乌鸦传媒

SEATTLE -- Three-fourths of patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remained on treatment 2 years after switching from octreotide (Sandostatin LAR) to lanreotide (Somatuline), a retrospective study of therapeutic transitioning showed.

The transition occurred after a median duration of 38 months on octreotide, and 67 of the 91 patients included in the analysis remained on lanreotide after a median follow-up of 24.7 months. The 91 patients had a median progression-free survival (PFS) of 23.7 months following the transition.

About a third of the patients (28/91) had clinically defined progressive disease (CDPD) at transition, which was associated with a median PFS of 15.2 months. An additional 22 patients had CDPD while on lanreotide.

In general, symptom control and adverse events remained stable or improved after the transition, reported David Ray, PharmD, of Ipsen Pharmaceuticals in Paris, at the North American Neuroendocrine Tumor Society (NANETS) annual symposium.

"Our study suggests that patients with locally advanced or metastatic GEP-NETs previously treated with long-acting octreotide monotherapy can be safely transitioned to lanreotide monotherapy," Ray concluded. "The clinical PFS observed among patients who had either non-progressive or progressive disease at the time of transition from long-acting octreotide to lanreotide reinforces the possibility of sequencing lanreotide after long-acting octreotide."

Another company-sponsored analysis of 273 patients with advanced NETs showed a median overall survival (OS) exceeding 12 years following first-line therapy, which was a somatostatin analog (SSA) in most cases. And a third NANETS report, an economic analysis, suggested lanreotide is not a cost-effective first-line option for metastatic pancreatic NETs.

Sequencing Data Needed

Despite widespread use of SSAs in the management of GEP-NETs, limited data exist regarding outcomes of patients switched from octreotide to lanreotide, Ray's group noted in a poster presentation. The analysis included adults with advanced or metastatic GEP-NETs treated at six U.S. centers and transitioned from octreotide to lanreotide, with a minimum treatment duration of at least 90 days with each drug.

Medical records showed the 91 patients initiated octreotide an average of 17 months after diagnosis and remained on the drug for an average of 38.4 months. The most commonly cited reasons for transition were disease progression (22%), formulary change (15.4%), and patient preference (9.9%). No reason could be identified in 36.3% of cases.

At the time of transition, 52 (57.1%) patients had non-progressive disease and 28 (30.8%) had CDPD. Disease status was unknown or not specified for the remaining patients.

At last follow-up, 67 (73.6%) patients remained on lanreotide, with a treatment duration ranging from 16.7-59.9 months. Of the 22 patients who had CDPD after transition, disease progression was determined by imaging in all but two cases.

In general, symptom control improved from diagnosis to initiation of octreotide and again after transition to lanreotide. The proportion of patients without symptoms was 16.5% before SSA treatment, 20.9% with octreotide, and 25.3% with lanreotide. Rates of adverse events were similar during treatment with the two SSAs. The proportion of patients without adverse events were 41.8% with octreotide and 42.9% with lanreotide.

Ray and colleagues acknowledged several limitations of the study: patient selection by convenience sample, variable approaches to assessment of tumor status, and progression defined by clinical assessment in addition to tumor imaging.

Long-Term Treatment, Survival

A multicenter "real-world" analysis of treatment patterns for advanced gastrointestinal (GI)-NETs confirmed that SSAs remain widely used and that most patients remain on treatment for long periods of time, reported Matthew H. Kulke, MD, of Boston Medical Center, and colleagues. The 273 patients included in the analysis had advanced, well-differentiated (grade 1/2) GI-NETs. Date at diagnosis ranged from March 1987 to May 2017.

Two-thirds of the patients had functional NETs at diagnosis. The primary site was the ileum in 57% of cases.

Almost 90% of the patients received octreotide alone or in combination as initial therapy. Other first-line treatments included liver-directed therapy and chemotherapy. No patient received lanreotide as initial therapy, as the drug did not have FDA approval for much of the study period, the investigators noted.

Patients started on octreotide had a median treatment duration of 12.0 years and a range of 0.2 to 20.7 years. The median time to discontinuation of first-line treatment was 154 months, including 144.5 months for octreotide. That compared with a median time to discontinuation of 3.8 months for patients who started with chemotherapy.

Median OS was 151.8 months (28% of patients died during follow-up), including 179 months for patients treated with octreotide.

Study limitations included reliance on medical records; inability to distinguish between short- and long-acting octreotide; data from cancer referral centers, which might not be applicable to other practice settings; and lack of information about care provided outside the six participating centers.

Cost-Effectiveness

The featured abstract session at NANETS included a cost-effectiveness analysis of initial versus delayed lanreotide for treatment of metastatic enteropancreatic NETs. Such analyses can help inform clinical decision-making, given the National Comprehensive Cancer Network's recent inclusion of affordability as a consideration in choosing among treatment regimens for cancer, noted James Barnes, MD, of the Palo Alto VA Medical Center in California.

Using data from the previously reported , Barnes' group developed a Markov model to evaluate the cost-effectiveness of initial treatment of lanreotide as compared with initial active surveillance and lanreotide deferred until disease progression. Barnes said the investigators based survival curves for active surveillance on outcomes of patients who crossed over to lanreotide during the extension phase of the trial. CLARINET had a primary endpoint of PFS and showed no difference in survival between the randomized groups.

To perform the cost-effectiveness analysis, investigators used the Medicare payment of $7,078 per month as the cost for lanreotide. The outcome was an incremental cost-effectiveness ratio (ICER), represented as quality-adjusted life years (QALYs). Barnes said the ICER was derived from the difference in cost between the two treatment options, divided by the difference in QALYs for the two options.

A QALY of 1 represents perfect quality of life and 0 represents death. Most analyses yield values between the two, Barnes noted.

The definition of an "acceptable" cost per QALY varies, he added. In general, the definition of acceptable cost ranges from $50,000 to $150,000 per QALY gained, depending on the source. In addition to the Medicare price for the drug, investigators used published information relevant to QALYs (0.771 QALY prior to progression, 0.612 QALY for progressed disease).

The analysis showed that upfront lanreotide resulted in 0.37 additional QALYs at a cost of $161,037, or $435,000 per QALY gained, considerably higher than the generally accepted definitions of cost-effective, said Barnes.

The investigators performed an alternative analysis that incorporated a "relaxed" assumption of similar survival between the two patient groups. With the alternative model, upfront lanreotide resulted in 0.74 additional QALYs, decreasing the cost per QALY gained to $238,000, still exceeding the generally accepted definitions.

To meet the $100,000 willingness-to-pay threshold, the monthly cost of lanreotide would have to decrease to the range of $2,000-$2,900, said Barnes. To meet the $150,000 threshold, the price would have to decline to a range of $2,800-$4,400.