Survival Benefits of Chemotherapy for Patients with Advanced Pancreatic Cancer in A Clinical Real-World Cohort
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Overall Survival According to First-Line Treatment
2.3. Time to Treatment-Failure, Evaluation at the End of Treatment, and Protocol Adherence
2.4. Second-Line treatment
2.5. Adverse Events
3. Discussion
4. Materials and Methods
4.1. Patient Population
4.2. Patient and Tumor Characteristics
4.3. Chemotherapy Protocols
4.4. Outcome Measures
4.5. Dose Modifications and Protocol Adherence
4.6. Adverse Events
4.7. Statistical Analysis
4.8. Ethics Approval and Consent to Participate
4.9. Availability of Data and Material
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | Gemcitabine (n = 185) | Gemcitabine/ Capecitabine (n = 60) | Gemcitabine/Nab-Paclitaxel (n = 66) | 5-FU/Oxaliplatin/Irinotecan (n = 31) | 5-FU/Oxaliplatin (n = 35) | Other (n = 12) | Best Supportive Care (n = 206) | All Patients (n = 595) | p-Value¶ |
---|---|---|---|---|---|---|---|---|---|
Sex, no. (%) | |||||||||
Female | 94 (50.8) | 25 (41.7) | 33 (50) | 12 (38.7) | 14 (40) | 6 (50) | 94 (45.6) | 278 (46.7) | 0.713 |
Male | 91 (49.2) | 35 (58.3) | 33 (50) | 19 (61.3) | 21 (60) | 6 (50) | 112 (54.4) | 317 (53.3) | |
Age at diagnosis, years | |||||||||
Mean (range) | 70.6 (39.7–83.8) | 66.3 (38–81.7) | 64.9 (40.5–79.5) | 59.4 (39.7–71.9) | 65.7 (46.6–76.4) | 65.5 (44.2–76.1) | 73.1 (51–95.2) | 69.4 (38–95.2) | 0.000 |
Body mass index, no. (%) * | |||||||||
≤18.4 | 17 (9.2) | 6 (10) | 3 (4.5) | – | 1 (2.9) | – | 26 (12.6) | 53 (8.9) | 0.194 |
18.5–29.9 | 157 (84.9) | 52 (86.7) | 60 (90.9) | 30 (96.8) | 32 (91.4) | 12 (100) | 155 (75.2) | 498 (83.7) | |
≥30.0 | 10 (5.4) | 2 (3.3) | 3 (4.5) | 1 (3.2) | 2 (5.7) | – | 15 (7.3) | 33 (5.5) | |
ECOG PS, no. (%) * | |||||||||
0 | 40 (21.6) | 26 (43.3) | 21 (31.8) | 17 (54.8) | 12 (34.3) | 3 (25) | 22 (10.7) | 141 (23.7) | 0.000 |
1 | 88 (47.6) | 23 (38.3) | 39 (59.1) | 12 (38.7) | 17 (48.6) | 5 (41.7) | 49 (23.8) | 233 (39.2) | |
2 | 48 (25.9) | 7 (11.7) | 4 (6.1) | – | 3 (8.6) | 3 (25) | 44 (21.4) | 109 (18.3) | |
≥3 | 8 (4.3) | 1 (1.7) | – | 2 (6.5) | 2 (5.7) | 1 (8.3) | 44 (21.4) | 58 (9.7) | |
Diabetes, no. (%) * † | |||||||||
yes | 61 (33) | 4 (6.7) | 17 (25.8) | 7 (22.6) | 9 (25.7) | 2 (16.7) | 70 (34) | 170 (28.6) | 0.002 |
