"We don't know if one is better than the other and we don't know if the combination is better, but it's the one chance we have at cure," she said. Given that patients who develop metastatic TNBC require a lifetime of chemotherapy without the possibility of cure, Nangia and her colleagues have decided to give both capecitabine and pembrolizumab to very high-risk patients. However, capecitabine wasn't used in the KEYNOTE-522 trial, making it unclear whether capecitabine, pembrolizumab, or both in combination are most effective as adjuvant treatments. Overall, patients with TNBC who received capecitabine had a 42% reduced risk of recurrence, second cancer, or death.
KEYNOTE 522 2022 TRIAL
The CREATE-X trial, which evaluated adjuvant capecitabine after neoadjuvant chemotherapy and surgery in 910 patients with HER2-negative residual invasive breast cancer, showed that not only did patients with HER2-negative residual disease benefit from capecitabine, but so did a subset of those with residual TNBC.Ī final analysis of the trial showed that for the subset of patients with TNBC, 70% of those who received capecitabine plus standard therapy after surgery remained disease-free and alive compared with only 56% of the group who received standard therapy alone. As a result, she has turned to capecitabine as a potential solution.
KEYNOTE 522 2022 HOW TO
With this indication, young women, for whom immunotoxicity is especially concerning given the life-long effects, are having to go through 5 months of heavy-duty chemotherapy and then 1 year of adjuvant pembrolizumab, she stressed.įor Julie Nangia, MD, medical director of breast oncology at the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston, her concern is how to administer pembrolizumab in patients who still have residual disease after neoadjuvant therapy. After surgery, patients were given adjuvant pembrolizumab every 3 weeks for up to nine cycles.įor years the goal has been to de-escalate treatment, explained Yuan, but now these new trial data are driving oncologists to escalate therapy by giving more chemotherapy and adding immunotherapy. Trial participants on the investigational arm received four cycles of pembrolizumab every 3 weeks in the neoadjuvant setting plus paclitaxel and carboplatin followed by an additional four cycles of pembrolizumab and then either doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. Of equal and perhaps more pressing concern is that the KEYNOTE-522 trial evaluated a "heavy duty" chemotherapy backbone in combination with pembrolizumab, a regimen that is "not easy" for patients, said Yuan. However, without a biomarker for which to select only the patients who will benefit from the addition of pembrolizumab, Yuan for now offers pembrolizumab to all patients who meet the indication criteria but remains vigilant for a more tailored approach. The trial also met its second primary endpoint, showing a relative 37% improvement in event-free survival for the pembrolizumab group versus placebo group (HR 0.63, 95% CI 0.48-0.82, P=0.00031). Yuan Yuan, MD, PhD, a medical oncologist at City of Hope in Duarte, California, says it is unclear which patients with high-risk, early-stage disease truly benefit from the addition of pembrolizumab to chemotherapy, given that more than half of patients achieve a pathological complete response (pCR) without pembrolizumab.ĭata from the randomized, phase III KEYNOTE-522 trial - which enrolled 1,174 patients with newly diagnosed, treatment-naive, high-risk, early-stage TNBC regardless of PD-L1 expression status - showed a pCR rate of 63% for patients who received pembrolizumab in combination with chemotherapy versus a rate of 56% for those who received placebo plus chemotherapy, meeting the first of the trial's primary endpoints.
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