- Email: [email protected]
P1.01-058 Real World Data with Nivolumab: Experience in Argentina
November 2017
Abstracts
Conclusion: Nivolumab in NSCLC routine clinical practice is a safe and active alternative to chemotherapy. Nivolumab achieve a good outcome in both histologies, SqCC and Non-SqCC, but we detected a longer PFS in SqCC. Adverse events were as expected, grade 1 and 2. Keywords: anti PD-1, Nivolumab, Non-small-cell lung cancer
2
3
4
clinical efficacy. PS, the use of corticoids and immune-mediated toxicity seem to be conditions which could affect clinical outcomes. Keywords: Nivolumab Argentina
P1.01-059 Combination Pembrolizumab and Low Dose Weekly Carboplatin/Paclitaxel for Patients with Recurrent/ Metastatic NSCLC and PS of 2
P1.01-058 Real World Data with Nivolumab: Experience in Argentina 1
S1917
5
C. Martin, L. Lupinacci, F. Perazzo, C. Bas, O. Carranza, C. Puparelli,1 R. Kowalyzyn,6 I. Magri,7 M. Varela,8 E. Richardet,9 K. Vera,10 S. Foglia,11 I. Jerez,12 E. Aman,13 G. Martinengo,14 E. Batagel,15 A. Dri,16 N. Pilnik,17 M. Roa,18 P. Mando,1 F. Tsou,1 G. Recondo,19 F. Cayol,2 F. Marcos,5 S. Sena,4 C. Bagnes,20 J. Minatta,21 M. Rizzo1 1Department of Clinical Oncology, Instituto Alexander Fleming, Buenos Aires/AR, 2Oncologia, Hospital Italiano, Buenos Aires/AR, 3Oncologia, Cemic, Buenos Aires/AR, 4Oncologia, Hospital Aleman, Buenos Aires/AR, 5Oncologia, Hospital Privado de La Comunidad, Mar Del Plata/AR, 6Oncologia, Clinica Viedma, Viedma/AR, 7 Oncologia, Reina Fabiola, Còrdoba/AW, 8Oncologia, Coiba, Buenos Aires/AR, 9Oncologia, Instituto Oncológico Córdoba, Còrdoba/AR, 10 Oncologia, Hospital Britanico, Buenos Aires/AR, 11Oncologia, Hospital Oncològico Lanus, Lanus/AR, 12Oncologia, Sanatorio Allende, Còrdoba/ AR, 13Oncologia, Swiss Medical Group, Buenos Aires/AR, 14Oncologia, Sanatorio Parque, Rosario/AR, 15Hospital Militar Central, Buenos Aires/ AM, 16Oncologia, Instituto Oncològico de Rosario, Rosario/AR, 17 Oncologia, Tránsito Cáceres, Còrdoba/AR, 18Hospital Perrando, Resistencia/AR, 19Oncology. Internal Medicine, Cemic, Buenos Aires/AR, 20 Oncologia, Hospital Tornu, Buenos Aires/AR, 21Oncology, Hospital Italiano, Buenos Aires/AR Background: Nivolumab has improved overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients. Analysis of the use of these drugs in real world provides more evidence about efficacy and toxicity. We describe here the experience of the use of nivolumab in NSCLC in Argentina. Method: NSCLC patients (pts) who received nivolumab between 6/2015 12/2016. Patients consented their respective physicians to be treated on a drug expanded access program. Data was collected retrospectively by the physician. Images and follow up were done according to physician’s discretion. Adverse events were classified according to CTC3.1. Responses were evaluated according to RECIST 1.1 criteria. DFS and OS was assessed. All pts who received at least one dose of Nivolumab were evaluated for toxicity. Result: N 109. Fup 8.83 m (IQR 3.4-12.67). 57.8% men, 29.4% current smoker, 78.0% non-squamous, 8.3% EGFR mutated. Chemotherapy lines before nivolumab 2 md (r 1-4), and 59.6% received radiotherapy. 89% received previously platinum based chemotherapy. Sites of relapse or progression before nivolumab were: lung (75.2%), lymph nodes (47.7%), bone (19.3%), liver (11.9%), central nervous system (11.0%), and adrenal gland (13.8%). PS 0 26.6%, 1 56.0%, 2 13.8% and 3 1.8%. Cycles of nivolumab 10 Md (IQR 3-18). Drug related toxicity 78.9%. Grade 2-3 28.4%. Corticoid use 33.9%. Responses were evaluated in 104 pts who had as best response CR 2/104 (2%), PR 28/104 (27%), SD 33/104 (32%) and PD 41/104 (39%). Time to the best response was 4.0 m (IQR 2.3-5.9). DFS 6.1 m (IQR 2.4-13.1) and OS 12.3 m (IQR 4.1-NR). Univariate analysis revealed that absence of corticoids use (p¼0.034), toxicity grade 1-3 (p¼0.0025), PS1 (p¼0.049), age50 (p¼ 0.0011) were associated with longer DFS; PS1 (p<0.001) and toxicity grade 1-3 (p¼0.001) were associated with longer OS. In multivariate cox regression analysis, toxicity grade 1-3 (HR 0.44 CI95% 0.24-0.81, p¼0.008) and age50 (HR 0.28 CI95% 0.13-0.61, p¼0.001) were associated with longer DFS while corticoids use was associated with shorter DFS (HR 2.06 CI95% 1.22-3.48, p¼0.007); toxicity grade 1-3 (HR 0.28 CI95% 0.14-0.54, p<0.0001) and PS1 (HR 0.16 CI95% 0.08-0.31, p<0.0001) were associated with longer OS. Conclusion: The use of Nivolumab in a real world setting, in heavily pre-treated NSCLC patients was well tolerated and showed promising
T. Ahmed,1 P. Triozzi,1 S. Addo,2 M. Kooski,1 W. Petty,1 J. Ruiz,1 S. Grant,1 R. D’Agostino,1 M. Bonomi1 1Hematology and Oncology, Wake Forest Comprehensive Cancer Center, Winston Salem, NC/US, 2 Internal Medicine, Wake Forest School of Medicine, Winston Salem, NC/US Background: Chemotherapy and immunotherapy have been shown to be beneficial for patients with non-small cell lung cancer (NSCLC) and performance status (PS) of 0 or 1; there still is debate, however, regarding its efficacy for patients with a PS of 2 which comprises approximately 30% of the NSCLC population. Pre-clinical data have demonstrated that low dose carboplatin/paclitaxel have resulted in superior immune efficacy compared to the maximum tolerated dose regimen. Given the significant unmet need for treatment options in this patient population, our study evaluated low-dose weekly carboplatin/ paclitaxel combined with pembrolizumab in patients with NSCLC and a PS of 2. Method: Patients with metastatic or recurrent NSCLC and PS of 2 were randomized to single agent pembrolizumab at 200mg every 3 weeks or pembrolizumab plus weekly carboplatin AUC 1 and paclitaxel 25 mg/m2 irrespective to PDL-1 status. Response was determined using immune-related RECIST, and toxicity was graded using CTCAE 4.0. Result: Between 6/2016 and 2/2017, 20 patients were enrolled, and 19 patients were evaluable for response. The median age was 69 years (54-83). All 19 patients (100%) had a PS of 2. Ten patients were randomized to the single agent arm and 9 patients to the combination arm. Six patients received the therapy as second line (2 combination arm and 4 single agent arm). Mean 3 week cycles per patient: 9 (4-16) in combination arm and 7 (2-14) in single arm group. Response at 9 weeks in the combination arm: partial response (PR) 6 (67%), stable disease (SD) 2 (22%), and progressive disease (PD) 1 (11%). Response at 9 weeks in the single agent arm, PR 2 (20%), SD 4 (40%), and PD 4 (40%). Adverse events in combination arm: 1 (11%) discontinued therapy due to grade 3 fatigue, 3 (33%) discontinued carboplatin due to allergic reactions at 7, 9, and 10 months of treatment but continued pembrolizumab and paclitaxel, and 1 (11%) on hormone replacement therapy due to treatment-induced hypothyroidism. Adverse events in single agent arm: 1 (10%) discontinued treatment due to complete A-V block successfully resolved with pacemaker insertion, and 2 (20%) are on hormone replacement therapy due to treatment-induced hypothyroidism. Conclusion: Combination pembrolizumab and weekly low dose carboplatin/paclitaxel is an active and well tolerated regimen in patients with advanced NSCLC with PS of 2. Keywords: NSCLC, poor performance status, Immunotherapy
P1.01-060 Nivolumab after Progression to Platinum- Based Chemotherapy in Advanced Non-Small-Cell Lung Cancer (NSCLC) M. López Flores, P. Diz Taín, I. Delgado Sillero, L. Sánchez Cousido, A. López González, M. Pedraza Lorenzo, Á. Rodríguez Sánchez, C. Castañón López, B. Nieto Mangudo, F. García Casabal, L. De Sande González, A. García Palomo Medical Oncology, Complejo Asistencial Universitario de León, Leon/ES Background: In patients with advanced nonesmall-cell lung cancer (NSCLC), docetaxel has been established as the second line of treatment after
