Written by Mona Khalil
A clinical trial evaluates a preoperative treatment approach; the findings do not mean chemotherapy can be eliminated or that current treatment practices should change
Results from a phase 2 clinical trial known as I-SPY2.2 showed that an experimental treatment strategy combining immunotherapy with a targeted treatment carrying a cytotoxic drug may allow some patients with high-risk breast cancer to skip certain blocks of conventional chemotherapy before surgery. However, the results did not establish the strategy’s superiority over the control group according to the study’s prespecified criterion.
The trial evaluated a combination of rilvegostomig, an experimental immunotherapy, and trastuzumab deruxtecan, an antibody–drug conjugate that targets cancer cells. The study enrolled patients with high-risk, stage II or III, HER2-negative breast cancer.
According to the study results, the analysis included 105 participants who received the experimental strategy and 77 participants in the control group. Researchers used magnetic resonance imaging (MRI) and biopsies to monitor tumour response and determine whether additional treatment blocks were needed before surgery.
The findings showed that some patients were able to proceed to surgery early, while others required additional treatment. In a subgroup of patients with immune-signature-positive tumours who achieved a pathological complete response during the treatment course, 21 participants—representing 62% of that subgroup—received only the first treatment block.
A pathological complete response means that no residual invasive cancer is found in the breast or lymph nodes at surgery. However, it does not guarantee that the disease will not recur, and the 62% figure does not represent all trial participants.
Despite these findings, the experimental strategy did not meet the prespecified criterion for superiority over the control group, as pathological complete response rates across the entire treatment course were similar between the two groups.
These results do not mean that chemotherapy can be eliminated entirely: the combination used includes a cytotoxic drug. Rather, the aim is to reduce exposure to certain blocks of conventional treatment in selected patients, depending on their response.
Regarding safety, interstitial lung disease was reported in 13 of the 105 participants who received the first treatment block, representing 12.4%, including one grade 3 case. Enrolment in the trial was also paused twice to review safety data before resuming.
The findings highlight a research approach focused on tailoring preoperative treatment to tumour response and biological characteristics, which could eventually help selected groups of patients avoid some unnecessary treatments.
Nevertheless, the strategy remains experimental, and these results alone are insufficient to change established treatment practices. Assessing its clinical value also requires long-term follow-up, including disease recurrence and survival outcomes.
This underscores the importance of determining each patient’s treatment plan in consultation with the oncology team, taking into account the tumour type, stage and characteristics, as well as the patient’s overall health. Patients should not stop or delay prescribed treatment based on preliminary clinical trial findings.
