A phase II study of nivolumab (N) plus ipilimumab (I) in radioidine refractory differentiated thyroid cancer (RAIR DTC) with exploratory cohorts in anaplastic (ATC) and medullary thyroid cancer (MTC).

Abstract

6513 Background: Treatment options for aggressive TC are limited. Pre-clinical data suggests efficacy of CTLA-4 plus PD-1 blockade in aggressive RAIR TC. Methods: This investigator initiated phase II study tested N (3mg/kg every 2 weeks) plus I (1mg/kg every 6 weeks) until disease progression or completion of 24 mo of treatment in RAIR differentiated TC including poorly differentiated TC (PDTC) with exploratory cohorts in anaplastic (ATC) and medullary TC (MTC). Radiographic response rate by RECIST v1.1 (CR+PR) was primary endpoint. At least 6 pts with disease response among n=32 DTC provided 84% power to distinguish between a 10% and a 25% RR (one-sided 9% binomial test). Results: Accrual is complete with n=32 patients with DTC, 10 with ATC and 7 with MTC enrolled between October 2017 and May 2019. Thirty-two DTC included: n=17 papillary, n=7 Hurthle, n=4 follicular TC, n=4 PDTC. Among n=49, median (range) age was 65 (30-88), 51% (25/49) were female. To date, in DTC, 3/32 achieved a PR (n=2 Hurthle and n=1 PDTC), 9.4% RR (.95CI:2%-25%). One near complete response has been observed. Among pts w ATC, 3/ 10 profound PR by RECIST occurred (30% RR, .95CI: 7%-65%). Among them, two remain without clear evidence of disease at 26 and 13 mo after treatment start. No PR's were observed in MTC. Most frequent grade 3-4 TRAEs were as expected and included increased lipase (n=8), increased serum amylase (n=4). There was an unexpected number of treatment related adrenal insufficiency (AI) (n=4) which was associated with long PFS (range 10.1—16.4+mo). Conclusions: N+I appears to have considerable activity in ATC. In unselected RAIR DTC, activity was low but responses were seen in PDTC and Hurthle cell TC. Exceptional responses with prolonged remissions were observed. Clinical trial information: NCT03246958 .

Immune Checkpoint Inhibitors: New Weapons Against Medullary Thyroid Cancer?

“…The present study status is classified as "Active, not recruiting". As above reported, very preliminary results of this trial have been recently published recently (26).…”

“…Very preliminary results of a phase II trial evaluating nivolumab plus ipilimumab in patients with aggressive thyroid cancer (NCT03246958) are also available (26). Indeed, 7 patients with progressive MTC and prior TKI failure were included in an exploratory cohort of the study and assessed for radiographic response based on RECIST v1.1 criteria.…”

Nihilism No More: The 2021 ATA Anaplastic Thyroid Cancer Guidelines

“…Immune checkpoint inhibitor therapy has transformed the field of oncology; antibodies targeting programmed cell death 1 (PD-1) and its ligand PD-L1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) are now FDA-approved for numerous cancer types. Emerging data suggest that ATC is rather susceptible to immunotherapy (3)(4)(5). Currently, PD-1 inhibition has been tested with some success, resulting in a 19% response rate for ATC patients.…”

Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy

“…In the PD-L1 positive population, the 1-year survival was 52.1% [133]. In addition, the combination of nivolumab and ipilimumab seems to be active in ATC with 3 out of 10 patients showing long-term major partial response in a phase II trial with 49 thyroid cancer patients [115].…”

“…Further research is required and a phase II clinical trial is ongoing (NCT02628067). ICIs combinations, such as nivolumab and ipilimumab, ICIs and TKIs combination, such as pembrolizumab plus lenvatinib, have been analyzed in different thyroid cancer cohorts showing modest increase of antitumoral activity in DTC [115,116]. Other combinations are under research.…”