Definitive Local Consolidative Therapy for Oligometastatic Solid Tumors: Results from the Lead-In Phase of the Randomized Basket Trial EXTEND

Purpose/Objective(s)

The benefit of local consolidative therapy (LCT) for oligometastasis across histologies is undefined. EXTernal beam radiation to Eliminate Nominal metastatic disease (EXTEND; NCT03573611) is a phase II basket trial randomizing patients with 1-5 metastatic sites to standard of care (SOC) systemic therapy with or without LCT. We hypothesized that patients treated with LCT would have superior progression-free survival (PFS). Prior to the randomization phase of this trial, we initiated a single-arm lead-in component to evaluate enrollment feasibility and identify histology baskets most likely to complete accrual. Here we report the accrual, efficacy, and toxicity results of the lead-in phase.

Materials/Methods

Eligible histologies included colorectal, sarcoma, lung, head and neck, ovarian, kidney, melanoma, pancreatic, prostate, cervix/uterine, breast, and cholangiocarcinoma. All patients were treated with SOC systemic therapy plus LCT to all sites of active metastatic disease and primary/regional disease (as applicable). Enrollment in the lead-in phase was capped after 6 months, or for an individual histology, after accrual of 8 patients with that histology. Definitive LCT included surgery or radiation. Dose, fractionation, and systemic therapy were per oncologist discretion. PFS was defined by radiographically (RECIST v1.1), biochemically (prostate only), or clinically or by death, and was estimated by the Kaplan-Meier method. Common Terminology Criteria for Adverse Events v4.0 was used.

Results

From August 2018 through January 2019, 49 patients were enrolled and received LCT. The average age was 63 (range: 32-86). Data cutoff was February 14, 2022. Thirty-six patients had progression and 13 died. The median follow-up time for censored patients was 38 months (range 16-42 months). Prostate (n=8), breast (n=8), and kidney (n=7) represented the most common histologies. Many patients had one metastasis (53%), and 86 total lesions were treated. The most common LCT modality was radiation (97%), which was typically stereotactic (63%). Local control rate was 98% (n=84/86 tumors). Median PFS time was 13 months (95% CI 9–24), and 3-year overall survival rate was 73% (95% CI 57%–83%). Most progression events were new lesions outside the irradiated field (n=30, 83%). Grade 3 toxicity rate was 4% (n=2) and no grade 4+ toxicities were observed.

Conclusion

The prospective lead-in phase of EXTEND demonstrated feasibility of rapid accrual to a multi-histology basket trial, encouraging PFS, and low rates of severe toxicity at mature follow-up. The randomized phase is ongoing with histology-based baskets, which will provide histology-specific evidence to guide the application of LCT in oligometastatic disease.