Prognostic Implication of KRAS G12C Mutation in a Real-World KRAS-Mutated Stage IV NSCLC Cohort Treated With Immunotherapy in The Netherlands.

Introduction: With the approval of G12C inhibitors as the second line of treatment for KRAS G12C-mutated NSCLC, and the expanding research regarding targeting KRAS, it is key to understand the prognostic implication of KRAS G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV KRAS G12C-mutated NSCLC to those with a KRAS non-G12C mutation in a first-line setting of (chemo)immunotherapy. Methods: This nationwide population-based study used real-world data from The Netherlands Cancer Registry. We selected patients with stage IV KRAS-mutated lung adenocarcinoma diagnosed in 2019 to 2020 who received first-line (chemo-)immunotherapy. Primary outcome was OS. Results: From 28,120 registered patients with lung cancer, 1185 were selected with a KRAS mutation, of which 494 had a KRAS G12C mutation. Median OS was 15.5 months (95% confidence interval [CI]: 13.6-18.4) for KRAS G12C versus 14.0 months (95% CI:11.2-15.7) for KRAS non-G12C (p = 0.67). In multivariable analysis, KRAS subtype was not associated with OS (hazard ratio = 0.95, 95% CI: 0.82-1.10). For the subgroup with programmed death-ligand 1 at 0% to 49% who received chemoimmunotherapy, median OS was 13.3 months (95% CI: 10.5-15.2) for G12C and 9.8 months (95% CI: 8.6-11.3) for non-G12C (p = 0.48). For the subgroup with programmed death-ligand 1 more than or equal to 50% who received monoimmunotherapy, the median OS was 22.0 months (95% CI: 18.4-27.3) for G12C and 18.9 months (95% CI: 14.9-25.2) for non-G12C (p = 0.36). Conclusions: There was no influence of KRAS subtype (G12C versus non-G12C) on OS in patients with KRAS-mutated stage IV NSCLC treated with first-line (chemo)immunotherapy.

Survival of patients with KRAS G12C mutated stage IV non-small cell lung cancer with and without brain metastases treated with immune checkpoint inhibitors.

INTRODUCTION: Few data is available on whether brain metastases (BM) influence survival in patients with stage IV KRAS G12C mutated (KRAS G12C+ ) non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitor (ICI) +/- chemotherapy ([chemo]-ICI). METHODS: Data was retrospectively collected from the population-based Netherlands Cancer Registry. The cumulative incidence of intracranial progression, overall survival (OS) and progression free survival (PFS) was determined for patients with KRAS G12C+ stage IV NSCLC diagnosed January 1 - June 30, 2019, treated with first-line (chemo)-ICI. OS and PFS were estimated using Kaplan-Meier methods and BM+ and BM- groups were compared using log-rank tests. RESULTS: Of 2489 patients with stage IV NSCLC, 153 patients had KRAS G12C+ and received first-line (chemo)-ICI. Of those patients, 35% (54/153) underwent brain imaging (CT and/or MRI), of which 85% (46/54) MRI. Half of the patients with brain imaging (56%; 30/54) had BM, concerning one-fifth (20%; 30/153) of all patients, of which 67% was symptomatic. Compared to BM-, patients with BM+ were younger and had more organs affected with metastasis. Around one-third (30%) of patients with BM+ had ≥5 BM at diagnosis. Three quarters of patients with BM+ received cranial radiotherapy prior to start of (chemo)-ICI. The 1-year cumulative incidence of intracranial progression was 33% for patients with known baseline BM and 7% for those without (p = 0.0001). Median PFS was 6.6 (95% CI 3.0-15.9) and 6.7 (95% CI 5.1-8.5) months for BM+ and BM- (p = 0.80), respectively. Median OS was 15.7 (95% CI 6.2-27.3) and 17.8 (95% CI 13.4-22.0) months for BM+ and BM- (p = 0.77), respectively. CONCLUSION: Baseline BM are common in patients with metastatic KRAS G12C+ NSCLC. During (chemo)-ICI treatment, intracranial progression was more frequent in patients with known baseline BM, justifying regular imaging during treatment. In our study, presence of known baseline BM did not influence OS or PFS.

Ethnicity and rectal cancer management in New Zealand.

AIM: Research shows survival disparities between Maori and non-Maori colon cancer patients, with comorbidity and cancer care being major contributing factors. We studied rectal cancer management and survival in a cohort of Maori and non-Maori patients with a newly diagnosed rectal cancer. METHODS: 194 Maori and non-Maori patients diagnosed with rectal cancer between 2006 and 2008 were identified from the New Zealand Cancer Registry. Medical records were reviewed and patients compared on presentation, patient and tumour characteristics, and receipt and timing of treatment. Cox regression models were fitted to compare cancer-specific survival. RESULTS: Compared to non-Maori patients, Maori patients were younger (mean age at diagnosis 63.5 and 69.2 for Maori and Non-Maori respectively; p<0.001) and had higher prevalence of comorbidity. Stage, grade and tumour size distributions were similar. Almost all stage I-III patients (97%) underwent definitive surgery, with no difference between Maori and non-Maori. Maori patients waited longer for referral to medical oncologists (40 days vs. 33 days; p=0.03). Results suggested Maori patients with stage IV disease may be less likely than non-Maori to be referred to palliative care (13% vs. 40%; p=0.07). The hazard ratio for cancer-specific death for Maori compared with non-Maori patients was 1.24 (95% CI 0.65-2.35). CONCLUSION: The findings suggest both similarities and some differences in treatment and outcomes between Maori and non-Maori rectal cancer patients, but firm conclusions are limited by small sample size.