Completion of Adjuvant Chemotherapy After Upfront Surgical Resection for Pancreatic Cancer Is Uncommon Yet Associated With Improved Survival

Altman, Ariella M.; Wirth, Keith; Marmor, Schelomo; Lou, Emil; Chang, Katherine; Hui, Jane Yuet Ching; Tuttle, Todd M.; Jensen, Eric H.; Denbo, Jason W.

doi:10.1245/s10434-019-07602-6

Cited by 93 publications

(94 citation statements)

References 41 publications

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“…A recent retrospective analysis of about 2500 radically operated PC showed that the small proportion of patients (about 10%) who completed the adjuvant chemotherapy protocol reported better survival outcomes (22 months) than those who partially completed the protocol (17 months) or who did not have chemotherapy (14 months). Our indirect comparison results underlined that mFOLFIRINOX has a higher discontinuation rate (trend) compared to the gem-cap combination, suggesting great benefits of mFOLFIRINOX for those selected patients able to complete the chemotherapy protocol [40], although data concerning the combination with nab/P have not yet been reported. Our analysis carried some limitations linked to the modest number of trials available with which to compare the three chemotherapeutic regimens, the enrolled populations (the gem-cap combination group had high numbers of PS1, R1, and node-positive patients; mFOLFIRINOX high CA.19 level) and the different primary endpoints (DFS/RFS/EFS for mFOLFIRINOX and gem-nab/P and OS for gem-cap).…”

Section: Discussionmentioning

confidence: 82%

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Galvano

Castiglia

Rizzo

et al. 2020

Cancers

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Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studies met the selection criteria and were included in our indirect comparison. Indirect comparisons for efficacy outcomes showed a benefit in terms of DFS (disease-free survival)/EFS (event-free survival)/RFS (relapse-free survival) for both mFOLFIRINOX versus gemcitabine+capecitabine (HR 0.69, 95% CI 0.52–0.91) and versus gemcitabine+nab/paclitaxel (HR 0.67, 95% CI 0.50–0.90). No significant advantage was registered for OS (overall survival). Indirect comparisons for safety showed an increase in terms of G3-5 AEs (with the exception of neutropenia) for mFOLFIRINOX versus gemcitabine+capecitabine (RR 1.24, 95% CI 1.03–1.50), while no significant differences were observed versus gemcitabine+nab/paclitaxel. According to our results, mFOLFIRINOX is feasible and manageable and could represent a first option for fit PC resected patients.

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Section: Discussionmentioning

confidence: 82%

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Galvano

Castiglia

Rizzo

et al. 2020

Cancers

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“…Immediate surgical resection followed by adjuvant chemotherapy has long been the standard treatment for PDAC, and recent trials suggest improving OS for those patients who are able to undergo resection and receive adjuvant therapy [4,5,38]. However, pancreatectomy is a complex, potentially morbid operation, and a significant proportion of patients are unable to receive adjuvant therapy either due to postoperative complications or poor performance status [6,7]. In addition, many patients develop rapid disease progression in the immediate postoperative period, suggesting that surgery was not only not beneficial for these patients, but potentially detrimental in delaying needed systemic therapy [39].…”

Section: Discussionmentioning

confidence: 99%

“…Adjuvant chemotherapy following surgery improves OS rates [3][4][5]. However, a significant proportion of patients are unable to initiate adjuvant chemotherapy following pancreatectomy, frequently because of postoperative complications or rapid disease recurrence [6]; many more are unable to finish the planned course of adjuvant therapy [7]. Indeed, a strategy of surgery first (SF) followed by planned adjuvant therapy has not resulted in significant improvements in OS during the past several decades, even at high-volume, experienced institutions [8,9].…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Meta-Analysis of Randomized Controlled Trials