no | 123 (66.5) | 56 (93.3) | 48 (72.7) | 24 (77.4) | 26 (74.3) | 10 (83.3) | 133 (64.6) | 420 (70.6) | |
Alcohol abuse, no. (%) * † | |||||||||
yes | 10 (5.4) | 2 (3.3) | 1 (1.5) | – | 2 (5.7) | – | 18 (8.7) | 33 (5.5) | 0.414 |
no | 159 (85.9) | 53 (88.3) | 54 (81.8) | 26 (83.9) | 33 (94.3) | 9 (75) | 150 (72.8) | 484 (81.3) | |
former | 6 (3.2) | 3 (5) | 2 (3) | 1 (3.2) | – | – | 6 (2.9) | 18 (3) | |
Smoking, no. (%) * † | |||||||||
yes | 48 (25.9) | 12 (20) | 9 (13.6) | 1 (3.2) | 3 (8.6) | – | 34 (16.5) | 107 (18) | 0.003 |
no | 67 (36.2) | 24 (40) | 23 (34.8) | 19 (61.3) | 17 (48.6) | 4 (33.3) | 104 (50.5) | 258 (43.4) | |
former | 61 (33) | 21 (35) | 27 (40.9) | 10 (32.3) | 15 (42.9) | 5 (41.7) | 52 (25.2) | 191 (32.1) | |
Primary tumor location, no. (%) * | |||||||||
Head | 114 (61.6) | 36 (60) | 29 (43.9) | 15 (48.4) | 22 (62.9) | 5 (41.7) | 100 (48.5) | 321 (53.9) | 0.046 |
Body | 28 (15.1) | 8 (13.3) | 14 (21.2) | 9 (29) | 7 (20) | 2 (16.7) | 22 (10.7) | 90 (15.1) | |
Tail | 21 (11.4) | 4 (6.7) | 7 (10.6) | 2 (6.5) | 3 (8.6) | 2 (16.7) | 33 (16) | 72 (12.1) | |
Overlapping | 18 (9.7) | 8 (13.3) | 12 (18.2) | 3 (9.7) | – | 2 (16.7) | 33 (16) | 76 (12.8) | |
Ampulla of Vater | 2 (1.1) | 3 (5) | 3 (4.5) | 2 (6.5) | 3 (8.6) | 1 (8.3) | 10 (4.9) | 24 (4) | |
Metastasization, no. (%) ‡ | |||||||||
Non-local lymph nodes | 12 (6.5) | 3 (5) | 8 (12.1) | 1 (3.2) | 1 (2.9) | 2 (16.7) | 15 (7.3) | 42 (7.1) | 0.380 |
Liver | 93 (50.3) | 27 (45) | 37 (56.1) | 14 (45.2) | 10 (28.6) | 6 (50) | 119 (57.8) | 306 (51.4) | 0.047 |
Lung | 31 (16.8) | 7 (11.7) | 11 (16.7) | 1 (3.2) | 9 (25.7) | 2 (16.7) | 29 (14.1) | 90 (15.1) | 0.258 |
Peritoneum | 20 (10.8) | 6 (10) | 18 (27.3) | 4 (12.9) | 7 (20) | 4 (33.3) | 41 (19.9) | 100 (16.8) | 0.012 |
Other | 11 (5.9) | – | 3 (4.5) | – | 5 (14.3) | 2 (16.7) | 14 (6.8) | 35 (5.9) | 0.040 |
No. of metastatic sites, no. (%) ‡ | |||||||||
1 | 76 (41.1) | 30 (50) | 44 (66.7) | 11 (35.5) | 12 (34.3) | 5 (41.7) | 88 (42.7) | 266 (44.7) | 0.002 |
2 | 23 (12.4) | 5 (8.3) | 8 (12.1) | 2 (6.5) | 4 (11.4) | 2 (16.7) | 34 (16.5) | 78 (13.1) | |
≥3 | 7 (4.3) | – | 2 (4.5) | 1 (3.2) | – | 1 (8.3) | 8 (4.4) | 19 (3.7) | |
Morphology, no. (%) * | |||||||||
Adenocarcinoma | 166 (89.7) | 50 (83.3) | 56 (84.8) | 23 (74.2) | 33 (94.3) | 11 (91.7) | 152 (73.8) | 491 (82.5) | 0.169 |
Other | – | 1 (1.7) | 1 (1.5) | 1 (3.2) | 2 (5.7) | 1 (8.3) | 5 (2.4) | 11 (1.8) | |
