Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study
Abstract Background Gemcitabine/erlotinib treatment offers limited benefit in unselected patients with pancreatic ductal adenocarcinoma (PDAC). Development of skin rash has been associated with favorable outcomes in patients treated with gemcitabine/erlotinib. This study aimed to extend knowledge on...
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| Language: | English |
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BMC
2020-02-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-020-6636-7 |
| _version_ | 1818294360668635136 |
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| author | C. Benedikt Westphalen Tobias Kukiolka Benjamin Garlipp Lars Hahn Martin Fuchs Peter Malfertheiner Marcel Reiser Fabian Kütting Volker Heinemann Andreas Beringer Dirk T. Waldschmidt |
| author_facet | C. Benedikt Westphalen Tobias Kukiolka Benjamin Garlipp Lars Hahn Martin Fuchs Peter Malfertheiner Marcel Reiser Fabian Kütting Volker Heinemann Andreas Beringer Dirk T. Waldschmidt |
| author_sort | C. Benedikt Westphalen |
| collection | DOAJ |
| description | Abstract Background Gemcitabine/erlotinib treatment offers limited benefit in unselected patients with pancreatic ductal adenocarcinoma (PDAC). Development of skin rash has been associated with favorable outcomes in patients treated with gemcitabine/erlotinib. This study aimed to extend knowledge on the effectiveness of gemcitabine/erlotinib in metastatic PDAC in the context of clinical practice and with focus on skin rash. Methods This multicenter, non-interventional study enrolled 376 patients with metastatic PDAC receiving gemcitabine/erlotinib. The primary endpoint was overall survival (OS) in patients with skin rash versus no skin rash. Secondary endpoints included progression-free survival (PFS), treatment satisfaction and safety. All data were analyzed using descriptive statistics. Survival time and time to disease progression were estimated using the Kaplan-Meier method. Effectiveness endpoints were analyzed for subgroups by skin rash grade (no rash, rash grade 1, rash grade ≥ 2), duration of erlotinib treatment (≤8 weeks, > 8 weeks), Eastern Cooperative Oncology Group (ECOG) performance status at baseline (0–1, 2) and age (≤65 years, > 65 years). Results Within the full analysis set (FAS; N = 270), 48 patients (17.8%) developed grade 1 rash, 51 patients (18.9%) grade ≥ 2 rash, while 171 patients (63.3%) did not develop a rash. Median OS of all patients was 9.11 months with an OS of 9.93 months in rash-positive and 8.68 months in rash-negative patients. Median PFS was 5.06 months for rash-positive and 4.11 months for rash-negative patients. PFS was longer in patients with rash grade ≥ 2 and in older patients (> 65 years). Examination using a multivariate Cox proportional model revealed that an age > 65 years was associated with longer OS (hazard ratio 0.640; p = 0.0327) and PFS (hazard ratio 0.642; p = 0.0026). Out of the 338 patients in the SAF, 310 patients (91.7%) experienced at least one AE, and 176 patients (52.1%) experienced skin-related side effects, all of which were CTC grade 1 to 3. Conclusions Comparing rash-positive with rash-negative patients showed no significant difference in survival. While patients with rash grade ≥ 2 and older patients (independent of skin reactions) showed longer PFS, this did not translate into prolonged OS. The study did not reveal new safety signals. Trial registration ClinicalTrials.gov Identifier: NCT01782690, retrospectively registered on 4 February 2013. |
| first_indexed | 2024-12-13T03:30:31Z |
| format | Article |
| id | doaj.art-0484dbc7c1e94e40ba3604fe80c2ce56 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T03:30:31Z |
| publishDate | 2020-02-01 |
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| series | BMC Cancer |
