Dual anti-CTLA-4 and anti-PD-1 blockade with the combination of ipilimumab (Yervoy) with nivolumab (Opdivo) induced an objective response rate (ORR) of 12% as treatment of patients with thyroid cancer, according to findings for the thyroid cancer cohort in the phase 2 SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) clinical trial (NCT02834013).1
These 2 agents have proven effective in many different tumor histologies, including subpopulations of melanoma and lung cancer, but their efficacy as treatment of rare tumors has not been determined. The study, which was presented in a poster during the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting, is a prospective, open-label, multicenter trial aimed to explore the efficacy of this combination in rare cancers.
Ipilimumab was administered intravenously (IV) at 1 mg/kg every 6 weeks plus nivolumab 240 mg IV every 2 weeks. The thyroid cancer cohort included 17 patients who were eligible and received therapy out of 21 patients who registered to this cohort. The primary end point of the study is ORR, and secondary end points include progression-free survival (PFS), overall survival (OS), stabled disease (SD) >6 months, and toxicity.
The median age of patients in the thyroid cohort was 59 years (range, 33-78), and 10 (59%) patients were male. The most common thyroid cancer subtype was papillary in 47% of patients, while other subtypes in the cohort included medullary thyroid cancer (MTC; 24%), anaplastic thyroid cancer (ATC; 24%), and Hurthle cell histology (6%).
In terms of ORR, 2 patients had a confirmed partial response (12%), which included 1 patient with PTC and 1 with ATC. One of the 4 patients with ATC had a response that lasted more than 2 years (25%). SD lasted for more than 6 months in 6 patients (35%), while 2 (12%) had SD for less than 6 months. The clinical benefit rate, which included all PRs and SD over 6 months, was 59%.
One patient with PTC who withdrew early due to toxicities, including neuropathic pain and arthralgias, had SD for more than 1 year but was not included in the response assessment.
The median PFS was 9.5 months (95% CI, 4.99-∞), and the median OS was not reached. The 6-month PFS rate was 58% (95% CI, 39-88), and the 6-month OS rate was 88% (95% CI< 74%-100%).
Overall, 94.1% of patients experienced adverse events (AEs), and 52.9% had grade 3-5 AEs. The most common AEs of any grade included fatigue in 41.2%, elevated lipase (29.4%), and acute kidney injury, diarrhea, generalized muscle weakness, anorexia, pruritis, nausea and alanine aminotransferase elevation in 21.1% each.
The most common immune-mediated AES included acute kidney injury and elevated lipase, which occurred in 29.4% of patients each. While enrolled in the study, 1 patient died.
Immunotherapy and monoclonal antibodies, such as nivolumab and ipilimumab, are suspected to assist the body’s immune system in order to attack the cancer, and these therapies may also interfere with the ability of tumor cells to grow and spread.
This combination has demonstrated its benefit with FDA approval as treatment of patients with metastatic or recurrent non–small cell lung cancer whose tumors express PD-L1 ≥1% and who do not harbor an EGFR or ALK tumor aberration. This approval was granted in May 2020 based on positive findings from the phase 3 CheckMate 227 study, which demonstrated a significant improvement in OS over chemotherapy alone.2
More recently in October 2020, the FDA also granted approval to this combination for the frontline treatment of adult patients with unresectable malignant pleural mesothelioma, which marked the first and only immunotherapy regimen indicated for the treatment of untreated, unresectable disease.3
1. Chae YK, Othus M, Patel SP, et al. A phase ii basket trial of dual anti-cdla-4 and anti-pd-1 blockade in rare tumors (DART) SWOG 1609: the thyroid tumor cohort. Poster presented at: SITC Annual Meeting. November 11-14, 2020; Virtual.
2. FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥1%) BMS [news release]. FDA. May 15, 2020. Accessed November 12, 2020. https://bit.ly/3cwvlo2
3. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) + Yervoy® (ipilimumab) as the First and Only Immunotherapy Treatment for Previously Untreated Unresectable Malignant Pleural Mesothelioma. News release. Bristol Myers Squibb. October 2, 2020. Accessed November 12, 2020. https://bwnews.pr/
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