Helpful Markers for Immunotherapy Response May Lie With Mutations, irAEs

Immune-related adverse events (irAEs) may help predict survival outcomes in patients with non–small cell lung cancer (NSCLC), according to research presented at the 2020 World Conference on Lung Cancer Singapore.

Additionally, patients with STK11 mutations tended to have shorter progression-free survival (PFS) than those with wild-type STK11. In patients who presented with KRAS mutations, STK11 mutations also correlated with a lower 12-month overall survival (OS) rate.

The investigators analyzed the outcomes of patients with stage IIIB to IV NSCLC who were tested for the STK11 mutation and treated with immune checkpoint inhibitors between July 2014 and November 2019. In addition to determining the role of STK11 mutations and if the occurrence of irAEs predicted immunotherapy response, the authors aimed to determine the incidence of STK11 mutations and irAEs among Hispanic and non-Hispanic patients.

The study population included 96 patients with wildtype SKT11 and 31 with an SKT11 mutation, with both groups having a median age of 65 years at diagnosis. Forty-eight patients experienced an irAE (median age, 70 years) and 77 patients were irAE negative (median age, 66 years). Overall, there were 30 Hispanic patients involved: 8 harbored the SKT11 mutation, and 14 experienced an irAE.

Outcomes in STK11-Mutant Versus -Wildtype Tumors

Median OS was higher in patients with wildtype STK11 compared with STK11-mutant tumors (12.1 months vs 8.6 months, respectively; P = 0.03). Twelve-month OS rates were also higher in the wildtype group (73% vs 55%; P = .03). Patients with a wildtype STK11 did have a slightly higher median PFS (6.3 months vs 5.6 months) and 12-month PFS rate (45% versus 43%), though these findings were not statistically significant (P = .35 and P = .85, respectively).

When it came to STK11 and KRAS mutations together, patients with wildtype STK11 had a higher rate of OS at 12 months than those with the STK11 mutation (70% vs 40%, respectively, P = .03).

However, the OS findings were not statistically significant (11.4 months vs 5.3 months; P = .13), nor were PFS findings in the KRAS-mutant group. Median PFS in the SKT11-wildtype group was 5.1 months and was 3 months in the SKT11 group.

Immune-Related Adverse Event Outcomes

Patients who experienced an irAE had statistically significantly better PFS and OS outcomes.

The average PFS was 9.5 months in those who had an irAE compared with 4.4 months in those who did not (P = .005). The PFS rate at 12 months was also better in those who had an irAE than those who didn’t (60% vs 33%, respectively; P = .0001).

When it came to OS, the median was 14.2 months in the irAE-positive group and 7.3 months in the irAE-negative group (P < .001). The rate of OS at 12 months was also higher in the group who had an irAE, at 85%, compared with 60% in those who did not (P = .00008).

The most common irAEs were hypothyroidism (35.7% of Hispanics vs 14.7% of non-Hispanics), rash (21.4% vs 29.4%), and pneumonitis (7.1% vs 5.9%).

The authors note the results indicate that the occurrence of irAEs may be useful in identifying possible responders to therapy. Therefore, they ask providers to monitor and manage those events carefully to maximize whatever benefits may come from therapy while also reducing risks.

They also mentioned that their findings should be further evaluated in larger studies in the future.

Reference:

Raez Le, Uba R, North A, et al. STK11/LKB1, KRAS mutations and immune-related adverse events as predictors of response to immunotherapy in lung cancer. Presented at: 2021 World Conference on Lung Cancer Singapore, January 28-31, 2021.