Benefits Observed with Second-Line Therapy in Metastatic Pancreatic Cancer

Second-line treatment of metastatic pancreatic cancer, after first-line treatment with nab-paclitaxel plus gemcitabine or gemcitabine alone, is feasible and may improve outcomes, according to a post-hoc analysis of the phase 3 MPACT trial presented at the 2016 Gastrointestinal Cancers Symposium.

Greater benefit with second-line treatment was observed in MPACT patients who received first-line nab-paclitaxel plus gemcitabine, said David Goldstein, MD.

Over the past decade, treatment plans for most patients with metastatic pancreatic cancer have consisted predominantly on one line of therapy, with the utility of second-line therapy in this setting not known, said Dr. Goldstein, medical oncologist, Prince of Wales Hospital, Sydney, Australia. “We wanted to see if there was any benefit to patients being offered second-line therapy and what is the degree of benefit seen,” he said. “This has remained an uncertain area.”

The post hoc analysis of MPACT showed that in the second-line treatment setting for metastatic pancreatic cancer, “multi-agent is better than single agent for the right person, i.e, one with good performance status, low inflammation, a lower neutrophil-to-lymphocyte ratio, and a longer progression-free survival [PFS] at the end of first-line treatment,” he said. “We demonstrated that FOLFOX and FOLFIRINOX are both active after gemcitabine.”

MPACT was the pivotal phase 3 study in which nab-paclitaxel plus gemcitabine was shown superior to gemcitabine alone on all endpoints, including overall survival (OS), as first line in the treatment of metastatic pancreatic cancer.1Outcomes of patients who received second-line treatment during an observational extension of the study were evaluated.

A total of 347 (40% in each treatment arm of MPACT) patients received second-line therapy in the extension. Of these patients, 77% (132 who had received nab-paclitaxel/gemcitabine and 135 who had received gemcitabine alone in the first line) received 5-fluorouracil-based therapies or capecitabine combinations.

Patients who received second-line therapy had a better performance status at baseline compared with those not receiving second-line therapy.

The 170 patients who received nab-paclitaxel/gemcitabine followed by second-line therapy had a median OS of 12.8 months, compared with 9.9 months for the 177 patients who received gemcitabine alone followed by second-line therapy.

Some 78% and 76% of patients received a 5-FU/capecitabine-containing regimen as second-line treatment after nab-paclitaxel/gemcitabine and gemcitabine, respectively.

Among this group, median OS was significantly longer for those in the nab-paclitaxel/gemcitabine arm vs. the gemcitabine alone arm (13.5 vs. 9.5 months; P=0.012).

The 18 patients who received FOLFIRINOX following nab-paclitaxel/gemcitabine had the longest median OS at 15.7 months.

The median time from the end of first-line treatment to death for patients not receiving second-line treatment was 2.5 and 1.6 months in the nab-paclitaxel/gemcitabine and gemcitabine alone arms, respectively (HR: 0.67; P<0.001), which was less than half compared with those who received any second-line treatment (5.3 and 4.5 months, respectively).

Receiving second-line therapy was associated with longer total OS, even after adjusting for baseline charachteristics. On multivariate analysis, factors associated with longer total OS included first-line treatment with nab-paclitaxel/gemcitabine, use of second-line treatment, better Karnofsky Performance Score at baseline (90 to 100 vs. 70 to 80), no liver metastases, a neutrophil-to-lymphocyte ratio ≤5 compared with >5 (P<0.001 for each), and a lower CA19-9 at baseline (P=0.005).

On multivariate analysis, factors significantly associated with longer time to death from the end of first-line treatment were first-line treatment with nab-paclitaxel/gemcitabine, use of second-line therapy, a neutrophil-to-lymphocyte ≤5 compared with >5 at the end of first-line therapy, better Karnofsky Performance Score at the end of first-line therapy (P<0.001 for each), and PFS ≥ the median of 4.4 months vs. <4.4 months (P=0.002).

The analysis “supports the use of nab-paclitaxel/gemcitabine as an appropriate first-line therapy onto which a treatment plan can be built,” said Dr. Goldstein, who adds that a total treatment plan should now be considered when choosing initial therapy.

References

  1. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.N Engl J Med2013;369:1691-1703.
  2. Goldstein D, Chiorean EG, Tabernero J, et al. Outcome of second-line treatment (2L Tx) following nab-paclitaxel (nab-P) + gemcitabine (G) or G alone for metastatic pancreatic cancer (MPC).J Clin Oncol 2016;34(suppl 4S; abstr 333).