PRRT (177Lu-DOTATATE) with capecitabine and temozolomide (CAPTEM)

The Australasian Gastrointestinal Trials Group CONTROL NET study (Pavlakis et al.) is a randomised, open-label phase 2 trial that tested 177Lu-octreotate PRRT combined with capecitabine plus temozolomide (CAPTEM) against PRRT alone (midgut NET cohort) or CAPTEM alone (pancreatic NET, pNET, cohort). Chemoradionuclide therapy is given on the premise that temozolomide's DNA-alkylating damage is potentiated by concurrent radiation, an approach analogous to the CAPTEM regimen already used as chemotherapy alone in NETs.

In the pNET cohort, PRRT/CAPTEM produced a numerically longer median progression-free survival (not reached versus 14 months for CAPTEM alone) and a higher objective response rate (44% versus 28%, and in an earlier interim readout 67% versus 33%). In the midgut NET cohort the two regimens performed similarly on the 15-month progression-free survival endpoint (90% for PRRT/CAPTEM versus 92% for PRRT alone), with a numerically higher objective response rate for the combination (31-34% versus 15-23%) but at the cost of roughly double the grade 3/4 haematological toxicity (88% versus 46%).

The trial's own conclusion is that CAPTEM/PRRT activity in pNETs is durable enough to justify phase 3 testing, while in midgut NETs the extra toxicity did not appear matched by extra benefit. This is consistent with a wider literature (systematic review, PMC9790144) reporting CAPTEM alone achieves roughly 77% disease control across NET subtypes, most convincingly in pancreatic disease, and with retrospective comparisons finding broadly similar progression-free survival between PRRT and CAPTEM given sequentially rather than together.