Abstracts
Conclusion: Nivolumab in NSCLC routine clinical practice is a safe and active alternative to chemotherapy. Nivolumab achieve a good outcome in both histologies, SqCC and Non-SqCC, but we detected a longer PFS in SqCC. Adverse events were as expected, grade 1 and 2. Keywords: anti PD-1, Nivolumab, Non-small-cell lung cancer
2
3
4
clinical efficacy. PS, the use of corticoids and immune-mediated toxicity seem to be conditions which could affect clinical outcomes. Keywords: Nivolumab Argentina
P1.01-059 Combination Pembrolizumab and Low Dose Weekly Carboplatin/Paclitaxel for Patients with Recurrent/ Metastatic NSCLC and PS of 2
P1.01-058 Real World Data with Nivolumab: Experience in Argentina 1
S1917
5
C. Martin, L. Lupinacci, F. Perazzo, C. Bas, O. Carranza, C. Puparelli,1 R. Kowalyzyn,6 I. Magri,7 M. Varela,8 E. Richardet,9 K. Vera,10 S. Foglia,11 I. Jerez,12 E. Aman,13 G. Martinengo,14 E. Batagel,15 A. Dri,16 N. Pilnik,17 M. Roa,18 P. Mando,1 F. Tsou,1 G. Recondo,19 F. Cayol,2 F. Marcos,5 S. Sena,4 C. Bagnes,20 J. Minatta,21 M. Rizzo1 1Department of Clinical Oncology, Instituto Alexander Fleming, Buenos Aires/AR, 2Oncologia, Hospital Italiano, Buenos Aires/AR, 3Oncologia, Cemic, Buenos Aires/AR, 4Oncologia, Hospital Aleman, Buenos Aires/AR, 5Oncologia, Hospital Privado de La Comunidad, Mar Del Plata/AR, 6Oncologia, Clinica Viedma, Viedma/AR, 7 Oncologia, Reina Fabiola, Còrdoba/AW, 8Oncologia, Coiba, Buenos Aires/AR, 9Oncologia, Instituto Oncológico Córdoba, Còrdoba/AR, 10 Oncologia, Hospital Britanico, Buenos Aires/AR, 11Oncologia, Hospital Oncològico Lanus, Lanus/AR, 12Oncologia, Sanatorio Allende, Còrdoba/ AR, 13Oncologia, Swiss Medical Group, Buenos Aires/AR, 14Oncologia, Sanatorio Parque, Rosario/AR, 15Hospital Militar Central, Buenos Aires/ AM, 16Oncologia, Instituto Oncològico de Rosario, Rosario/AR, 17 Oncologia, Tránsito Cáceres, Còrdoba/AR, 18Hospital Perrando, Resistencia/AR, 19Oncology. Internal Medicine, Cemic, Buenos Aires/AR, 20 Oncologia, Hospital Tornu, Buenos Aires/AR, 21Oncology, Hospital Italiano, Buenos Aires/AR Background: Nivolumab has improved overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients. Analysis of the use of these drugs in real world provides more evidence about efficacy and toxicity. We describe here the experience of the use of nivolumab in NSCLC in Argentina. Method: NSCLC patients (pts) who received nivolumab between 6/2015 12/2016. Patients consented their respective physicians to be treated on a drug expanded access program. Data was collected retrospectively by the physician. Images and follow up were done according to physician’s discretion. Adverse events were classified according to CTC3.1. Responses were evaluated according to RECIST 1.1 criteria. DFS and OS was assessed. All pts who received at least one dose of Nivolumab were evaluated for toxicity. Result: N 109. Fup 8.83 m (IQR 3.4-12.67). 57.8% men, 29.4% current smoker, 78.0% non-squamous, 8.3% EGFR mutated. Chemotherapy lines before nivolumab 2 md (r 1-4), and 59.6% received radiotherapy. 89% received previously platinum based chemotherapy. Sites of relapse or progression before nivolumab were: lung (75.2%), lymph nodes (47.7%), bone (19.3%), liver (11.9%), central nervous system (11.0%), and adrenal gland (13.8%). PS 0 26.6%, 1 56.0%, 2 13.8% and 3 1.8%. Cycles of nivolumab 10 Md (IQR 3-18). Drug related toxicity 78.9%. Grade 2-3 28.4%. Corticoid use 33.9%. Responses were evaluated in 104 pts who had as best response CR 2/104 (2%), PR 28/104 (27%), SD 33/104 (32%) and PD 41/104 (39%). Time to the best response was 4.0 m (IQR 2.3-5.9). DFS 6.1 m (IQR 2.4-13.1) and OS 12.3 m (IQR 4.1-NR). Univariate analysis revealed that absence of corticoids use (p¼0.034), toxicity grade 1-3 (p¼0.0025), PS1 (p¼0.049), age50 (p¼ 0.0011) were associated with longer