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ONCAlert | Upfront Therapy for mRCC

Liquid Biopsy of KRAS Predicts Survival in Advanced Pancreatic Cancer

Alice Goodman
Published Online: 4:24 PM, Wed April 22, 2015
Vlada Melnikova, MD, PhD

Vlada Melnikova, MD, PhD

A prospective study of retrospectively analyzed blood samples of patients with nonresectable pancreatic cancer found that plasma KRAS mutational burden correlates with overall survival (OS). Patients whose tumors had high levels of KRAS in their circulating tumor DNA (ctDNA) had decreased survival compared with those with low levels of KRAS. Further, combining baseline levels and ctDNA KRAS after patients had 2 cycles of treatment was a better predictor of survival than baseline ctDNA KRAS alone.

KRAS pretreatment plasma levels serve as a prognostic factor in this patient population. Monitoring KRAS levels in plasma and then combining baseline levels with longitudinal levels is a powerful predictor of overall survival,” stated coauthor of the study, Vlada Melnikova, MD, PhD, vice president for research and development at Trovagene Inc, San Diego, CA, the company developing and marketing the liquid biopsy test.

Melnikova reported results at the 2015 Annual Meeting of the American Association for Cancer Research (AACR). Archived plasma samples were prospectively collected from 182 patients with advanced or metastatic pancreatic cancer in the Danish BIOPAC study. There were 85 females and 97 males with a median age of 68 years, and all were undergoing treatment with either gemcitabine or FOLFIRINOX at the time the study was conducted.

A highly sensitive mutation enrichment assay for the detection of KRAS mutations in ctDNA was used to analyze the samples at baseline for association with OS and again for response to therapy; 640 plasma samples were collected from 182 patients. Of these, 176 patients had evaluable plasma samples at baseline.

Using a cut-off point of 5.5 copies /100,000 for low and high KRAS levels, a statistically significant negative association was found between KRAS levels and OS, showing that patients with lower KRAS levels lived longer (P <.0001).

Among patients treated with gemcitabine, those with low baseline KRAS levels had a median survival of 296 days compared with 148 days for those with high baseline KRAS levels. Among the patients who received FOLIRINOX, median survival was 499 days for those with low baseline KRAS levels and 210 days for those with high baseline KRAS levels.

KRAS mutational load in 176 patients with serially collected plasma samples was analyzed in a time-dependent manner. High KRAS counts during treatment were significantly associated with lower OS (P <.001). The strength of this association was greater for post-baseline KRAS counts than it was for baseline KRAS counts.

Combining the baseline KRAS and longitudinal KRAS data after 2 cycles of chemotherapy was an even better predictor of survival than baseline KRAS alone. Patients were divided into 4 groups:
  • those with low baseline KRAS and low longitudinal KRAS (responders);
  • those with low baseline KRAS and high longitudinal KRAS (nonresponders);
  • those with high baseline KRAS and high longitudinal KRAS (nonresponders);
  • and those with high baseline KRAS and low longitudinal KRAS (responders).
Median survival for these four groups, based on combining KRAS levels at baseline and after 2 cycles of chemotherapy, was 336 days, 252 days, 224 days, and 134 days, respectively.

“Circulating DNA KRAS in plasma can be used for prognostic purposes and for monitoring patients with pancreatic cancer, as this study shows,” said Melnikova.

The plasma test can be ordered by physicians, and it is currently reimbursable under the not-otherwise-specified (NOS) code by some insurers, according to a Trovagene representative.
Johansen JS, Vibat CRT, Hancock S, et al. Comparative levels of KRAS mutations circulating tumor DNA for association with overall survival in patients with non-resectable pancreatic cancer. Presented at the 2015 Annual Meeting of AACR. Philadelphia, PA. April 22, 2015. Abstract 5240.

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