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First-Line Immune Checkpoint Inhibitor Monotherapy vs Chemoimmunotherapy in Advanced NSCLC According to KRAS Variant Status


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In a study reported in a research letter in JAMA Oncology, Sun et al found that first-line immune checkpoint inhibitor monotherapy was associated with better overall survival among patients with advanced non–small cell lung cancer (NSCLC) with PD-L1 expression ≥ 50% and KRAS variant vs KRAS wild-type disease. No difference in survival was observed according to KRAS status with first-line chemoimmunotherapy.

As stated by the investigators, “To our knowledge, no prior studies have evaluated the association of KRAS status with outcomes following immune checkpoint inhibitor monotherapy vs chemoimmunotherapy in patients with PD-L1 expression of 50% or greater.”

Our findings suggest that among patients with PD-L1 expression of 50% or greater NSCLC treated with immune checkpoint inhibitor monotherapy, KRAS wild-type is associated with worse survival compared with KRAS variant.
— Sun et al

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The study involved data from the Flatiron Health database on 1,127 patients with nonsquamous NSCLC with PD-L1 expression ≥ 50%; known KRAS variant status; and no alteration in EGFR, ALK, or ROS1 who were treated with first-line immune checkpoint inhibitor monotherapy or chemoimmunotherapy between January 2016 and May 2020.

Key Findings

Among the 1,127 patients, 573 (50.8%) had KRAS variants and 554 (49.2%) had wild-type KRAS. Patients with KRAS variants were more likely to be female (58.7% vs 47.1%, P = .002) and to have a history of smoking (96.4% vs 87.7%, P < .001). No significant differences in other characteristics—including age, race/ethnicity, performance status, and stage at diagnosis—were observed.

Among 705 patients receiving first-line immune checkpoint inhibitor monotherapy, 363 had KRAS variants and 342 had KRAS wild-type. Among 412 receiving first-line chemoimmunotherapy, 210 had KRAS variants and 212 had KRAS wild-type.

Among patients treated with immune checkpoint inhibitor monotherapy, median overall survival for those with KRAS variant status vs KRAS wild-type status was 21.1 vs 13.6 months (P = .03), with the association remaining significant on adjusted analysis (adjusted hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.61–0.98). Among patients treated with chemoimmunotherapy, median overall survival for those with KRAS variant vs KRAS wild-type status was 20.0 vs 19.3 months (P = .93; adjusted HR = 0.99, 95% CI = 0.70–1.40).

Among all patients with KRAS variant status, median overall survival among those treated with immune checkpoint inhibitor monotherapy vs chemoimmunotherapy was 21.1 vs 20.0 months (P = .78, adjusted HR = 1.03, 95% CI =0.75–1.40). Among all patients with KRAS wild-type status, median overall survival was 13.6 with immune checkpoint inhibitor monotherapy vs 19.3 months with chemoimmunotherapy (P = .06; adjusted HR = 1.19, 95% CI = 0.89–1.58).

The investigators concluded, “Our findings suggest that among patients with PD-L1 expression of 50% or greater NSCLC treated with immune checkpoint inhibitor monotherapy, KRAS wild-type is associated with worse survival compared with KRAS variant. In contrast, survival did not differ appreciably between patients with KRAS variant and KRAS wild-type status who were treated with chemoimmunotherapy.”

They continued, “Whereas patients with PD-L1–high NSCLC with KRAS variant had favorable survival (median overall survival ≥ 20 months) with either immune checkpoint inhibitor monotherapy or chemoimmunotherapy, patients with KRAS wild-type who were treated with immune checkpoint inhibitor monotherapy had numerically inferior survival compared with those treated with chemoimmunotherapy, although this difference was not statistically significant. These data suggest that chemoimmunotherapy might be favored over immune checkpoint inhibitor monotherapy for patients with KRAS wild-type with high PD-L1 expression.”

Charu Aggarwal, MD, MPH, of the University of Pennsylvania Abramson Cancer Center, Division of Hematology/Oncology, is the corresponding author for the JAMA Oncology article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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