Abstract 1057
Background
Current guidelines recommend chemotherapy with nab-P/G or FFX as the preferred first-line (1L) treatment for metastatic (m)PC pts with good performance status. However, no clinical trial has directly compared 1L nab-P/G vs FFX in mPC or aPC. We conducted a systematic review of the real-world comparative effectiveness of nab-P/G vs FFX in this setting.
Methods
Embase, Medline, and ASCO GI 2018 were searched through January 2018 for real world, retrospective studies directly comparing 1L nab-P/G vs FFX in mPC/aPC. Radiotherapy studies were excluded.
Results
550/580 records did not meet eligibility criteria, mainly as they were not comparative (264) nor 1L (188). After removing 5 duplicates, the remaining 25 studies (16 mPC; 9 aPC) assessed > 5464 pts who received nab-P/G or FFX. Generally, a lower proportion of pts in the nab-P/G group (range, 59% - 100%) had an ECOG PS score of 0 or 1 vs FFX (82% - 100%) (12 studies). Median overall survival (OS; 19 studies) ranged from 5.5 mo to “not reached” for nab-P/G, and 8.6 to 15.9 mo for FFX (Table); median progression-free survival (12 studies) ranged from 4 to 8.5 mo and 3.7 to 11.7 mo, respectively. In 2 studies that reported OS based on ECOG PS, the median OS for pts with ECOG PS 0/1 was 12.1 and 14.1 mo for nab-P/G vs 11.4 and 13.7 mo for FFX. Overall response rates ranged from 10% to 41% for nab-P/G and 6% to 34% for FFX (4 studies), and disease control rates ranged from 50% to 92% and 56% to 89%, respectively (5 studies). Safety outcomes were heterogeneously reported in 1667 pts (10 studies) receiving nab-P/G or FFX (Table).Table: 724P
| Study | n (1L) | Median 1L OS, mo | Median 1L PFS, mo | Grade ≥ 3 AEs | |||||
|---|---|---|---|---|---|---|---|---|---|
| nab-P/G | FFX | nab-P/G | FFX | nab-P/G | FFX | AE | nab-P/G | FFX | |
| Beyer 2016 (mPC) | 19 | 57 | 7 | 12 | NR | NR | NR | NR | |
| Park 2016 (mPC) | 18 | 9 | 6.1 | 9.9 | NR | NR | NR | NR | |
| Braiteh 2017 (mPC) | 122 | 80 | 8.6a | 8.6a | NR | NR | Neutropenia Febrile neutropenia Anemia Thrombocytopenia | 28% 1% 13% 11% | 30% 3% 6% 14% |
| Caponnetto 2017 (mPC) | 20 | 23 | NR | NR | 6 | 5 | NR | NR | |
| Cartwright 2017 (mPC) | 255 | 159 | 9.8b | 11.4b | NR | NR | NR | NR | |
| Cherniawsky 2017 (aPC)c | NR | NR | 10 | 11 | 6.9 | 8.8 | NR | NR | |
| Javed 2017 (mPC) | 80 | 191 | 7.0 | 9.0 | NR | NR | NR | NR | |
| Kasi 2017 (aPC)c | 47 (33) | 107 (56) | 10.8 | 15.9 | 5.7 | 11.7 | Neutropenia Peripheral neuropathy Diarrhea Anemia Thrombocytopenia Elevated transaminases Elevated creatinine | 17% 6% 0% 31% 6% 6% 4% | 33% 6% 5% 14% 28% 4% 3% |
| Maeda 2017 (aPC)c | 9 (NR) | 16 (NR) | 11.5 | 13.1 | 6.1 | 6.3 | NR | NR | |
| Mañes-Sevilla 2017 (mPC) | 20 | 15 | 9.2 | 11.4 | 5.4 | 7.1 | Any | 35% | 41% |
| Muranaka 2017 (aPC)c | 22 (17) | 16 (1) | Not reached | 9.9 | 6.5 | 3.7 | Neutropenia Peripheral neuropathy Febrile neutropenia Diarrhea Anemia Nausea Anorexia Thrombocytopenia Vomiting | 55% 0% 9% 0% 18% 0% 5% 14% 0% | 69% 0% 19% 0% 6% 6% 6% 6% 0% |
