Cabozantinib effects objective tumor responses, encouraging PFS in advanced carcinoid and pNET patients

Liz Meszaros, MDLinx

North American Neuroendocrine Tumor Society (NANETS) 10th Annual Symposium

Philadelphia, Pennsylvania, United States | October 19-21, 2017

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Philadelphia, PA, October 20, 2017—In patients with advanced carcinoid and pancreatic neuroendocrine tumors (pNET), cabozantinib may bring about both objective tumor responses and longer progression-free survival (PFS), according to study results presented at the North American Neuroendocrine Tumor Society (NANETS) 2017 Symposium.

Take-home messages

  • Cabozantinib may be efficacious in advanced carcinoid and pancreatic NETs patients.
  • In these two groups, cabozantinib brought about both objective tumor responses and longer progression-free survival.

Also, despite the need for dose reduction in most patients, treatment with cabozantinib was tolerable, concluded the researchers of this two-cohort phase 2 study.

“We conducted this study because, although there have been a lot of treatment advances in neuroendocrine tumor, there still is a need for additional therapies that help patients whose cancer is still progressing. We specifically looked at cabozantinib, which is a small molecule inhibitor of multiple receptors. It was approved in renal cell carcinoma and metastatic medullary thyroid cancer. And there was some pre-clinical work to suggest that it would also be active in neuroendocrine tumors,” said lead author Jennifer Chan, MD, MPH, medical oncologist, Dana Farber Cancer Institute, Boston, MA.

Dr. Chan and colleagues included 41 patients with progressive, well-differentiated carcinoid (median age: 63 years; 44% male; %ECOG PS 0/1=51/49) and 20 patients with pNET (median age: 55 years: 60% male, %ECOG PS 0/1=40/60). For the first six cycles, patients were re-staged after every two cycles, and thereafter, every three cycles. The primary endpoint of the study was response rate.

According to Dr. Chan, they included carcinoid patients because there is also an unmet need for new therapies in these patients.

“We wanted to include a broad population. We know that the diseases are different, so we analyzed them separately, but we wanted to evaluate the activity in both the carcinoid and pNET patients,” she explained.

In all, patients with carcinoid completed a median of 8 28-day treatment cycles, while pNET patients completed a median of 10 cycles.

Partial response was achieved in 15% of pNET patients (95% CI: 5%-36%), 75% achieved stable disease, and median progression free survival (PFS) was 21.8 months (95% CI: 8.5-32.0). Among carcinoid patients, 15% also achieved partial response (95% CI: 7%-28%), while 63% achieved stable disease, and median PFS was 31.4 months (95% CI: 8.5-NR).

At the time of this analysis, 14 patients were still on treatment. Reasons for treatment discontinuation included progression or death (51%), withdrawal of consent or investigator decision (28%), adverse events (21%), and Grade 3/4 toxicities including the following:

  • hypertension (13%)
  • hypophosphatemia (11%)
  • diarrhea (10%)
  • lymphopenia (7%)
  • thrombocytopenia (5%)
  • fatigue (5%)
  • increased lipase/amylase (7%)

Finally, researchers reported that dose reductions from the initial 60-mg dose were required in a full 81% of patients completing one or more cycles.

“There is preliminary data, based on this study, to suggest that [cabozantinib] is effective, and we’re planning to move forward with a larger phase 3 trial,” concluded Dr. Chan.

Currently, Dr. Chan and colleagues are conducting a randomized phase 3 trial to confirm the activity of cabozantinib in these patients.

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