CA 19–9, kE/l * § | |||||||||
Median (IQR) | 764 (124–5828) | 817.5 (76.5–3855.3) | 1390 (267–7620) | 626 (66–2330) | 142 (34.5–881) | 170 (79.3–2927.5) | 1309.5 (139.3–8975) | 908 (106–5814.5) | 0.002 |
Surgery | |||||||||
Tumor resection, no. (%) | 31 (16.8) | 5 (8.3) | 8 (12.1) | 2 (6.5) | 30 (85.7) | 7 (58.3) | 62 (30.1) | 145 (24.4) | 0.000 |
Median time to relapse, mo. (IQR) | 7.8 (3.9–14.5) | 15.7 (3.2–17.3) | 4 (2.2–12.9) | 14.2 (11.7–16.6) | 12.2 (9.8–15.9) | 11.5 (9.7–15.6) | 8.4 (5.8–12.8) | 9.4 (5.8–14.2) | 0.069 |
Adjuvant treatment, no. (%) ‖ | |||||||||
Total | 13 (7) | 4 (6.7) | 5 (7.6) | 2 (6.5) | 30 (85.7) | 7 (58.3) | 32 (15.5) | 93 (15.6) | 0.000 |
Completed | 7 (3.8) | 3 (5) | 3 (4.5) | 2 (6.5) | 24 (68.6) | 3 (25) | 12 (5.8) | 54 (9.1) | |
Interrupted | 6 (3.2) | 1 (1.7) | 2 (3) | – | 6 (17.1) | 4 (33.3) | 20 (9.7) | 39 (6.6) | |
Interventions, no. (%) | |||||||||
ERCP/PTC | 84 (45.4) | 23 (38.3) | 28 (42.4) | 20 (64.5) | 18 (51.4) | 6 (50) | 88 (42.7) | 267 (44.9) | 0.266 |
Exploration | 18 (9.7) | 6 (10) | 9 (13.6) | 7 (22.6) | 1 (2.9) | – | 6 (2.9) | 47 (7.9) | 0.000 |
Outcome | Gemcitabine (n = 185) | Gemcitabine/ Capecitabine (n = 60) | Gemcitabine/ Nab-Paclitaxel (n = 66) | 5-FU/Oxaliplatin/ Irinotecan (n = 31) | 5-FU/Oxaliplatin (n = 35) | Other (n = 12) | Best Supportive Care (n = 206) | p-Value |
---|---|---|---|---|---|---|---|---|
OS | ||||||||
Median OS, mo. (95% CI) | 6.6 (5.5–7.7) | 10.6 (7.8–13.3) | 9.8 (7.9–11.8) | 9.9 (8.1–11.7) | 5.8 (4.5–7) | 7.9 (2.2–13.7) | 1.8 (1.5–2.1) | 0.0001 |
Univariate HR, (95% CI) | 1 (ref) | 0.67 (0.49–0.91) | 0.72 (0.53–0.99) | 0.7 (0.46–1.06) | 0.95 (0.65–1.41) | – | 2.69 (2.18–3.32) | |
HR adjusted for co-variables *, (95% CI) | 1 (ref) | 0.57 (0.41–0.8) | 0.54 (0.38–0.76) | 0.5 (0.31–0.81) | 1.33 (0.84–2.1) | – | 2.4 (1.85–3.12) | |
Median OS in RCT of first-line treatment, mo. (95% CI) | ||||||||
Burris et al. [3] | 5.7 (–) | – | – | – | – | – | – | |
Cunningham et al. [6] | 6.2 (5.5–7.2) | 7.1 (6.2–7.8) | – | – | – | – | – | |
Conroy et al. [10] | 6.8 (5.5–7.8) | – | – | 11.1 (9–13.1) | – | – | – | |
Von Hoff et al. [9] | 6.7 (6–7.2) | – | 8.5 (7.9–9.5) | – | – | – | – | |
HR for death compared to gemcitabine in RCT, (95% CI) | ||||||||
Cunningham et al. [6] | 1 (ref) | 0.86 (0.72–1.02) | – | – | – | – | – | |