| Papneja 2017 (aPC)c | 33 (21) | 86 (70) | 9 | 9 | 4 | 6 | NR | NR | |
| Shahda 2017 (aPC)c | NR | NR | 11.4-14.4d | 11.3-12.3d | 4.6-6.1d | 5.3-9.4d | NR | NR | |
| Wang 2017 (aPC)c | 87 (66) | 92 (55) | 10.5 (10.0) | 14.1 (9.4) | 8.5 (8.3) | 8.4 (6.6) | NR | NR | |
| Watanabe 2017e (mPC) | 65 | 70 | 14.0 | 11.5 | 6.5 | 5.7 | Neutropenia Peripheral neuropathy Febrile neutropenia Diarrhea Anorexia | 45% 5% 2% 2% 3% | 47% 4% 9% 1% 13% |
| Barrera 2018 (mPC) | 31 | 44 | 8.1 | 9.9 | 4.6 | 5.8 | Neutropenia Peripheral neuropathy Fatigue | 13% 7% 26% | 20% 4% 11% |
| Franco 2018 (aPC)c | 49 (NR) | 87 (NR) | 13 | 13 | NR | NR | NR | NR | |
| Helen 2018 (aPC)c | NR | NR | NR (5.5 | NR (8.8) | NR | NR | NR | NR | |
| Hwang 2018 (mPC) | 149 | 159 | 11.4 | 9.6 | 6.8 | 5.0 | NR | NR | |
| Kim 2018 (mPC) | 337 | 317 | 12.1f | 13.8f | NR | NR | NR | NR | |
| Totalg | 1363 (1253) | 1528 (1306) |
Reported as database persistence, a proxy for OS.
bFor pts with ECOG PS 0/1, OS was 12.1 mo for nab-P/G and 11.4 mo for FFX.
caPC includes mPC. The numbers in parentheses are for pts with mPC.
dBiomarker study observing homologous recombination deficiency low vs high in each treatment regimen with data presented here as a range.
eModified FFX (no bolus 5-FU and reduced dose irinotecan).
fFor pts with ECOG PS 0/1, OS was 14.1 mo for nab-P/G and 13.7 mo for FFX.
gRepresents minimum as some studies did not report the number of pts. The numbers in parentheses are for pts with mPC. 1L, first line; AE, adverse event; aPC, advanced pancreatic cancer; FFX, FOLFIRINOX; mPC, metastatic pancreatic cancer; nab-P/G, nab-paclitaxel/gemcitabine; NR, not reported; OS, overall survival; PFS, progression-free survival.
Conclusions
Several real-world studies have compared the effectiveness of nab-P/G vs FFX, highlighting the clinical significance. A systematic review of these studies shows that nab-P/G and FFX have comparable effectiveness in mPC/aPC. Differences were observed in the toxicity profiles for the 2 regimens, which may drive treatment decisions. Table. Studies reporting OS, PFS, and safety.
Clinical trial identification
Legal entity responsible for the study
Celgene Corporation.
Funding
Celgene Corporation.
Editorial Acknowledgement
Editorial assistance was provided by Narender Dhingra, MediTech Media.
Disclosure
E.G. Chiorean: Advisor: Celgene, Genentech, Novocure, Pfizer; Research funding: Boehringer Ingelheim, Celgene, Ignyta, Incyte, Lilly, Stemlive. G. Giordano: Honoraria: Celgene, Sanofi; Consultancy: Celgene; Travel accomodation expenses, Celgene. G. Kim: Consultant, Speaker: Celgene, Ipsen. S-E. Al-Batran: Consultancy: Bristo-Myers Squibb, Celgene, Lilly, Merck, Roche, Servier; Speaker: Celgene, Lilly, Nordic Bioscience, Roche; research funding, Celgene, Hospira, Lilly, Medac, Novartis, Roche, Vibor. All other authors have declared no conflicts of interest.