KRAS wild-type status linked to shorter OS with immunotherapy alone in lung cancer subset
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Patients with KRAS wild-type, PD-L1-high non-small cell lung cancer treated with immunotherapy alone exhibited considerably shorter OS than those with a KRAS mutation, according to results in a research letter published in JAMA Oncology.
However, researchers did not observe significant differences in OS between patients with vs. without a KRAS mutation who received a combination of immunotherapy and chemotherapy.
“Clinicians can currently use immunotherapy either alone or in combination with chemotherapy for patients with PD-L1-high NSCLC. This decision is often made based on clinical factors including disease burden, symptoms and comorbidities,” Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence in the hematology-oncology division at Perelman School of Medicine at University of Pennsylvania, and a HemOnc Today Editorial Board Member, told Healio. “However, KRAS and other biomarkers do not currently have an established role in helping to choose between immune checkpoint inhibitor-based monotherapy and chemotherapy plus immune checkpoint inhibitor therapy.”
Aggarwal and colleagues examined whether treatment outcomes differed by KRAS status among 1,127 patients with advanced nonsquamous NSCLC and PD-L1 expression of 50% or greater treated between January 2016 and May 2020 with first-line immunotherapy alone or in combination with chemotherapy. Researchers obtained patient data from the Flatiron Health database and used Kaplan-Meier methods to compare OS between treatment groups stratified by treatment type and KRAS status.
Overall, 50.8% of patients had KRAS variant status. These patients were more likely than those with KRAS wild-type status to be female (58.7% vs. 47.1%; P = .002) and have a history of smoking (96.4% vs. 87.7%; P < .001).
Results showed an association of KRAS variant status with superior OS compared with KRAS wild-type status among patients treated with immunotherapy alone (median OS, 21.1 months vs. 13.6 months; P = .03). The association remained significant on an adjusted Cox model (HR = 0.77; 95% CI, 0.61-0.98).
“However, among patients treated with the immunotherapy and chemotherapy combination, KRAS status did not matter and was not associated with survival — median OS was approximately 20 months, regardless of KRAS status,” Aggarwal said.
Patients with KRAS wild-type status had shorter median OS after treatment with immunotherapy alone vs. combination therapy, but the difference did not reach statistical significance (13.6 months vs. 19.3 months; adjusted HR = 1.19; 95% CI, 0.89-1.58).
“Looking within groups defined by KRAS status, whereas patients with KRAS variant had similar survival with immunotherapy or combined with chemotherapy, patients with KRAS wild-type had numerically worse survival when treated with immunotherapy monotherapy,” Aggarwal said. “We wish to look at co-mutation status in future research, such as STK11 and KEAP, which may impact outcomes among patients treated with immunotherapy.”
For more information:
Charu Aggarwal, MD, MPH, can be reached at Division of Hematology/Oncology, University of Pennsylvania, 3400 Civic Center Blvd., South Pavilion, 10-137, Philadelphia, PA 19104; email: charu.aggarwal@pennmedicine.upenn.edu.
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