| spelling | doaj.art-0484dbc7c1e94e40ba3604fe80c2ce562022-12-22T00:01:10ZengBMCBMC Cancer1471-24072020-02-012011810.1186/s12885-020-6636-7Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center studyC. Benedikt Westphalen0Tobias Kukiolka1Benjamin Garlipp2Lars Hahn3Martin Fuchs4Peter Malfertheiner5Marcel Reiser6Fabian Kütting7Volker Heinemann8Andreas Beringer9Dirk T. Waldschmidt10Comprehensive Cancer Center Munich & Department of Medicine III, University Hospital, LMU MunichDepartment of Medicine I, University HospitalDepartment of Surgery, Otto-von-Guericke University MagdeburgDOKUSAN GmbH & CO. KGMunich Municipal Hospital Group GmbHUniversity Hospital MagdeburgPIOH Praxis Internistischer Onkologie und HämatologieDepartment of Gastroenterology and Hepatology, University of CologneComprehensive Cancer Center Munich & Department of Medicine III, University Hospital, LMU MunichRoche Pharma AGDepartment of Gastroenterology and Hepatology, University of CologneAbstract Background Gemcitabine/erlotinib treatment offers limited benefit in unselected patients with pancreatic ductal adenocarcinoma (PDAC). Development of skin rash has been associated with favorable outcomes in patients treated with gemcitabine/erlotinib. This study aimed to extend knowledge on the effectiveness of gemcitabine/erlotinib in metastatic PDAC in the context of clinical practice and with focus on skin rash. Methods This multicenter, non-interventional study enrolled 376 patients with metastatic PDAC receiving gemcitabine/erlotinib. The primary endpoint was overall survival (OS) in patients with skin rash versus no skin rash. Secondary endpoints included progression-free survival (PFS), treatment satisfaction and safety. All data were analyzed using descriptive statistics. Survival time and time to disease progression were estimated using the Kaplan-Meier method. Effectiveness endpoints were analyzed for subgroups by skin rash grade (no rash, rash grade 1, rash grade ≥ 2), duration of erlotinib treatment (≤8 weeks, > 8 weeks), Eastern Cooperative Oncology Group (ECOG) performance status at baseline (0–1, 2) and age (≤65 years, > 65 years). Results Within the full analysis set (FAS; N = 270), 48 patients (17.8%) developed grade 1 rash, 51 patients (18.9%) grade ≥ 2 rash, while 171 patients (63.3%) did not develop a rash. Median OS of all patients was 9.11 months with an OS of 9.93 months in rash-positive and 8.68 months in rash-negative patients. Median PFS was 5.06 months for rash-positive and 4.11 months for rash-negative patients. PFS was longer in patients with rash grade ≥ 2 and in older patients (> 65 years). Examination using a multivariate Cox proportional model revealed that an age > 65 years was associated with longer OS (hazard ratio 0.640; p = 0.0327) and PFS (hazard ratio 0.642; p = 0.0026). Out of the 338 patients in the SAF, 310 patients (91.7%) experienced at least one AE, and 176 patients (52.1%) experienced skin-related side effects, all of which were CTC grade 1 to 3. Conclusions Comparing rash-positive with rash-negative patients showed no significant difference in survival. While patients with rash grade ≥ 2 and older patients (independent of skin reactions) showed longer PFS, this did not translate into prolonged OS. The study did not reveal new safety signals. Trial registration ClinicalTrials.gov Identifier: NCT01782690, retrospectively registered on 4 February 2013.http://link.springer.com/article/10.1186/s12885-020-6636-7Pancreatic ductal adenocarcinomaGemcitabineErlotinibOverall survivalProgression-free survivalSkin rash |
| spellingShingle | C. Benedikt Westphalen Tobias Kukiolka Benjamin Garlipp Lars Hahn Martin Fuchs Peter Malfertheiner Marcel Reiser Fabian Kütting Volker Heinemann Andreas Beringer Dirk T. Waldschmidt Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study BMC Cancer Pancreatic ductal adenocarcinoma Gemcitabine Erlotinib Overall survival Progression-free survival Skin rash |
| title | Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study |
| title_full | Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study |
| title_fullStr | Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study |
| title_full_unstemmed | Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study |
| title_short | Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib – results from a non-interventional multi-center study |
| title_sort | correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib results from a non interventional multi center study |
| topic | Pancreatic ductal adenocarcinoma Gemcitabine Erlotinib Overall survival Progression-free survival Skin rash |
| url | http://link.springer.com/article/10.1186/s12885-020-6636-7 |
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