1202P - Final analysis of TENEC trial: A phase II trial of temozolomide (TMZ) as second-line treatment for advanced neuroendocrine carcinomas (NEC) in patients (pts) with a poor performance status (PS)

Background

There is no consensus on the second-line regimen for pts with progressive NEC. These patients (pts) generally have poor performance status (PS) and low tolerance to combination therapy. Metronomic TMZ showed, in retrospective trials, a good safety and efficacy profile. This trial aims to assess the efficacy of TMZ given every other week in pts with advanced platinum-pretreated grade 3 (G3) poorly-differentiated neuroendocrine neoplasms (NEN) and NEC.

Methods

TENEC is an open-label, non-randomized, phase II trial that recruited pts with platinum-pre-treated metastatic neuroendocrine carcinoma. Pts received 75 mg/m²/day of TMZ for 7 days followed by 7 days of no treatment (regimen 1 week on/1 week off). The primary endpoint was the overall response rate (ORR) analysed by the Kaplan-Meier method. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and tolerability.

Results

From 2017 to 2020, 38 pts were enrolled. The median age of enrolled pts was 61.5 years (25–77). Two pts (5.3%) had an Eastern Cooperative Oncology Group (ECOG) PS score of 0, 58% had an ECOG PS score of 1, 34% had an ECOG PS score of 2 and 3% had an ECOG PS score of 3. Among the pts with determined Ki67, 33.3% had a Ki67 index <55%, and 66.6% had Ki67 index ≥55%. Thirteen pts (34%) had metastases in a single site, 12 pts (31%) had two different sites of metastasis, and six pts (15%) had metastases in three or more sites. ORR was 18%, including one complete response and six partial responses. The median PFS was 6.5 months (95% CI: 5.1–14.5), and the median OS was 12 months (95% CI: 5.6–20.8). The 1-year PFS rate was 37%. No statistically significant difference in median OS (p=0.81, hazard ratio [HR] 95% CI: 0.5–1.9) and median PFS (p=0.85, HR 95% CI: 0.4–2) was observed among pts with Ki67 <55% vs ≥55%. Nausea, diarrhoea and abdominal pain were the most common adverse.

Conclusions

One-week-on/one-week-off TMZ shows promising activity in pts with NEN G3 and NEC. The excellent safety profile confirmed the possibility of using this scheme in pts with poor performance status. Randomised trials are warranted to confirm treatment benefits showed in this trial.

Clinical trial identification

EudraCT 2016-005238-31; NCT04122911.

Editorial acknowledgement

Legal entity responsible for the study

Salvatore Tafuto.

Funding

Has not received any fundingˆ.

Disclosure

C. von Arx: Financial Interests, Personal, Advisory Board, Receipt of consultation fees:Participation in a company sponsored speaker’s bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, Gentili, Lilly, Novartis, Ipsen; Financial Interests, Personal, Other, Conference Fee and travel grant: Organon; Financial Interests, Personal, Other, Conference fee and travel grant: AAA. All other authors have declared no conflicts of interest.