DFS; PS1 (p<0.001) and toxicity grade 1-3 (p¼0.001) were associated with longer OS. In multivariate cox regression analysis, toxicity grade 1-3 (HR 0.44 CI95% 0.24-0.81, p¼0.008) and age50 (HR 0.28 CI95% 0.13-0.61, p¼0.001) were associated with longer DFS while corticoids use was associated with shorter DFS (HR 2.06 CI95% 1.22-3.48, p¼0.007); toxicity grade 1-3 (HR 0.28 CI95% 0.14-0.54, p<0.0001) and PS1 (HR 0.16 CI95% 0.08-0.31, p<0.0001) were associated with longer OS. Conclusion: The use of Nivolumab in a real world setting, in heavily pre-treated NSCLC patients was well tolerated and showed promising
T. Ahmed,1 P. Triozzi,1 S. Addo,2 M. Kooski,1 W. Petty,1 J. Ruiz,1 S. Grant,1 R. D’Agostino,1 M. Bonomi1 1Hematology and Oncology, Wake Forest Comprehensive Cancer Center, Winston Salem, NC/US, 2 Internal Medicine, Wake Forest School of Medicine, Winston Salem, NC/US Background: Chemotherapy and immunotherapy have been shown to be beneficial for patients with non-small cell lung cancer (NSCLC) and performance status (PS) of 0 or 1; there still is debate, however, regarding its efficacy for patients with a PS of 2 which comprises approximately 30% of the NSCLC population. Pre-clinical data have demonstrated that low dose carboplatin/paclitaxel have resulted in superior immune efficacy compared to the maximum tolerated dose regimen. Given the significant unmet need for treatment options in this patient population, our study evaluated low-dose weekly carboplatin/ paclitaxel combined with pembrolizumab in patients with NSCLC and a PS of 2. Method: Patients with metastatic or recurrent NSCLC and PS of 2 were randomized to single agent pembrolizumab at 200mg every 3 weeks or pembrolizumab plus weekly carboplatin AUC 1 and paclitaxel 25 mg/m2 irrespective to PDL-1 status. Response was determined using immune-related RECIST, and toxicity was graded using CTCAE 4.0. Result: Between 6/2016 and 2/2017, 20 patients were enrolled, and 19 patients were evaluable for response. The median age was 69 years (54-83). All 19 patients (100%) had a PS of 2. Ten patients were randomized to the single agent arm and 9 patients to the combination arm. Six patients received the therapy as second line (2 combination arm and 4 single agent arm). Mean 3 week cycles per patient: 9 (4-16) in combination arm and 7 (2-14) in single arm group. Response at 9 weeks in the combination arm: partial response (PR) 6 (67%), stable disease (SD) 2 (22%), and progressive disease (PD) 1 (11%). Response at 9 weeks in the single agent arm, PR 2 (20%), SD 4 (40%), and PD 4 (40%). Adverse events in combination arm: 1 (11%) discontinued therapy due to grade 3 fatigue, 3 (33%) discontinued carboplatin due to allergic reactions at 7, 9, and 10 months of treatment but continued pembrolizumab and paclitaxel, and 1 (11%) on hormone replacement therapy due to treatment-induced hypothyroidism. Adverse events in single agent arm: 1 (10%) discontinued treatment due to complete A-V block successfully resolved with pacemaker insertion, and 2 (20%) are on hormone replacement therapy due to treatment-induced hypothyroidism. Conclusion: Combination pembrolizumab and weekly low dose carboplatin/paclitaxel is an active and well tolerated regimen in patients with advanced NSCLC with PS of 2. Keywords: NSCLC, poor performance status, Immunotherapy
P1.01-060 Nivolumab after Progression to Platinum- Based Chemotherapy in Advanced Non-Small-Cell Lung Cancer (NSCLC) M. López Flores, P. Diz Taín, I. Delgado Sillero, L. Sánchez Cousido, A. López González, M. Pedraza Lorenzo, Á. Rodríguez Sánchez, C. Castañón López, B. Nieto Mangudo, F. García Casabal, L. De Sande González, A. García Palomo Medical Oncology, Complejo Asistencial Universitario de León, Leon/ES Background: In patients with advanced nonesmall-cell lung cancer (NSCLC), docetaxel has been established as the second line of treatment after