Conroy et al. [10] | 1 (ref) | – | – | 0.57 (0.45–0.73) | – | – | – | |
Von Hoff et al. [9] | 1 (ref) | – | 0.72 (0.62–0.83) | – | – | – | – | |
Time to treatment-failure | ||||||||
TTF, mo. (95% CI) | 3.3 (2.8–3.8) | 3.7 (2.4–4.9) | 5.1 (4.1–6) | 2.9 (2–3.8) | 2.8 (2.4–3.1) | 3.5 (2.1–4.8) | – | 0.08 |
Univariate HR, (95% CI) | 1 (ref) | 0.88 (0.66–1.18) | 0.78 (0.59–1.05) | 1.09 (0.74–1.62) | 1.43 (0.99–2.07) | – | – | |
HR adjusted for co-variables *, (95% CI) | 1 (ref) | 0.86 (0.62–1.2) | 0.62 (0.44–0.87) | 0.95 (0.57–1.57) | 1.8 (1.09–2.98) | – | – | |
Progression-free survival in RCT of first-line treatment, months (95% CI) | ||||||||
Burris et al. [3] | 3.7 (–) | – | – | – | – | – | – | |
Cunningham et al. [6] | 3.8 (2.9–4.8) | 5.3 (4.5–5.7) | – | – | – | – | – | |
Conroy et al. [10] | 3.3 (2.2–3.6) | – | – | 6.4 (5.5–7.2) | – | – | – | |
Von Hoff et al. [9] | 3.7 (3.6– 4) | – | 5.5 (4.5–5.9) | – | – | – | – | |
HR for disease progression compared to gemcitabine in RCT, (95% CI) | ||||||||
Cunningham et al. [6] | 1 (ref) | 0.78 (0.66–0.93) | – | – | – | – | – | |
Conroy et al. [10] | 1 (ref) | – | – | 0.47 (0.37–0.59) | – | – | – | |
Von Hoff et al. [9] | 1 (ref) | – | 0.69 (0.58–0.82) | – | – | – | – | |
Clinical evaluation at end of treatment | ||||||||
Progression, no. (%) | 68 (36.8) | 32 (53.3) | 35 (53) | 15 (48.4) | 16 (45.7) | – | – | 0.002 |
Stable disease, no. (%) | 23 (12.4) | 4 (6.7) | 5 (7.6) | 3 (9.7) | 2 (5.7) | – | – | |
Partial response, no. (%) | 7 (3.8) | 5 (8.3) | 8 (12.1) | 2 (6.5) | 3 (8.6) | – | – | |
Mixed response, no. (%) | 1 (0.5) | 1 (1.7) | 3 (4.5) | 2 (6.5) | 5 (14.3) | – | – | |
Death, no. (%) | 54 (29.2) | 5 (8.3) | 10 (15.2) | 0 (0) | 7 (20) | – | – | |
Not evaluated, no. (%) | 32 (17.3) | 13 (21.7) | 5 (7.6) | 9 (29) | 5 (14.3) | – | – |
Adverse event (CTCAE 4.02) | Gemcitabine (n = 185) | Gemcitabine/ Capecitabine (n = 60) | Gemcitabine/ Nab-Paclitaxel (n = 66) | 5-FU/ Oxaliplatin/ Irinotecan (n = 31) | 5-FU/ Oxaliplatin (n = 35) | Other (n = 12) | All Treated Patients (n = 389) | p-Value |
---|---|---|---|---|---|---|---|---|
Hematological adverse events, no. (%) | ||||||||
Anemia | ||||||||
All grades | 15 (8.1) | 3 (5) | 17 (25.8) | 5 (16.1) | 2 (5.7) | – | 42 (10.8) | 0.000 |
Grade ≥3 | (0) | (0) | 3 (4.5) | 2 (6.5) | 1 (2.9) | – | (0) | |
Platelet count decrease | ||||||||
