Overall Survival Prediction and Usefulness of Second-Line Chemotherapy in Advanced Pancreatic Adenocarcinoma

Vienot, Angélique; Beinse, Guillaume; Louvet, Christophe; Mestier, Louis de; Meurisse, Aurélia; Fein, Francine; Heyd, Bruno; Cléau, D.; d’Engremont, Christelle; Ac, Dupont-Gossart; Lakkis, Zaher; Tournigand, Christophe; Bouché, Olivier; Rousseau, Benoı̂t; Neuzillet, Cindy; Bonnetain, Franck; Borg, Christophe; Vernerey, Déwi

doi:10.1093/jnci/djx037

Cited by 42 publications

(50 citation statements)

References 37 publications

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“…Subgroup analysis of the patients in this study showed that a low GPS and a low CEA level were independently associated with a good outcome. Previous reports indicated that the performance status, CA19-9 level, duration of the first-line chemotherapy, and inflammation-based prognostic score were important prognostic factors in a salvage setting [25,26] [29]. It is now widely accepted that the inflammation-based prognostic score, such as the GPS, is a reliable indicator of survival for many types of malignant solid tumors including PC in various settings [11] [30].…”

Section: Discussionmentioning

confidence: 99%

Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

Sawada

Kasuga

Mie

et al. 2020

Preprint

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Purpose There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). This study aimed to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and investigate prognostic factors for survival.Methods From 2015–2019, we retrospectively reviewed the medical records of patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2,400 mg/m2 for 46 hours without bolus infusion) until disease progression, patient refusal, or unacceptable toxicity.Results In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2-9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8-5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5-100%), 77.2% (range 38.1-100%), and 85.9% (range 36.9-100%), respectively. Grade 3-4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6-16.3) and 7.6 months (95% CI 4.1-10.5) for the good prognostic factors, 6.5 (95% CI 5.5-10.0) and 3.6 months (95% CI 2.7-4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9-6.6) and 1.7 months (95% CI 0.9-4.3) for the poor prognostic factors, respectively.Conclusions The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

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Section: Discussionmentioning

confidence: 99%

Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

Sawada

Kasuga

Mie

et al. 2020

Preprint

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“…Better understanding of BTC prognosis may emerge from molecular studies [21] and also from the development of more informative databases including easily available clinicobiological parameters that were not available in our study, such as smoking status or neutrophil-to-lymphocyte ratio [22,23]. Overall, our results highlight a considerable heterogeneity in survival in patients with aBTC receiving L2, with median OS ranging from 3 to 13 months.…”

Section: Discussionmentioning

confidence: 73%

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

Neuzillet¹,

Casadei-Gardini²,

Brieau³

et al. 2019

European Journal of Cancer

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Background: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. Methods: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. Results: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N Z 392). Conclusion: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design. ª

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“…Obstructive jaundice caused by biliary tract invasion is a common complication and a negative prognosticator in pancreatic cancer patients . Early chemotherapy without optimal biliary drainage might increase chemotherapy related toxicity .…”

Section: Discussionmentioning

confidence: 99%

“…Obstructive jaundice caused by biliary tract invasion is a common complication and a negative prognosticator in pancreatic cancer patients. 24 Early chemotherapy without optimal biliary drainage might increase chemotherapy related toxicity. 25,26 Our study showed that patients presenting with obstructive jaundice had an unfavorable outcome if they receive palliative chemotherapy within 2 weeks after cancer F I G U R E 2 Kaplan-Meier curve of overall survival (A) and postchemotherapy survival (B) in patients stratified by different time interval groups diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Association of time interval between cancer diagnosis and initiation of palliative chemotherapy with overall survival in patients with unresectable pancreatic cancer

et al. 2019

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Introduction Palliative chemotherapy is the standard treatment for patients with unresectable pancreatic cancer. Whether the early initiation of palliative chemotherapy is associated with a favorable survival outcome for these patients is not known. This study aimed to analyze the association of the time interval between cancer diagnosis and initiation of palliative chemotherapy with survival outcome in patients with pancreatic cancer. Method A total of 838 patients with unresectable pancreatic cancer who underwent palliative chemotherapy from 2010 to 2016 at 4 institutions in Taiwan were retrospectively enrolled. All patients were categorized according to time interval between cancer diagnosis and initiation of palliative chemotherapy for comparison of the survival outcome. Result The median time interval was 14 days (range, 0 to 163 days) in our patient cohort. Accordingly, 22%, 29%, and 49% of the patients underwent palliative chemotherapy within 1, 1 to 2, and >2 weeks after cancer diagnosis, respectively. The survival outcome had no statistical difference among these 3 patient groups. Subgroup analyses revealed that patients with the time interval ≤2 weeks exhibited poorer survival outcome than those with the time interval >2 weeks if they initially presented with jaundice (6.1 months vs 8.4 months, P = 0.029). In contrast, patients with the time interval ≤2 weeks revealed a better survival outcome than those with the time interval >2 weeks if they initially presented with pain (8.0 vs 6.3 months, P = 0.014). Conclusion In our study, time interval between cancer diagnosis and the initiation of palliative chemotherapy >2 weeks was not associated with a poorer survival outcome for patients with unresectable pancreatic cancer. Our result might help clinicians to clarify that early initiation of palliative chemotherapy might provide survival benefit for patients who present with tumor pain, but not for those who present with jaundice.

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Overall Survival Prediction and Usefulness of Second-Line Chemotherapy in Advanced Pancreatic Adenocarcinoma

Abstract: This prognostic nomogram and score in patients with aPDAC can accurately predict OS before administration of L2 and may help clinicians in their therapeutic decisions.

Cited by 42 publications

References 37 publications

Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

Association of time interval between cancer diagnosis and initiation of palliative chemotherapy with overall survival in patients with unresectable pancreatic cancer

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