LBA45 - Randomized open label phase III study comparing the efficacy and safety of everolimus followed by chemotherapy (CT) with streptozotocin (STZ)-5FU upon progression or the reverse sequence, in advanced progressive panNETs: The SEQTOR study (GETNE 1206)

Background

STZ-5FU and everolimus are frontline treatments in patients (pts) with advanced and progressive pancreatic panNETs. Switching between both upon progression is a common strategy, but the best sequence is not yet well established.

Methods

SEQTOR trial aims to compare the progression-free survival rate to 1st treatment (PFS1) at 12 months (m) in STZ-based CT vs Everolimus. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), median PFS1 (mPFS1) and PFS to 2nd treatment (PFS2), safety and correlatives studies. Pts with advanced WHO grade 1/2 panNETs, ECOG 0-2, were randomized 1:1 to everolimus 10 mg/day followed by STZ-5FU upon progression (arm A), or the reverse sequence (arm B). STZ-5FU was given as per Moertel or Uppsala regimens. Initial results of 12m PFS1, ORR and safety are presented.

Results

A total of 141 pts were randomized (71 vs 70 for arm A/B). Median age was 58 years (range: 33-83), and 85 (60%) were male. Overall, 20 (14%) pts were WHO G1, 113 (80%) G2, and 8 (5.7%) unknown. ORR to 1st treatment assigned was 11% vs 30% in arms A/B, respectively (p=0.014). Stable Disease was the most common outcome to the 1st treatment with a CBR of 92% and 80% for arms A/B, respectively (p=0.07). The estimated Kaplan Meier 12m PFS1 rate was 69% and 64% in arms A/B, respectively; mPFS1 was 21.5 m (95% CI: 16.9-31.3) and 23.8 m (95% CI: 13.6-30.8) in arms A/B, respectively (p=0.351). The most frequent grade 3-4 adverse events were fatigue (10%), diarrhea (7%) and abdominal pain (7%) in arm A, and fatigue (13%), neutropenia (9%) and abdominal pain (8%) in arm B. Grade 3-4 pneumonitis was 1.5% in both arms. Arm A resulted in a significant increase of any-grade rash (27% vs 8%), infections (15% vs 5%) and lung infection (15% vs 5%).

Conclusions

Both sequential strategies showed similar efficacy, with no significant differences in PFS1. STZ-5FU assigned as the 1st treatment achieved a statistically significant higher ORR than everolimus, suggesting STZ-5FU should be the 1st option when tumor shrinkage is a priority. The differences in safety profile may also inform treatment choice for selected pts.

Clinical trial identification

EudraCT: 2013-000726-66; NCT02246127.

Editorial acknowledgement

We acknowledge MFAR Clinical Research staff for their assistance in the development of this abstract.

Legal entity responsible for the study

Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).

Funding

GETNE through industry partners Novartis Pharmaceuticals.

Disclosure

R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Bayer, BMS, HMP, Ipsen, Merck, Midatech, MSD, Novartis, Pharma Mar, Pierre Fabre, Servier; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Other, Other, Honoraria received by spouse for advisory board or invited speaker roles: Abbie, AstraZeneca, Bayer, Boehringer, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. H.J. Klumpen: Financial Interests, Institutional, Invited Speaker, current treatments of cholangiocarcinoma: Medtalk; Financial Interests, Institutional, Invited Speaker, PODCAST on treatment of HCC: CCO; Financial Interests, Institutional, Advisory Board: Janssen, AstraZeneca; Financial Interests, Institutional, Invited Speaker, IMBRAVE 050: ROCHE; Financial Interests, Institutional, Invited Speaker, FIGHT 302: INCYTE; Financial Interests, Institutional, Invited Speaker, LEAP 012: MSD; Financial Interests, Institutional, Invited Speaker, TAS120: Taiho; Financial Interests, Institutional, Invited Speaker, COMPETE, COMPOSE: ITM Solucin GmbH; Financial Interests, Institutional, Invited Speaker, KEYNOTE 966: MSD; Financial Interests, Institutional, Invited Speaker, COSMIC 312: Exelixis; Other, Other, Subdomain leader G5.1: EURACAN; Other, In the Netherlands: Member National Guideline committee for biliary tract cancer; Other, in the Netherlands: Member of the National guideline committee for HCC. All other authors have declared no conflicts of interest.