All grades | 20 (10.8) | 3 (5) | 14 (21.2) | 2 (6.5) | 1 (2.9) | – | 38 (9.8) | 0.000 |
Grade ≥3 | 10 (5.4) | 1 (0.5) | 2 (1.1) | (0) | (0) | – | 13 (7) | |
White blood cell decrease | ||||||||
All grades | 11 (5.9) | 3 (5) | 14 (21.2) | 2 (6.5) | – | – | 38 (9.8) | 0.004 |
Grade ≥3 | 2 (1.1) | 2 (1.1) | 2 (1.1) | – | – | – | 6 (3.2) | |
Non-hematological adverse events, no. (%) | ||||||||
Bile duct obstruction | ||||||||
All grades | 6 (3.2) | 4 (6.7) | 3 (4.5) | 1 (3.2) | – | – | 14 (3.6) | 0.042 |
Grade ≥3 | 6 (3.2) | 4 (6.7) | 3 (4.5) | 1 (3.2) | – | – | 14 (3.6) | |
Diarrhea | ||||||||
All grades | 6 (3.2) | 3 (5) | 4 (6.1) | 5 (16.1) | 3 (8.6) | 1 (8.3) | 22 (5.7) | 0.000 |
Grade ≥3 | 2 (1.1) | 1 (1.7) | – | 2 (6.5) | 2 (5.7) | 1 (8.3) | 8 (2.1) | |
Fatigue | ||||||||
All grades | 19 (10.3) | 2 (3.3) | 2 (3) | 2 (6.5) | 2 (5.7) | 2 (16.7) | 29 (7.5) | 0.000 |
Grade ≥3 | 5 (2.7) | – | – | – | – | – | 5 (1.3) | |
Fever | ||||||||
All grades | 8 (4.3) | 2 (3.3) | 5 (7.6) | 1 (3.2) | 1 (2.9) | – | 17 (4.4) | 0.04 |
Grade ≥3 | 3 (1.6) | – | 2 (3) | – | – | – | 5 (1.3) | |
Nausea | ||||||||
All grades | 8 (4.3) | 3 (5) | 4 (6.1) | 1 (3.2) | 1 (2.9) | – | 17 (4.4) | 0.08 |
Grade ≥3 | 4 (2.2) | 2 (3.3) | – | – | – | – | 6 (1.5) | |
Peripheral sensory neuropathy | ||||||||
All grades | – | – | 14 (21.2) | 2 (6.5) | 1 (2.9) | – | 38 (9.8) | 0.000 |
Grade ≥3 | – | – | 3 (1.6) | – | – | – | 3 (1.6) | |
Sepsis | ||||||||
All grades (always Grade ≥4) | 15 (8.1) | – | 6 (9.1) | 2 (6.5) | 4 (11.4) | – | 27 (6.9) | 0.000 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Kordes, M.; Yu, J.; Malgerud, O.; Gustafsson Liljefors, M.; Löhr, J.-M. Survival Benefits of Chemotherapy for Patients with Advanced Pancreatic Cancer in A Clinical Real-World Cohort. Cancers 2019, 11, 1326. https://doi.org/10.3390/cancers11091326
Kordes M, Yu J, Malgerud O, Gustafsson Liljefors M, Löhr J-M. Survival Benefits of Chemotherapy for Patients with Advanced Pancreatic Cancer in A Clinical Real-World Cohort. Cancers. 2019; 11(9):1326. https://doi.org/10.3390/cancers11091326
Chicago/Turabian StyleKordes, Maximilian, Jingru Yu, Oscar Malgerud, Maria Gustafsson Liljefors, and J. -Matthias Löhr. 2019. "Survival Benefits of Chemotherapy for Patients with Advanced Pancreatic Cancer in A Clinical Real-World Cohort" Cancers 11, no. 9: 1326. https://doi.org/10.3390/cancers11091326