic cancer (n ¼ 27, 7%). Most of the administered treatments were PD(L)-1 inhibitors (n ¼ 356, 82%). Mean follow-up duration starting at treatment initiation was 46 months in the CTLA-4 cohort, and 20 months in the PD(L)-1 cohort. For both CTLA-4 inhibitors and PD(L)-1 inhibitors, there was no statistical association between age and OS (respectively, HR 0.8, 95% CI: 0.5-1.4; log-rank P ¼ 0.49 and HR ¼ 0.9, 95% CI: 0.7-1.1; Log-rank P ¼ 0.27) or PFS (respectively, HR ¼ 0.7, 95% CI: 0.4-1.1; log-rank P ¼ 0.13 or HR ¼ 0.9, 95% CI: 0.71.1; Log-rank P ¼ 0.19) in univariate analysis, and after adjusting on prognosis covariates. Older patients did not have more grade 3-4 irAEs (11% versus 12%, P ¼ 0.87). Conclusions: In this large real-world series, the long-term clinical outcomes were not statistically different between patients older or younger than 70 years who had received ICIs as a single agent in standard practice for an advanced solid tumor. Older patients did not have more severe immune-related adverse events. These data suggest that the use of ICI monotherapy for older patients may be safe with no specific monitoring. Legal entity responsible for the study: Julien Pe´ron. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.