The addition of the immunotherapy agent Keytruda (pembrolizumab) to presurgical chemotherapy has significantly improved outcomes in patients with early triple negative breast cancer (TNBC), according to a primary analysis of the KEYNOTE-522 phase 3 clinical trial.
Two groups of patients with early stage 2 or stage 3 TNBC were examined in this analysis: one group received pre-surgical Keytruda (neoadjuvant) plus chemotherapy then chemotherapy after surgery, while the other received neoadjuvant chemotherapy plus a placebo and then chemotherapy after surgery. .
The main objectives of the study were complete pathological response, which is defined as the complete disappearance of all cancers at the time of surgery, and event-free survival. Both study endpoints were met.
“We have already shown that pathological (complete response) was positive with the addition of (Keytruda) to chemotherapy. It increased and improved pathology (complete response) from 51.2% in the control arm to 64.8% in the chemotherapy plus Keytruda arm, ”said Dr Peter Schmid, professor of cancer medicine at the Barts Cancer Institute of London, in an interview with CURE. ®.
Schmid continued, “We also presented long-term follow-up data in terms of event-free survival – the second primary endpoint – where, with a median overall survival of 39 months, we show statistically significant improvement and again. once significant for event-free survival. survival.”
The three-year event-free survival rates are approximately 60% in the Keytruda group compared to 24% in the placebo group.
Breakdown of results by cancer subtype
Keytruda works by inhibiting PD-1, a protein found in immune cells that can mask cancer cells. When the drug stops the PD-1 / PD-L1 pathway from working, it helps the patient’s immune system recognize and attack the cancer. Interestingly, however, Schmid explained that there was not much of a difference in outcomes between patients whose tumors were PD-L1 positive and PD-L1 negative.
Regarding the stage of the cancer, there was a slightly better improvement in the rates of complete pathologic response for patients with lymph node involvement compared to those without disease in their lymph nodes.
“But in terms of long-term event-free survival and reduced recurrence, we see a similar benefit whether the patients have stage 2 or 3 disease,” Schmid said.
Safety and side effects of Keytruda neoadjuvant
Immunotherapy agents like Keytruda work by activating the patient’s immune system to detect and fight cancer. In doing so, the introduction of any of these drugs may put patients at risk of developing immune system side effects, which can affect any organ system in the body.
In KEYNOTE-522, Schmid said that the side effects related to the immune system are generally manageable and that there are no new safety signals, which means new side effects of Keytruda that were not observed. previously in previous studies and patients treated with the drug.
“So overall, if we learn from the KEYNOTE-522 study that adding one year of immune therapy to primary treatment for stage 2 / stage 3 TNBC with six months of neoadjuvant chemotherapy and six months in the adjuvant setting, significant improvement in both pathologic complete response rates and, more importantly, long-term outcomes, dramatically reducing recurrence in these patients, ”Schmid concluded.
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