CC patients have higher inflammation and lower testosterone, grip strength, functional status, erectile function, fat mass, and appendicular lean body mass. Inflammation, TT, and albumin are associated with heavier symptom burden in this population. Interventional trials are needed to determine whether testosterone replacement and/or antiinflammatory agents benefit cancer patients.

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Context Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti–PD-1 nivolumab. Objective The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. Design Single-arm, multicenter, phase 2 clinical trial with two-stage design. Setting Comprehensive cancer center. Patients Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. Intervention Nivolumab (240 mg) IV every 2 weeks. Results Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. Conclusion Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.

6022 Background: BRAF mutations are present in ~44% of papillary thyroid carcinoma (PTC) and its role in development of PTC is well established. We hypothesized that dabrafenib (BRAF inhibitor) would have efficacy in BRAF mutated PTC and that combining it with trametinib (MEK inhibitor) would result in greater clinical efficacy than dabrafenib alone, through vertical inhibition of the RAF/MAP/ERK pathway and mitigation of potential mechanisms of resistance. Methods: Patients (pts) with BRAF mutated radioiodine refractory PTC who had evidence of disease progression within 13 months prior were randomized to Arm A (dabrafenib 150 mg PO BID) or Arm B (dabrafenib 150 mg PO BID + trametinib 2 mg PO qd). Cross-over to Arm B was allowed at time of progression. Responses were assessed by modified RECISTv1.1 every 2 months. Primary endpoint was objective response rate (ORR) (complete-, partial- and minor-response). With assumed true ORR of 15% vs 35%; and 90% power to identify the correct regimen as most promising, 26 pts were to be accrued in each Arm. Results: In this randomized phase 2 trial, 53 pts (median age 63 years, 38 females) were enrolled; 25% of pts had 1-3 prior therapy with multi-kinase inhibitors. Median follow up was 13 months. Preliminary efficacy results are outlined in Table. The treatment-related adverse events were similar to previously reported phase III clinical trial of these drugs in melanoma. Conclusions: Single agent dabrafenib, as well as combination of dabrafenib/trametinib are well tolerated therapies that result in similar high objective response rates with durable responses in pts with progressive BRAF-mutated PTC. BRAF-pathway targeted therapies provide novel treatment options. Clinical trial information: NCT01723202. [Table: see text]

Background Lenvatinib is a multikinase inhibitor approved to treat radioiodine-refractory differentiated thyroid cancer (RR-DTC) at a starting dose of 24 mg/day. This study explored, in a double-blinded fashion, whether a starting dose of 18 mg/day would provide comparable efficacy with reduced toxicity. Methods Patients with RR-DTC were randomized to lenvatinib 24 mg/day or 18 mg/day. The primary efficacy endpoint was objective response rate as of Week 24 (ORRwk24); odds ratio noninferiority margin: 0.4. The primary safety endpoint was frequency of grade ≥3 treatment-emergent adverse events (TEAEs) as of Week 24. Tumors were assessed using RECIST v1.1. TEAEs were monitored and recorded. Results The ORRwk24 was 57.3% (95% confidence interval [CI] 46.1–68.5) in the lenvatinib 24-mg arm and 40.3% (95% CI 29.3–51.2) in the lenvatinib 18-mg arm, with an odds ratio [18/24 mg] of 0.50 (95% CI 0.26–0.96). As of Week 24, the rates of TEAEs grade ≥3 were 61.3% in the lenvatinib 24-mg arm and 57.1% in the lenvatinib 18-mg arm, a difference of −4.2% (95% CI −19.8–11.4). Conclusion A starting dose of lenvatinib 18 mg/day did not demonstrate noninferiority compared with a starting dose of 24 mg/day as assessed by ORRwk24 in patients with RR-DTC. The results represent a clinically meaningful difference in ORRwk24. The safety profile was comparable, with no clinically relevant difference between arms. These results support the continued use of the approved starting dose of lenvatinib 24 mg/day in patients with RR-DTC and adjusting the dose as necessary.