The original presentation of the data demonstrated a significant prolongation of the primary endpoint, PFS, in the lanreotide arm. The current subset analysis focused on 91 patients with pancreatic neuroendocrine tumors, a group of patients not studied in the PROMID trial.
For this group, median PFS was increased in the lanreotide arm compared to placebo at borderline statistical significance (median not reached vs. 12.1 months in placebo; HR 0.58.). Given that this group of patients was not studied in the PROMID trial, the current results support use of lanreotide in pNET.
Whether lanreotide is globally superior to sandostatin LAR for GEP NETs is unclear without a head to head comparison, and either is a reasonable treatment option for these patients.
Finally, Chen and colleagues presented an expanded analysis of the NAPOLI-1 trial, which randomly assigned patients with metastatic pancreatic cancer who were previously treated with gemcitabine to 5-fluorouracil with leucovorin (5-FU/LV), liposomal irinotecan (MM-398), or the combination.
While prior presentations had focused on the intent-to-treat population, this updated analysis focused on a prespecified subgroup of patients treated with at least 80% of the target dose in the first 6 weeks and without violating inclusion/exclusion criteria (137/417 patients). Results were quite similar, noting an improved survival in the combination arm (8.9 mmonths vs. 5.2 months, HR 0.57, P=0.011).
Thus, it is likely MM-398 will be approved for the treatment of gemcitabine-refractory pancreatic cancer with 5-FU/LV. Since few patients had received prior irinotecan, the relative efficacy to MM-398 to irinotecan and whether it has efficacy in irinotecan-refractory patients is unclear.
Given the high prevalence of this disease, the colorectal cancer day always generates a high level of excitement. Ng and colleagues on behalf of the Alliance presented an analysis of vitamin D levels and relationship to survival from the 80405 study.
The results of the study as a whole were first presented by Alan Venook at the 2014 American Society of Clinical Oncology Annual Meeting, demonstrating no difference in overall survival whether patients with KRAS wild-type metastatic colorectal cancer received cetuximab or bevacizumab with their initial chemotherapy.
In the current analysis, those patients in the highest quintile of plasma 25(OH)D levels had significantly improved OS compared to those in the lowest (median 32.6 months vs. 24.5 months, HR 0.67, P=0.002).
Further, increasing concentrations of 25(OH)D were associated with improved PFS (median 12.2 months vs. 10.1 months, HR 0.80, P trend=0.02).
These results were consistent across patient subtypes. There was plenty of debate outside the lecture hall about whether clinicians should be checking vitamin D levels routinely and/or supplementing levels for those who are low.
At the current time, there are no prospective data regarding vitamin D supplementation and trials are ongoing. While the data clearly tell us that higher vitamin D levels are associated with better outcomes in patients with metastatic colorectal cancer receiving initial chemotherapy, cause and effect is unclear.
Finally, Dr. Tabernero presented data from the RAISE study, a randomized phase 3 comparison of FOLFIRI plus ramucirumab vs. FOLFIRI plus placebo as second-line therapy for patients with metastatic colorectal cancer. Over 1,000 patients were randomly assigned.
The results demonstrated improved clinical outcome for the addition of ramucirumab in terms of the primary endpoint of overall survival (median 13.3 months vs. 11.7 months for placebo, HR 0.84, P=0.02) and PFS (median 5.7 months vs. 4.5 months for placebo, HR 0.79, P=0.0005). Response rates were similar at approximately 12% to 13%.
As expected, grade 3 or higher neutropenia and hypertension were increased in the ramucirumab arm. A lively discussion ensued regarding the potential place for this agent in the armamentarium of second-line mCRC. To date, bevacizumab beyond progression has demonstrated a similar improvement in survival in the second-line and is commonly used in the clinic.
The anti-VEGF fusion molecule ziv-aflibercept has also shown benefit, although it is less commonly used in the clinic since its approval is also in second-line where bevacizumab is commonly utilized. Now, we have similar data with ramucirumab.
On balance, most left the session acknowledging that ramucirumab is active in second-line mCRC, but wondering if there is a niche for it given the widespread use of bevacizumab in this setting. Cost considerations of the agents may also be a factor in choosing therapy.