Targeted Treatment Provides ORR and PFS Benefit in Pretreated Metastatic Solid Tumors

Targeted treatment as determined by mutational status was associated with a benefit in overall response rate (ORR) and progression-free survival (PFS) vs standard of care (SOC) in pretreated patients with metastatic solid tumors, according to data from the phase 2 ROME trial (NCT04591431) that were presented at the 2024 ESMO Congress.

“Historically, drug approval has been based on tissue-specific model, initially guided by histology and later also molecular biomarkers; however, [it is] associated only with specific cancer site. More recently, the tumor-agnostic model, driven by specific genomic alteration regardless of the tumor site, has been applied for the progress of several drugs,” Andrea Botticelli, MD, said in a presentation of the data. “The mutational model guided by compressive genomic profiling and molecular tumor board activities could adapt to overcome some limitation of previous models and allow for the selection of more effective targeted therapies.”

Botticelli is a member of the Department of Medical Oncology at Sapienza Universita di Roma in Rome, Italy.

The trial included 400 patients and a representation of 38 different tumor types. The most common cancers were colorectal (16%), breast (10%), gastric (9%), glioblastoma (9%), and biliary tract (9%). All patients had metastatic disease and were pretreated with 1 to 2 lines of therapy. They were randomly assigned 1:1 to undergo comprehensive genomic profiling via FoundationOne CDx and LiquidCDx followed by molecular tumor board discussion or SOC. Crossover due to disease progression or unacceptable toxicity was allowed.

“The role of molecular tumor board was to combine all the available information, both clinical information and genomic information in order to define the most effective and safe therapy or combination strategy,” Botticelli said.

The most common targetable genomic alterations were hTMB (high tumor mutational burden; 34%), PIK3CA/AKT/PTEN (19%), ERBB2 (14%), FGFR (8%) and microsatellite instability (MSI; 4%). The most commonly prescribed targeted therapies were ipilimumab (Yervoy) plus nivolumab (Opdivo; 37%); ipatasertib (16%); pemigagatinib (Pemazyre; 8%); T-DM1 (Kadcyla; 8%) and atezolizumab (Tecentriq) plus ipatasertib (6%).

Findings showed that ORR was 17.0% in the targeted treatment arm, compared with 9.5% in the SOC arm (P = .026).

The median PFS was 3.7 months and 2.8 months in the targeted and SOC arms, respectively (HR 0.64; 95% CI, 0.51-0.80; P < .001). Additionally, the 12-month PFS rate was 22%% in the targeted treatment group compared with 7% in the SOC group.

Regarding survival, the median OS was 9.2 months vs 7.6 months, respectively (HR 0.89; 95% CI, 0.68-1.13; P = .299).

“The HR was 0.89, and the P value was not statistically significant. However, 52% of patients in the SOC group were treated with targeted therapy in the crossover phase,” Botticelli explained.

The study authors also conducted an exploratory analysis of patients with hTMN/MSS disease. The targeted therapy group was treated with immunotherapy and had a median PFS of 3.6 months and a 12-month PFS rate of 32.7%. Meanwhile, in the SOC cohort, the median PFS was 2.8 months with a 12-month PFS rate of 6.3% (HR 0.65; 95% CI, 0.42-0.92; P = .01).

The rate of grade 3 or higher adverse effects was lower in the targeted treatment arm compared with the SOC arm, at 35% and 40%, respectively.

Reference

Botticelli A, Scagnoli A, Conte P, et. al. The Rome trial from histology to target: The road to personalize targeted therapy and immunotherapy. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. LBA7.