Patients with metastatic solid tumors who underwent comprehensive genome profiling to determine the best targeted treatment strategy tended to have improved outcomes compared with those who received standard of care, according to findings from the phase 2 ROME trial presented at the 2024 European Society for Medical Oncology Congress.
Per the National Cancer Institute, the cancer genome describes the DNA, gene expression, proteins and molecular features of cancer cells. Now, cancer therapies exist that target certain cancer cell characteristics, so by knowing about the genome, clinicians can more accurately predict which treatment regimens may be most successful for an individual patient.
Study Highlights:
- Targeted therapy based on genomic profiling can improve outcomes for patients with metastatic solid tumors.
- Patients who underwent comprehensive genome profiling and targeted therapy had higher response rates, longer progression-free survival, and longer overall survival compared to those who received standard of care.
- Immunotherapy showed promising results for patients with high tumor mutational burden (hTMB).
- Targeted therapy was generally well-tolerated with fewer severe side effects compared to standard of care.
“The mutational model guided by comprehensive genomic profiling and molecular tumor board activities could adapt to overcome some limitation of previous [treatment] models and allow for the selection of more effective targeted therapies,” study author, Dr. Andrea Botticelli of the Sapienza Universita di Roma in Rome, Italy, said in a presentation of the findings.
Four hundred patients were involved in the study: 200 were randomly assigned to undergo targeted therapy as determined by comprehensive genomic profiling and discussions from a molecular tumor board of experts, while the other 200 underwent standard of care. The most common cancer type in the study population was colorectal (16%), followed by breast (10%), gastric (9%), glioblastoma (9%) and biliary tract cancers (9%).
“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 explained.
The most frequently occurring targetable genomic alterations (specific cancer characteristics that have drugs available to target them) were: hTMB (34%), PIK3CA/AKT/PTEN (19%), ERBB2 (14%), FGFR (8%) and MSI (4%). The following targeted therapies were prescribed: Yervoy (ipilimumab) plus Opdivo (nivolumab), which was prescribed to 37% of patients in the genome-tested group; ipatasertib (16%); Pemazyre (pemigatinib; 8%); Kadcyla (T-DM1; 8%); and Tecentriq (atezolizumab) plus ipatesertib (6%).
Findings showed that the overall response rate (ORR; percentage of patients whose disease shrunk or disappeared after treatment) was 17% in the targeted treatment group, compared with 9.5% in the standard-of-care group.
Average progression-free survival (PFS), which describes the time patients live without their disease getting worse, was 3.7 months and 2.8 months in the targeted treatment and standard-of-care group, respectively. At 12 months, PFS rates were 22% and 7% for those who had targeted therapy an those who had standard of care, respectively.
Further, median overall survival (OS), which tracks how long patients live before death of any cause, was 9.2 months versus 7.6 months in the targeted and standard-of-care groups, respectively. The 12-month OS rates were 41.5% and 38%. OS results, however, were not statistically significant, meaning that the researchers could not say for sure that one treatment method is better than the other. Additionally, 52% of patients in the standard-of-care group crossed over to the targeted treatment group.
The researchers also conducted an exploratory analysis of patients with a hTMB/microsatellite stable disease receiving immunotherapy as a targeted treatment. The median PFS in this group was 3.6 months, with a 12-month PFS rate of 32.7%. This was better than the standard-of-care group that had a median PFS of 2.8 months and a 6.4% 12-month PFS.
Study data also showed that the incidence of severe or worse (grade 3 or higher) side effects was lower in the targeted therapy group at 35%, compared to 40% for the standard care group.
“The ROME trial demonstrated that a mutational-based treatment approach based on the (Molecular Tumor Board) discussion of (comprehensive genomic profiling) results may significantly improve ORR and PFS compared to (standard of care) in pretreated patients with metastatic solid tumors, particularly with immunotherapy,” the researchers wrote in their abstract.
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