Long-term somatostatin analog therapy of acromegaly following transsphenoidal surgery: efficacy and safety

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 88-129-Acromegaly & Prolactinoma
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-100
Lisa B Nachtigall*1, Arezoo Haghshenas2, Adnan Ajmal2, Nicholas A Tritos1, Brooke Swearingen3, Anne Klibanski1 and Karen Klahr Miller1
1Massachusetts General Hospital/Harvard Medical School, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Massachusetts Gen Hosp, Boston, MA
Background: The efficacy and safety of somatostatin analogs (SA) for treatment of acromegaly has been well described, but long-term data are limited. When surgery does not result in cure, many patients require pharmacologic therapy indefinitely. Thus, the effects of chronic SA therapy are important to determine.

Goal: The goal of this study is to characterize efficacy and safety of long-term SA treatment in a large patient cohort following non-curative surgical therapy for growth hormone (GH) secreting adenomas vs. a non-SA treated comparison group.

Methods:  Patients with pathologically and biochemically confirmed acromegaly who received ≥ 6 months of SA, or surgery and ≥ 6 months of post-operative follow up, were selected for inclusion (N=199, of 350 screened). The following groups were compared: 1) SA group: received SA post non-curative pituitary surgery for ≥ 6 and up to 240 months (N=127) vs. 2) Non-SA group: s/p surgery alone or surgery plus non-SA medical therapy followed for a comparable interval (N=72).

Results:  Age (45 ± 1 vs. 45 ± 2 years) (mean±SEM), baseline IGF-1 index (IGF-1 level/upper limit of normal)(2.0 ± 0.1 vs. 2.0 ± 0.1, p=NS) and sex (64% vs. 52% women, P=NS) were comparable in the SA vs. non-SA group. Baseline was defined as pre-operative for the non-SA group and post-operatively but before SA initiation for the SA group. 39% of SA vs. 17% of non-SA group (P <.002) had a history of radiation therapy (RT). 1% of the non-SA group received pegvisomant ever and 17% received cabergoline ever, compared to 34 and 47%, respectively in the SA group, P< .001. Prevalence of normal IGF-1 level was higher in the non-SA vs. SA group at 6 months (94% vs. 57%, P<.0001), 12 months (83% vs. 63%, P< .02) and 24 months (92% vs. 69%, P< .003), but did not differ at 5-10 years (93% vs. 86%, P=NS) or >10 years (94% vs. 93%, P=NS). Excluding RT and other medications, 44% of the SA group had decreased tumor size at last follow up (80 ± 4 months) compared to post-operative baseline. Percent with tumor growth did not differ between groups (7% SA vs. 10% non-SA, P=NS). Symptomatic gallstones occurred more often in women vs. men (17% vs. 5%, p< .03) but was not different between groups (15% vs. 6%, P =NS). The prevalence of pre-existing DM was 17% vs. 7%, P=NS, in SA vs. non-SA group. No one with preexisting DM in either group required additional DM medications after treatment; 38% decreased or discontinued DM medications while receiving SA vs. 80% in the surgery alone group, P=NS at last follow up (mean 77 ± 9 months). 11% in the SA group developed DM vs. 8% in the non-SA group, P=NS.

Conclusion: SA responders who remain on long-term SA therapy achieve a similar degree of IGF-1 control as those surgically cured at 5 and ≥ 10 years, with few side effects and high rates of tumor shrinkage, even after excluding RT and non-SA medication use. Pre-existing DM may resolve and often improves in patients with acromegaly treated with long-term SA therapy after surgery.

Disclosure: LBN: Researcher, Ipsen. NAT: Clinical Researcher, Ipsen. Nothing to Disclose: AH, AA, BS, AK, KKM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Investigator Iniated Award; Ipsen; grant # 218334 awarded to LBN