Atezolizumab Plus Targeted Therapies Show Promise in Anaplastic Thyroid Cancer

Atezolizumab查看药品详情, in combination with targeted therapies, has shown promising results in extending overall survival for patients with anaplastic thyroid carcinoma (搜索)搜索该疾病 (ATC), according to a phase 2 trial published in JAMA Oncology. The study (NCT03181100查看临床试验) explored the efficacy of atezolizumab (Tecentriq) combined with either vemurafenib查看药品详情 (Zelboraf) plus cobimetinib查看药品详情 (Cotellic) or bevacizumab查看药品详情 (Avastin), depending on the tumor's genetic profile.

The trial enrolled 43 patients, with 42 being evaluable, and divided them into three cohorts based on their tumor mutations. Cohort 1 included patients with mutated BRAF (搜索)搜索该靶点 V600E tumors who received vemurafenib查看药品详情/cobimetinib查看药品详情 plus atezolizumab查看药品详情. Cohort 2 comprised patients with mutated RAS (搜索)搜索该靶点 or NF1/2 (搜索)搜索该靶点 tumors treated with cobimetinib plus atezolizumab. Cohort 3 consisted of patients without any of these variants, who received bevacizumab查看药品详情 plus atezolizumab.

Survival Outcomes

Across all three cohorts, the median overall survival (OS) was 18.23 months (95% CI, 7.79-43.24), with a median follow-up time of 18.97 months (95% CI, 0.43-72.11). Specifically, cohort 1 (n = 19) achieved a median OS of 43.24 months (95% CI, 16-NE) and a median progression-free survival (PFS) of 13.93 months (95% CI, 6.60-64.13). Cohort 2 (n = 21) had a median OS of 8.74 months (95% CI, 5.13-36.96) and a median PFS of 4.80 months (95% CI, 1.84-14.69). Cohort 3 (n = 3) showed a median OS of 6.21 months (95% CI, 4.1-NE) and a median PFS of 1.3 months (95% CI, 1.3-NE). The median follow-up times for cohorts 1 and 2 were 42.14 months (95% CI, 2.66-72.11) and 8.74 months (95% CI, 0.43-55.92), respectively.

Investigator Commentary

"The genetically-matched targeted therapy plus immunotherapy combination strategy across cohorts 1 to 3 resulted in an OS of 19 months—to our knowledge the longest OS reported to date in an [anaplastic thyroid carcinoma (搜索)搜索该疾病] clinical trial, achieving the primary objective of the study," the study authors noted.

Trial Design and Patient Population

The study included patients with an ECOG performance status of 0 to 2 and adequate organ function. Patients who had previously received anti-PD1 or PD-L1 antibodies or pathway-targeting agents were excluded, but those with prior cancer history were not excluded due to the aggressive nature of ATC. Prior to treatment, an induction phase of paclitaxel (80 mg/m2) or nab-paclitaxel (125 mg/m2) was administered weekly for up to three doses to facilitate mutation-driven treatment assignment.

Adverse Events and Response Rates

Adverse events (AEs) were observed across all cohorts, including one death possibly related to trial participation due to colonic perforation in cohort 1. Other serious AEs included colitis, papilledema, retinopathy, left ventricular dysfunction, pneumonitis, pancreatitis, and esophageal perforation. The overall response rate (ORR) for cohort 1 was 50%, cohort 2 was 14%, and cohort 3 was 33%. A complete response of 5.6% was only observed in cohort 1.

Surgical Outcomes

Of the 12 patients with locoregional tumors that became resectable during treatment, 11 underwent surgery, and 8 of them are still alive. These cases included stage IVB (n=4) and stage IVC (n=8) tumors. Two patients required temporary tracheostomies and/or postoperative radiation following surgery.

Trial Adaptations

The study authors emphasized that their entry criteria were more permissive to address historical challenges in ATC trials. This included allowing patients who could not swallow pills to crush vemurafenib查看药品详情 or substitute cobimetinib查看药品详情 and permitting bridging chemotherapy.