G V Scagliotti1, C Gridelli2, F de Marinis3, M Thomas4, M Dediu5, J-L Pujol6, C Manegold7, B San Antonio8, P M Peterson9, W John9, N Chouaki10, C Visseren-Grul11, L G Paz-Ares12. 1. University of Torino at S. Luigi Hospital, Orbassano, Torino, Italy. 2. S. Giuseppe Moscati Hospital, Avellino, Italy. 3. European Institute of Oncology, Thoracic Oncology Division, Milan, Italy. 4. Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Germany. 5. Institute of Oncology Bucharest, Bucharest, Romania. 6. Montpellier Academic Hospital, Montpellier, France. 7. Heidelberg University Medical Center, Mannheim, Germany. 8. Eli Lilly and Company, Madrid, Spain. 9. Eli Lilly and Company, Indianapolis, IN, USA. 10. Eli Lilly and Company, Suresnes, Hauts de Seine, France. 11. Eli Lilly and Company, Houten, The Netherlands. 12. Instituto de Biomedicina de Sevilla (University Hospital Virgen del Rocío, CSIC and Seville University), Seville, Spain. Electronic address: lpazares@hotmail.com.
Abstract
OBJECTIVES: Two phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500mg/m(2) plus cisplatin 75mg/m(2) every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression. METHODS:Overall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. RESULTS: Outcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p=0.117, HR=1.16; median OS: 14.0 versus 14.2 months, p=0.979, HR=1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p<0.00001, HR=0.66; median OS: 16.9 versus 14.2 months, p=0.003, HR=0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. CONCLUSIONS: The across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.
RCT Entities:
OBJECTIVES: Two phase III trials of advanced NSCLCpatients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500mg/m(2) plus cisplatin 75mg/m(2) every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression. METHODS: Overall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. RESULTS: Outcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p=0.117, HR=1.16; median OS: 14.0 versus 14.2 months, p=0.979, HR=1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p<0.00001, HR=0.66; median OS: 16.9 versus 14.2 months, p=0.003, HR=0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. CONCLUSIONS: The across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.
Authors: Naiyer A Rizvi; Matthew D Hellmann; Julie R Brahmer; Rosalyn A Juergens; Hossein Borghaei; Scott Gettinger; Laura Q Chow; David E Gerber; Scott A Laurie; Jonathan W Goldman; Frances A Shepherd; Allen C Chen; Yun Shen; Faith E Nathan; Christopher T Harbison; Scott Antonia Journal: J Clin Oncol Date: 2016-06-27 Impact factor: 44.544