Researchers Release Chemo-Immunotherapy Treatment Outcomes Results in Patients with KRAS-Mutant NSCLC Subtypes

Approximately 235,000 individuals in the United States are diagnosed each year with lung cancer.¹ Non–small-cell lung cancer (NSCLC) accounts for approximately 84% of these lung cancer cases. If diagnosed in the early stages, NSCLC survival rates after surgical resection are relatively high, but the majority of cases are diagnosed at advanced stages when there is only a 1-year survival rate of 10%.² Lung adenocarcinoma, the most common type of lung cancer, represents 40% of all lung cancers.³ It is the most common subtype diagnosed in nonsmokers and evolves from the mucosal glands in the lungs.³

Cytotoxic chemotherapy has historically been the only treatment choice for patients with NSCLC, but targeted therapy against gene mutations has been introduced in recent years.⁴ Targeted therapy has been found to be more effective than chemotherapy and has less toxicity.⁴ One target for mutation is the Kirsten rat sarcoma (KRAS) mutation, an oncogenic driver in advanced NSCLC.⁴ The KRAS mutation predominantly occurs in lung adenocarcinoma and is a RAS/MAPK signaling cascade mediator that leads to unregulated cell growth and disease progression.⁵ There is great diversity among the KRAS-mutant subtypes, with KRAS^G12C being the most common subtype.⁴ These mutations occur in up to 30% of global NSCLC cases and are associated with poor patient outcomes.^4,6

A study was recently released at the virtual 2021 American Society of Clinical Oncology annual meeting on the chemo-immunotherapy outcomes of patients with the KRAS^G12C mutation compared with other molecular KRAS-mutant NSCLC subtypes. The investigators identified 137 patients with advanced/metastatic KRAS-mutant lung cancers treated with chemo-immunotherapy regimens as first-line therapy.⁶ These patients were divided into KRAS^G12C mutation and non-G12C mutation groups. Progression-free survival (PFS) and overall survival (OS) were calculated and compared between the groups.⁶ KRAS^G12C mutations occurred in 62 patients (45%) while 55% harbored non-G12C mutations.⁶ In 40% of the patients with KRAS^G12C mutation, a concurrent STK11 mutation was identified, and KEAP1 mutations were found in 32% of the patients.⁶

The median OS was 21 months for KRAS^G12C and 14 months for patients with non-KRAS^G12C mutations.⁶ Overall, the chemo-immunotherapy response rate for patients with KRAS^G12C was 40% and 31% in non-KRAS^G12C subtypes.⁶ PFS was 7.3 months for KRAS^G12C and 6.1 months for non-KRAS^G12C subtypes.⁶ Co-mutations with STK11 and/or KEAP1 in patients with KRAS^G12C had an association with shorter PFS (15.8 months vs 5.1 months).⁶

This study demonstrated that chemo-immunotherapy treatment outcomes are similar between KRAS^G12C mutations and patients with non-KRAS^G12C subtypes and poor with concurrent STK11 and/or KEAP1 mutations.

References

1. American Cancer Society. Key Statistics for Lung Cancer. Revised January 12, 2021. www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed June 26, 2021.
2. Román M, Baraibar I, López I, et al. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target. Mol Cancer. 2018;17:33.
3. Myers DJ, Wallen JM. Lung adenocarcinoma. National Center for Biotechnology Information StatPearls. Updated March 24, 2021. www.ncbi.nlm.nih.gov/books/NBK519578. Accessed July 12, 2021.
4. Lei L, Wang WX, Yu ZY, et al. A real-world study in advanced non-small cell lung cancer with KRAS mutations. Transl Oncol. 2020;13:329-335.
5. Ferrer I, Zugazagoitia J, Herbertz S, et al. KRAS-mutant non-small cell lung cancer: from biology to therapy. Lung Cancer. 2018;124:53-64.
6. Arbour KC, Ricciuti B, Rizvi H, et al. Chemo-immunotherapy outcomes of KRAS-G12C mutant lung cancer compared to other molecular subtypes of KRAS-mutant lung cancer. J Clin Oncol. 2021;39(suppl 15):9088.