A less intensive regimen of nab-paclitaxel (Abraxane) plus gemcitabine appears to be as efficacious as the standard regimen in first-line treatment for metastatic pancreatic cancer, but less toxic and far less expensive, according to a study that earned a Merit Award at the 2015 Gastrointestinal Cancers Symposium in San Francisco.1 The modified regimen, adopted by oncologists at The Ohio State University, Columbus, combines gemcitabine at 1,000 mg/m2 and nab-paclitaxel at 125 mg/m2 every 2 weeks.
“Chemotherapy is administered on days 1 and 15 of a 28-day cycle, eliminating day 8 dosing. Granted, this is a retrospective study and the numbers are small, but overall the modified regimen looks equivalent to outcomes from the MPACT trial, and the toxicity looks significantly better,” said Kavya Krishna, MBBS, a third-year oncology fellow at the University.
MPACT Trial
The phase III MPACT trial established the benefit of the gemcitabine/nab-paclitaxel regimen after showing a modest improvement in overall survival, vs gemcitabine alone, as first-line treatment.2 The standard regimen gives gemcitabine at 1,000 mg/m2 and nab-paclitaxel at 125 mg/m2, both administered on days 1, 8, and 15 of a 28-day cycle. In MPACT, only 71% of the nab-paclitaxel doses and 63% of the gemcitabine doses remained at full dose due to protocol-driven reductions secondary to toxicities. One-quarter of patients required growth factors, and 17% had grade 3 or higher neuropathy.
“Based on our interpretation of the data and on data suggesting that biweekly administration of gemcitabine-based chemotherapy combinations preserves efficacy, with improved toxicity profile, we adopted a modified regimen,” she said.
Retrospective Analysis
Dr. Krishna presented a retrospective analysis of a prospectively established database of patients who received the modified regimen first-line between April 1, 2013, and August 31, 2014. Sixty-three patients were evaluable for toxicity, and 47 were evaluable for response.
Patients on the modified regimen had a median progression-free survival of 4.8 months (95% confidence interval [CI] = 2.6–7.4) and median overall survival of 11.1 months (95% CI = 5.3–not reached). In MPACT, the median progression-free survival was 5.5 months in the nab-paclitaxel/gemcitabine group and 3.7 months in the gemcitabine group, and median overall survival was 8.5 months and 6.7 months, respectively.
With the modified regimen, 27% of patients experienced neurotoxicity of any grade, with the rate of grade 3 or 4 toxicity less than 2%. The rate of grade 3 or 4 neutropenia was 10%, and growth factor support was required in only 8% of the patients, compared with 26% from the MPACT trial.
Cost Savings
The Ohio State University investigators teamed up with Daniel A. Goldstein, MD, of Emory University School of Medicine, Atlanta, to determine the cost savings, which they figured at $3,000 per patient per month, compared to standard gemcitabine/nab-paclitaxel. When taking into account other costs such as growth factor utilization, the savings amounts to $5,500 per month.
“Growth factor support is also a major driver of costs at $3,369 per dose,” noted Dr. Goldstein, “but there is no clear guidance as to who should receive it. The precise reporting of growth factor usage is variable between trials.”
In a comparison of several regimens for metastatic pancreatic cancer, Dr. Goldstein reported at the meeting that the standard gemcitabine/nab-paclitaxel regimen was the most expensive regimen.3
“Our objective was to analyze the costs of first-line regimens to further aid in decision-making and develop a platform upon which to assess value,” said Dr. Goldstein. “We calculated the monthly cost for multiple standard regimens: gemcitabine, FOLFIRINOX [leucovorin, fluorouracil, irinotecan, oxaliplatin], and gemcitabine/nab-paclitaxel. We also calculated the cost for two novel regimens that have demonstrated good efficacy—modified-schedule gemcitabine/nab-paclitaxel and carboplatin/paclitaxel—in pancreatic cancer.”
With these chemotherapy regimens, median overall survival ranged from 6 to 11 months. FOLFIRINOX and modified gemcitabine/nab-paclitaxel had the highest median overall survival at 11.1 months, while gemcitabine alone had the lowest at 6.7 months.
The monthly cost of the regimens (combining drug costs, administration costs, and costs for grade 3/4 adverse events) and their associated median overall survival were as follows: gemcitabine/nab-paclitaxel, $12,221 (8.5 months, phase III data); FOLFIRINOX, $7,234 (11.1 months, phase III data); modified gemcitabine/nab-paclitaxel, $6,716 (11.1 months, retrospective study); carboplatin/paclitaxel, $2,154 (8.9 months, phase III data); single-agent gemcitabine, $1,363 (6.7 months, several phase III trials).
“Health-care systems have finite resources, so there is increasing emphasis on metrics to define value in health care,” Dr. Goldstein commented. “These data provide useful financial information to incorporate into the decision-making process for both clinicians and policymakers.” ■
Disclosure: Drs. Krishna and Goldstein reported no potential conflicts of interest. For full disclosures of all study authors, view the abstracts at meetinglibrary.asco.org.
References
1. Krishna K, et al: 2015 Gastrointestinal Cancers Symposium. Abstract 366. Presented January 16, 2015.
2. Von Hoff DD, et al: N Engl J Med 369:1691-1703, 2013.
3. Goldstein D, et al: 2015 Gastrointestinal Cancers Symposium. Abstract 368. Presented January 16, 2015.
