Presence of Mutations and Emergence of irAEs May Correlate With I/O Response in NSCLC

Better survival outcomes may occur in patients with non-small cell lung cancer (NSCLC) who experience immune-related adverse events (irAEs), but the presence of certain mutations may interfere with survival , according to research presented at the 2020 World Conference on Lung Cancer.¹

The analysis specifically showed that patients with STK11 mutations tended to have a shorter progression-free survival (PFS) than those who had STK11 wildtype. In patients who presented with KRAS mutations, STK11 mutations also correlated with a lower 12-month overall survival (OS) rate.

The researchers analyzed the outcomes of patients with stage 3b/4 NSCLC who were tested for the STK11 mutation and were treated with immune checkpoint inhibitors between July 2014 and November 2019. In addition to determining the role of STK11 mutations and if occurrence of irAEs predicted immunotherapy response, the authors also wanted to determine the incidence of STK11 mutations and irAEs among Hispanic and non-Hispanic patients.

The study population included 96 patients who were SKT11 wildtype and 31 with an SKT11 mutation, both groups had a median age of 65 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.

STK11-Mutant Versus SKT11 Wildtype Outcomes

Median OS was higher in STK11 wildtype patients than it was in STK11-mutant patients (12.1 months versus 8.6 months, respectively; P= 0.03). Twelve-month OS was also higher with the wildtype group (73% versus 55%; P=0.03). Patients with an STK11 wildtype did have a slightly higher median PFS (6.3 months versus 5.6 months) and 12-month PFS (45% versus 43%), though those findings were not statistically significant (P=0.35 and P=0.85, respectively).

When it came to STK11 and KRAS mutations together, patients with STK11 wildtype had a higher rate of 12-month OS than those with the STK11 mutation (70% versus 40%, respectively, P=0.03).

However, the OS findings were not statistically significant (11.4 months versus 5.3 months; P=0.13), nor were PFS findings in the KRAS-mutant group. Median PFS in the SKT11 wildtype group was 5.1 months and in the SKT11 group was 3 months.

Immune-Related Adverse Event Outcomes

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

Average PFS was 9.5 months in those who had an irAE, compared to 4.4 months in those who did not (P=0.005). Twelve-month PFS was also better in those who had an irAE than those who didn’t (60% versus 33%, respectively; P=0.0001).

When it came to OS, average OS was 14.2 months in the irAE-positive group and 7.3 months in the irAE-negative group (P<0.001). Twelve-months OS was also higher in the group who had an irAE, at 85%, compared to those who did not, 60% (P=0.00008).

The most common irAEs were hypothyroidism, which was experienced by 35.7% of Hispanic irAE-positive patients and 14.7% of non-Hispanic irAE patients; rash (21.4% and 29.4%); and pneumonitis (7.1% and 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.}