Nov 2023: Pembrolizumab (Keytruda, Merck) wurde von der Food and Drug Administration (FDA) als neoadjuvante Behandlung in Kombination mit einer platinhaltigen Chemotherapie und als postoperative adjuvante Behandlung für resektable nicht-kleinzellige Lungenkrebstumoren (NSCLC) zugelassen 4 cm oder mehr Durchmesser, in Kombination mit einer platinhaltigen Chemotherapie.
KEYNOTE-671 (NCT03425643), a multicenter, randomized, double-blind, placebo-controlled trial involving 797 patients with AJCC 8th edition resectable Stage II, IIIA, or IIIB NSCLC who had not been previously treated, assessed the drug’s efficacy. Patients undergoing platinum-based chemotherapy were randomized (1:1) to receive pembrolizumab or a placebo every three weeks for four cycles (neoadjuvant treatment).
Subsequently, for a maximum of thirteen cycles (adjuvant treatment), patients were administered either continued single-agent pembrolizumab or a placebo every three weeks. The surgical window and chemotherapy specifics are available at the link to the drug label above.
Die primären Endpunkte der Wirksamkeit waren das vom Prüfer beurteilte ereignisfreie Überleben (EFS) und das Gesamtüberleben (OS). Das mediane OS für diejenigen, die Placebo erhielten, betrug 52.4 Monate (95 %-KI: 45.7, NE) und wurde im Pembrolizumab-Arm nicht erreicht (95 %-KI: nicht schätzbar [NE], NE]; p-Wert = 0.0103). Das Risikoverhältnis [HR] betrug 0.72 [95 %-KI: 0.56; 0.93]; p-Wert=0.0103]. Das mittlere EFS im Placebo-Arm betrug 17 Monate (95 %-KI: 14.3; 22.0) im Vergleich zu 17 Monaten im Pembrolizumab-Arm (95 %-KI: 34.1 Monate, NE) (HR 0.58 [95 %-KI: 0.46; 0.72]); p-Wert=0.0001).
The adverse reactions most frequently reported by 20% or more of the patients in KEYNOTE-671 were as follows: nausea, fatigue, neutropenia, anaemia, constipation, decreased appetite, decreased white blood cell count, musculoskeletal pain, rash, congestion, vomiting, diarrhoea, and dyspnea.
A comparatively lower rate of adverse reactions prevented surgery for 6% of patients in the pembrolizumab arm who received neoadjuvant treatment, as opposed to 4.3% in the placebo arm. In addition, 3.1% of patients who received neoadjuvant treatment and surgery in the pembrolizumab arm experienced surgical delays as compared to 2.5% in the placebo arm. The safety information pertaining to the neoadjuvant and adjuvant phases can be found in the drug label link provided above.
Pembrolizumab wird in einer Dosierung von 200 mg alle 3 Wochen oder 400 mg alle 6 Wochen verschrieben. Bei Verabreichung am selben Tag wie die Chemotherapie sollte Pembrolizumab vorher verabreicht werden.