Cloyd

Heh

Pawlik

et al. 2020

JCM

105

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The efficacy of neoadjuvant therapy (NT) versus surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. A random-effects meta-analysis of only prospective randomized controlled trials (RCTs) comparing NT versus SF for potentially resectable (PR) or borderline resectable (BR) PDAC was performed. Among six RCTs including 850 patients, 411 (48.3%) received NT and 439 (51.6%) SF. In all included trials, NT was gemcitabine-based: four using chemoradiation and two chemotherapy alone. Based on an intention-to-treat analysis, NT resulted in improved overall survival (OS) compared to SF (HR 0.73, 95% CI 0.61-0.86). This effect was independent of anatomic classification (PR: hazard ratio (HR) 0.73, 95% CI 0.59-0.91; BR: HR 0.51 95% CI 0.28-0.93) or NT type (chemoradiation: HR 0.77, 95% CI 0.61-0.98; chemotherapy alone: HR 0.68, 95% CI 0.54-0.87). Overall resection rate was similar (risk ratio (RR) 0.93, 95% CI 0.82-1.04, I 2 = 39.0%) but NT increased the likelihood of a margin-negative (R0) resection (RR 1.51, 95% CI 1.18-1.93, I 2 = 0%) and having negative lymph nodes (RR 2.07, 95% CI 1.47-2.91, I 2 = 12.3%). In this meta-analysis of prospective RCTs, NT significantly improved OS in an intention-to-treat fashion, compared with SF for localized PDAC. Randomized controlled trials using contemporary multi-agent chemotherapy will be needed to confirm these findings and to define the optimal NT regimen.been associated with improved rates of margin-negative resection and a decreased incidence of lymph node metastases [10,11]. NT also offers several other theoretical benefits, including early treatment of presumed micro-metastatic disease, enhanced selection of patients with appropriate tumor biology for surgery, and the ability to histologically measure the response to therapy [12,13]. Evidence of improved survival has also been suggested based on data from cancer databases [10], meta-analyses of retrospective studies [14], and Markov decision models [15]. In turn, NT has become the preferred approach for borderline resectable (BR) PDAC, while guidelines support the use of either SF or NT for potentially resectable (PR) PDAC [16][17][18].Despite the theoretical and empirical advantages of NT, its use in the United States has remained relatively low [19,20], potentially driven by the lack of level I evidence for its efficacy. Until recently, only two small randomized controlled trials (RCTs) had been performed comparing SF to NT, and both were terminated early due to poor accrual [21,22]. Previous systematic reviews and meta-analyses that have purported a survival benefit with NT included non-randomized prospective and retrospective studies, which are limited due to their inherent selection biases [14,[23][24][25][26]. As several larger RCTs have recently been completed, albeit with older neoadjuvant regimens, the purpose of the current study was to perform a meta-analysis limited to only RCTs evaluating SF vs. NT for PDAC.

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“…In many trials, with highly selected patients who have completely recovered from surgery, the completion rate of chemotherapy ranges from 54 to 79% [26,52]. A.M. Altman et al [58] studied the rate of completion of AC and the factors associated with completion. They collected 2440 patients who underwent upfront surgery, 65% of the patients received no AC, 28% received incomplete AC, and only 7% completed six cycle of AC [58].…”

Section: Adjuvant Treatment—the Datamentioning

confidence: 99%

Are We Sure that Adjuvant Chemotherapy is the Best Approach for Resectable Pancreatic Cancer? Are We in the Era of Neoadjuvant Treatment? A Review of Current Literature

Oneda

Zaniboni

2019

JCM

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The outcome of pancreatic cancer is poor, with a 9% 5-year survival rate. Current treatment recommendations in the 10%–20% of patients who present with resectable disease support upfront resection followed by adjuvant therapy. Until now, only early complete surgical (R0) resection and adjuvant chemotherapy (AC) with either FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) or nab-paclitaxel plus gemcitabine have been shown to prolong the survival. However, up to 30% of patients do not receive adjuvant therapy because of the development of early recurrence, postoperative complications, comorbidities, and reduced performance status. The aims of neoadjuvant chemotherapy (NAC) are to identify rapidly progressing patients to avoid futile surgery, eliminate micrometastases, increase the feasibility of R0 resection, and ensure the completion of multimodal treatment. Neoadjuvant treatments are effective, but there is no consensus on their use in resectable pancreatic cancer (RPC) because of its lack of a survival benefit over adjuvant therapy. In this review, we analyze the advantages and disadvantages of the two therapeutic approaches in RPC. We need studies that compare the two approaches and can identify the appropriate sequence of adjuvant therapy after neoadjuvant treatment and surgery.

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Completion of Adjuvant Chemotherapy After Upfront Surgical Resection for Pancreatic Cancer Is Uncommon Yet Associated With Improved Survival

Cited by 93 publications

References 41 publications

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Meta-Analysis of Randomized Controlled Trials

Are We Sure that Adjuvant Chemotherapy is the Best Approach for Resectable Pancreatic Cancer? Are We in the Era of Neoadjuvant Treatment? A Review of Current Literature

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