"A recent exploratory analysis of the POSEIDON study revealed an objective response rate to durvalumab plus tremelimumab plus chemotherapy of 45.2% versus 29.4% of durvalumab plus chemotherapy and 27.3% of chemotherapy alone in patients with
STK11-mutant NSCLC. The combination of chemotherapy with durvalumab and tremelimumab was also associated with significantly improved PFS (6.4 versus 4.6 mo; hazard ratio: 0.47 [95% confidence interval or CI: 0.23–0.93]) and numerically longer OS (15 versus 10.7 mo; HR: 0.56 [95% CI: 0.30–1.03]), whereas there was no clear evidence of benefit from the durvalumab-chemotherapy combination when compared with chemotherapy alone.
15
Similarly, among patients with
KEAP1-mutant NSCLC, the objective response rate to durvalumab plus tremelimumab plus chemotherapy was 45.5%, as opposed to 21.7% and 33.3% of patients receiving durvalumab plus chemotherapy or chemotherapy only, respectively. Although median PFS was similar across the three arms, median OS was numerically longer in patients receiving the triplet (13.7 mo) versus those who received durvalumab plus chemotherapy (8.1 mo) and chemotherapy alone (8.7 mo).
15
In the MYSTIC trial, there was no significant difference in median OS with durvalumab or durvalumab plus tremelimumab versus chemotherapy in patients with
STK11- and
KEAP1-mutant NSCLC, although the 2-year survival rates were generally higher with the combination.
In the CheckMate 9LA study comparing nivolumab plus ipilimumab plus 2 cycles of chemotherapy versus chemotherapy alone, patients with
STK11 and
KEAP1 mutations had improved PFS with dual checkpoint blockade versus chemotherapy (
STK11: 5.4 versus 4.2 mo, HR: 0.61 [95% CI: 0.37–1.00];
KEAP1: 8.2 versus 4.0 mo, HR: 0.34 [95% CI: 0.14–0.83]).
17 Although there was no statistically significant difference in OS between the treatment arms, OS was numerically longer in patients who received the nivolumab/ipilimumab combination with chemotherapy versus those who received chemotherapy alone."
