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Sequential Therapy Boosts Survival in Metastatic Pancreatic Cancer

— Phase II study shows a 32% reduced risk of death compared with standard treatment

MedpageToday
A computer rendering of pancreatic cancer.

For patients with metastatic pancreatic ductal adenocarcinoma (PDAC), sequential treatment with nab-paclitaxel (Abraxane) plus gemcitabine followed by modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX) led to improved overall survival (OS) compared with traditional nab-paclitaxel/gemcitabine therapy, a randomized phase II study showed.

In the so-called SEQUENCE trial, the 12-month OS rate was 55.3% with sequential therapy compared with 35.4% in the control group (P=0.02), noted Alfredo Carrato, MD, PhD, of Alcalà University in Madrid, and colleagues.

The median OS was 13.2 months versus 9.7 months, respectively (HR 0.68, 95% CI 0.48-0.95), they reported in .

"The SEQUENCE trial is one of the few randomized metastatic PDAC clinical trials to report positive efficacy results in the last decade," Carrato and team wrote. "It provides evidence on the use of a new treatment strategy with full-dose sequential nab-paclitaxel-gemcitabine-mFOLFOX compared with the standard nab-paclitaxel-gemcitabine treatment in patients with performance status (ECOG [Eastern Cooperative Oncology Group] 0 to 1) and untreated metastatic PDAC."

However, the sequential strategy led to more grade 3 or higher neutropenia (47% vs 24%) and thrombocytopenia (24% vs 8%) compared with the standard treatment, as well as two treatment-related deaths compared with none.

In an , Vaibhav Sahai, MBBS, of the University of Michigan in Ann Arbor, and Al B. Benson III, MD, of Northwestern University in Chicago, called the results "intriguing," particularly since they contrasted with other published data on the impact of alternating chemotherapy regimens.

"The regimen used in SEQUENCE can be readily adapted in practice, although as more data emerge it should become more certain whether this approach leads to better outcomes," they wrote. "However, the true potential benefit of this approach still needs to be validated in a phase III trial."

The included 157 adults with histologically or cytologically confirmed stage IV PDAC without central nervous system metastasis, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, no previous systemic or investigational therapy for metastatic disease, and an ECOG performance status of 0 to 1.

They were randomly assigned to receive nab-paclitaxel plus gemcitabine on days 1, 8, and 15, followed by mFOLFOX on day 29 of a 6-week cycle, or nab-paclitaxel plus gemcitabine on days 1, 8, and 15 of a 4-week cycle.

The 24-month OS rates were 22.4% in the sequential group versus 7.6% in the control group.

The median time to progression was 9.3 months and 5.3 months, respectively (HR 0.46, 95% CI 0.32-0.67), while the median progression-free survival was 7.9 months and 5.2 months (HR 0.52, 95% CI 0.36-0.73).

The 31 patients in the sequential group who received any second-line treatment had a mean OS of 16.9 months, while the 19 patients in the control group treated with oxaliplatin-based chemotherapy in subsequent lines had a median OS of 12.3 months (HR 0.49, 95% CI 0.26-0.93)

The best confirmed overall response rate was 39.7% in the sequential group (with three complete responses) and 20.3% in the control group.

All patients in the trial experienced at least one emergent adverse event of any grade. Adverse events of grade 3 or higher for the sequential and control groups occurred in 89% and 80% of patients, with serious events in 49% and 54%, respectively.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The trial was supported by the Spanish Cooperative Group for the Treatment of Digestive Tumors through a grant provided by Celgene.

Carrato reported relationships with Baxter Healthcare Corporation, Bristol Myers Squibb, Hutchison MediPharma, Merck Sharp and Dohme, and Mylan Pharmaceuticals.

Co-authors reported multiple relationships with industry.

The editorialists reported multiple relationships with industry.

Primary Source

NEJM Evidence

Carrato A, et al "Nab-paclitaxel plus gemcitabine and FOLFOX in metastatic pancreatic cancer" NEJM Evid 2024; DOI: 10.1056/EVIDoa2300144.

Secondary Source

NEJM Evidence

Sahai V, Benson AB "Are we there yet? -- alternating chemotherapy regimens in pancreatic cancer" NEJM Evid 2024; DOI: 10.1056/EVIDe2300341.