Atezolizumab/Chemotherapy May Show Meaningful Activity in Thymic Carcinoma

"The results suggest combination therapy with atezolizumab plus carboplatin and paclitaxel might become a treatment option for patients with previously untreated advanced or recurrent thymic carcinoma," according to the study authors.

Adding atezolizumab (Tecentriq) to carboplatin/paclitaxel demonstrated clinically meaningful activity and a manageable safety profile among patients with previously untreated advanced or recurrent thymic carcinoma, according to findings from a phase 2 trial (jRCT2031220144) published in Lancet Oncology.¹

The objective response rate (ORR) was 56% (n = 27/48) based on independent central review (ICR) using RECIST v1.1 criteria, which met the trial’s primary end point (P <.0001). Additionally, the disease control rate (DCR) per ICR was 98% (95% CI, 89%-100%), and patients experienced a median target lesion change of 35.8% (IQR, 19.8%-55.5%). Investigator assessment yielded an ORR of 54% (95% CI, 39%-69%) and a DCR of 98% (95% CI, 89%-100%).

Based on ICR, the median progression-free survival (PFS) was 9.6 months (95% CI, 7.7-14.8), and the median overall survival (OS) was not reached (NR; 95% CI, 19.2 months to not estimable [NE]). The median duration of response (DOR) was 6.4 months (95% CI, 4.1-NE) per IRC assessment and 10.2 months (95% CI, 4.6-NE) based on investigator evaluation.

Regarding subsequent post-study therapy, 48% (n = 23/48) and 15% (n = 7/48) of patients received chemotherapy and radiotherapy, respectively. Lenvatinib (Lenvima) was the most common chemotherapeutic agent used in the second-line setting.

“Platinum-based chemotherapy has been recommended by the NCCN guidelines for chemotherapy-naive advanced or recurrent thymic carcinoma for more than 10 years, but its effectiveness was unsatisfactory.² Immune checkpoint inhibitor monotherapy for previously treated thymic carcinoma has shown moderate activity and promising long-term effects. However, systemic treatments are required that are more effective in more patients and have a longer lasting effect,” lead study author Takehito Shukuya, MD, from the Department of Respiratory Medicine at Juntendo University Graduate School of Medicine in Tokyo, Japan, wrote with coauthors.¹ “The results suggest combination therapy with atezolizumab plus carboplatin and paclitaxel might become a treatment option for patients with previously untreated advanced or recurrent thymic carcinoma.”

In this single-arm, multicenter phase 2 study, investigators assessed 48 patients with advanced or recurrent thymic carcinoma at 15 hospitals across Japan. Study treatment consisted of atezolizumab at 1200 mg intravenously on day 1, carboplatin area under the curve 6 mg/mL per minute intravenously on day 1, and paclitaxel at 200 mg/m² intravenously on day 1 every 3 weeks for a maximum of 6 cycles during the induction phase. Additionally, patients received atezolizumab at 1200 mg intravenously on day 1 every 3 weeks as maintenance for up to 2 years or until progressive disease or unacceptable toxicity.

The trial’s primary end point was ORR per ICR. Secondary end points included investigator-assessed ORR, DCR, PFS, DOR, OS, and safety.

Patients 20 years and older with histologically confirmed Masaoka stage III, IVA, or IVB thymic carcinoma not amenable to definitive therapy or recurrent thymic carcinoma following definitive treatment were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 or 1, 1 or more measurable lesions per RECIST v1.1 guidelines, adequate organ function, and a minimum life expectancy of 12 weeks.

The median patient age was 67.5 years (IQR, 56.5-72.5), and most were male (60%); the entire study population was Asian (100%). Additionally, most patients had an ECOG performance status of 1 (63%), prior history of smoking (54%), Masaoka stage IVB disease (52%), squamous cell carcinoma (71%), no prior radiotherapy (73%), and no prior chemotherapy (94%).

All patients (100%) experienced adverse effects (AEs) of any grade, which included peripheral sensory neuropathy (88%), alopecia (83%), and neutropenia (77%). Data showed that 75% (n = 36/48) had grade 3 or higher toxicities, with the most common including neutropenia (56%), leukopenia (33%), febrile neutropenia (23%), and maculopapular rash (13%).

AEs resulting in treatment discontinuation occurred in 6 patients due to single instances each of paralytic ileus, malaise plus peripheral sensory neuropathy, sudden death, myositis, disuse muscle atrophy, and Stevens-Johnson syndrome. Additionally, 63% (n = 30/48) of patients required reductions in chemotherapy doses. There were 8 deaths overall, with none being related to treatment.

References

1. Shukuya T, Asao T, Goto Y, et al. Activity and safety of atezolizumab plus carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma (MARBLE): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2025;26:331-342. doi:10.1016/S1470-2045(25)00001-4
2. Haddad RI, Bischoff L, Ball D, et al. Thyroid carcinoma, version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Aug;20(8):925-951. doi:10.6004/jnccn.2022.0040.