Metastatic Pancreatic Cancer

New First-Line Standard for Metastatic Pancreatic Cancer

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Liposomal irinotecan regimen boosts outcomes, although expert expressed concern about toxicity

A four-drug chemotherapy combination coaxed a statistically significant 2-month improvement in overall survival (OS) in untreated metastatic pancreatic cancer versus a gemcitabine-containing regimen, a large randomized trial showed.

Median OS was 11.1 months with liposomal irinotecan (Onivyde), 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (NALIRIFOX) as compared with 9.2 months with gemcitabine and nab-paclitaxel (Abraxane). Median progression-free survival (PFS) increased from 5.6 months with gemcitabine/nab-paclitaxel to 7.4 months with NALIRIFOX.

All-grade, grade ≥3, and serious treatment-emergent adverse events (TEAEs) occurred in a similar proportion of patients in the two groups, reported Zev Wainberg, MD, of UCLA Medical Center-Santa Monica in California, at the ASCO Gastrointestinal Cancers Symposiumopens in a new tab or window.

“The OS and PFS benefits are generally consistent, regardless of ECOG [performance] status, region, and liver metastatic disease, and the safety profile with NALIRIFOX was manageable and consistent with the profiles of the treatment components,” said Wainberg. “These results support NALIRIFOX as a new reference regimen for the first-line treatment of patients with metastatic pancreatic cancer and, hopefully, something we can build off of in the future.”

NALIRIFOX does indeed represent a new standard of care for untreated metastatic pancreatic ductal adenocarcinoma, agreed ASCO invited discussant Laura Goff, MD, of Vanderbilt-Ingram Cancer Center in Nashville. She agreed with Wainberg and colleagues that NALIRIFOX led to clinically meaningful and statistically significant improvement in OS and PFS, and that the benefits were generally consistent.

However, Goff quibbled with the investigators’ conclusion that NALIRIFOX toxicity was manageable and consistent with known effects of the regimen’s components. Both regimens were highly toxic but with different toxicity profiles, which could factor into treatment decisions for patients who are unfit and unable to tolerate aggressive regimens, she said.

“I do feel that for fit patients, these results support NALIRIFOX as the new reference regimen for first-line treatment of metastatic pancreas carcinoma,” Goff concluded.

Gemcitabine-based therapy has remained the standard first-line therapy for metastatic pancreatic cancer for decades. Liposomal irinotecan plus 5-FU and leucovorin is approved for second-line treatment after progression with gemcitabine-containing treatment, Wainberg noted.

In a phase I/II trial,opens in a new tab or window the NALIRIFOX regimen achieved “promising” activity as second-line therapy for metastatic pancreatic cancer. The results supported the current phase III NAPOLI-3opens in a new tab or window trial to evaluate NALIRIFOX as first-line therapy for metastatic pancreatic cancer.

NAPOLI-3 involved 770 patients with untreated metastatic pancreatic cancer, randomized to NALIRIFOX or gemcitabine/nab-paclitaxel. The primary endpoint was OS. The trial had a median follow-up of 16.1 months.

The primary analysis showed that NALIRIFOX reduced the survival hazard by 17% (95% CI 0.7045-0.9881, P=0.0355). The 1.8-month difference in PFS represented a 31% reduction in the risk of disease progression or death versus the control arm (95% CI 0.5786-0.8334, P<0.0001). Objective response rate also favored the NALIRIFOX arm (41.8% vs 36.2%).

Almost 90% of patients in both treatment groups had grade ≥3 TEAEs, which were treatment-related in about 70% of cases. More than half of the patients in each arm had serious TEAEs, which were related to treatment in 26.5% of the NALIRIFOX arm and 19.0% in the control group. Fatal TEAEs occurred in about 6% of both groups and were treatment related in about 2% of each group.

Gastrointestinal TEAEs were more common with NALIRIFOX, whereas anemia and pyrexia occurred more often in the control arm.

Metastatic Pancreatic Cancer Second-Line Treatment Options: Is the Difference Only in Cost?

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Abstract

İntroduction

Although pancreatic cancer ranks seventh in cancer-related deaths, it is an extremely fatal disease, and more than 330,000 people die from this disease worldwide. Although there are many first-line treatment studies in the literature, there are almost no prospective studies regarding second-line therapy. Therefore, there is no standard approach in the second-line treatment of pancreatic cancer. We decided to conduct this study to investigate second-line treatments with problems such as cost, treatment efficacy, and toxicity.

Methods

Patients older than 18 years old who applied to Ege University Hospital medical oncology department with a diagnosis of metastatic pancreatic cancer, who received first-line chemotherapy due to their illness, and who had progressed afterwards were included in the study. The files of the patients who applied between 2013 and 2017 were examined.

Results

Our study’s primary endpoint was progression-free survival, and it was found that the median progression-free survival was 3.2 months in the Xelox patients, 3.7 months in the gemcitabine-nab paclitaxel patients, and 3.5 months in the other regimens. When the secondary endpoint was evaluated, overall survival, the median overall survival was 5.9 months in the Xelox patients, 5.3 months in the gemcitabine-nab paclitaxel patients, and 4.8 months in the other regimens.

Conclusion

As a result, second-line treatments were compared, and no statistically significant difference was found between them. For this reason, the side effects of previously used drugs and the side effects of new drugs to be used, as well as their costs, should be evaluated when choosing a treatment.

Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline

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Abstract

Purpose To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer.

Methods American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events.

Results Twenty-four randomized controlled trials met the systematic review criteria.

Recommendations A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens.