More than half the sessions at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting touched on immunotherapies, cell and gene therapies, and antibody-drug conjugates (ADCs) whereas about 10% of the content was focused on traditional modalities of chemotherapy, radiation, and surgery. Here, we report on data presented at the meeting and coming from studies regarding biomarker-guided therapies.
Breast Cancer
ESR1: Two new selective estrogen receptor degraders (SERD) and potential treatment options demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with ER+/HER2- advanced breast cancer and ESR1 mutations in as many Phase 3 clinical trials. Camizestrant reduced the risk of disease progression or death by 56% compared with the standard treatment in the SERENA-6 trial. Vepdegestrant showed a 43% reduction of the same risk when compared to fulvestrant in the VERITAC-2 trial.
Moreover, SERENA-6 is the first pivotal trial to demonstrate clinical utility of monitoring circulating tumour DNA (ctDNA) to detect the emergence of ESR1 resistance mutations and inform a switch in therapy ahead of disease progression. [Abstracts LBA4, LBA1000]
PIK3CA: In the phase 3 INAVO120 trial, the PI3K inhibitor inavolisib, in combination with palbociclib and fulvestrant, showed several benefits in patients with previously treated PIK3CA-mutated, HR+, HER2-advanced breast cancer: longer overall survival, delayed time until treatment with chemotherapy, reduced risk of death by 33% and increased objective response rate to 62.7% compared with placebo. [Abstract 1003]
Lung Cancer
EGFR (ex19del, L858R): Non–small cell lung cancer (NSCLC) and ex19del and L858R mutations of the EGFR gene are respectively type of lung cancer and biomarkers targeted in two phase 3 trials: NeoADAURA and HERTHENA-Lung02.
In the first one, the use of osimertinib before surgery, with or without chemotherapy, for the treatment of patients with stage II-IIIB NSCLC who harbour an EGFR mutation, showed statistically significant improvement in the major pathologic response (MPR) rate over chemotherapy alone.In the second one, patritumab deruxtecan (HER3-DXd), used to treat patients with EGFR-mutated advanced NSCLC following disease progression on a third-generation EGFR TKI, demonstrated statistically significant improvement in progression-free survival (PFS) when compared with platinum-based chemotherapy. [Abstracts 8001, 8506]
EGFR (exon20ins): Preliminary data from the phase 2b trial REZILIENT1 demonstrated clinically meaningful efficacy and manageable safety profile for a novel EGFR TKI, zipalertinib, in patients with EGFR exon20ins NSCLC who have received prior platinum-based chemotherapy and for those who received prior amivantamab, a significant and growing unmet need. [Abstract 8503]
ALK: The phase 2 study ALNEO, investigating activity and safety of alectinib as neoadjuvant treatment in resectable locally advanced stage III ALK-positive NSCLC, met its primary end point (MPR). The data support the ALK TKI as a “feasible peri-operative option” for this population of patients. [Abstract 8015]
Gastrointestinal Cancers
BRAF: Data updates from the phase 3 BREAKWATER trial demonstrated clinically meaningful and statistically significant progression free survival and overall survival improvements and manageable toxicities of first-line encorafenib plus cetuximab (EC) with mFOLFOX6 vs standard of care (SOC) in BRAF V600E-mutant metastatic colorectal cancer. EC+mFOLFOX6 is potentially practice changing as the new SOC. [Abstract LBA3500]
RAS/BRAF: Anlotinib added to standard chemotherapy represent a new first-line treatment option for RAS/BRAF wild-type, unresectable metastatic colorectal cancer patients. Indeed, in the phase 3 ANCHOR trial, the new VEGFR TKI plus CapeOX showed comparable progression free survival time and safety compared with bevacizumab plus CapeOX. [Abstract LBA3502]
MSI: The results of the phase 3 Check-Mate 8HW trial support the combination nivolumab (NIVO) plus ipilimumab (IPI) as a new standard of care treatment for MSI-H/dMMR metastatic colorectal cancer patients. Specifically, NIVO + IPI demonstrated superior progression free survival vs chemotherapy in first line and vs nivolumab across all lines. [Abstract 3501]
Prostate Cancers
HRR genes: The phase 3 AMPLITUDE trial supports niraparib plus abiraterone acetate and prednisone (AAP) as a potential new standard of care for patients with metastatic castration-sensitive prostate cancer (mCSPC) and germline or somatic HRR gene alterations (BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B, RAD54L). Adding the PARP-1/2 inhibitor to AAP significantly reduced the risk of radiographic progression and the risk of symptomatic progression and had a favourable effect on overall survival. [Abstract LBA5006]