2026 Southeastern Residency Conference

Background
Non-small cell lung cancer (NSCLC) encompasses 87% of lung cancer cases with a 5-10% five-year survival rate1. For non-squamous NSCLC without sensitizing mutations, the KEYNOTE-189 trial showed the combination of carboplatin/pemetrexed plus pembrolizumab increased overall survival and progression-free survival over chemotherapy alone.  However, pembrolizumab and pemetrexed are both nephrotoxic agents. When studied using pembrolizumab plus pemetrexed/carboplatin vs. placebo plus pemetrexed/carboplatin, there was a 5.2% vs. 0.5% instance of acute kidney injury (AKI) that occurred2. This study was designed to evaluate the duration of response for patients on carboplatin/pemetrexed/pembrolizumab who developed versus did not develop an AKI

Methods:
This was a multicenter, retrospective cohort study of patients who underwent treatment with carboplatin/pemetrexed/pembrolizumab for non-squamous metastatic NSCLC. Data was collected from January 1, 2022 to December 31, 2025 from patients at Atrium Health Levine Cancer.. A report via electronic medical records in Epic was generated to select patients who have received carboplatin/pemetrexed/pembrolizumab. Within the AKI and no AKI groups, random selection occurred with data collection entered into a RedCAP database. Inclusion criteria consisted of  ≥18 years old, stage IV non-squamous NSCLC, and completion of at least 1 cycle of carboplatin/pemetrexed/pembrolizumab. Exclusion criteria were a creatinine clearance < 45 mL/min, a baseline use of prednisone or equivalent ≥ 10 mg not utilized for pre-medication and receiving any oncology treatment outside of Atrium Health facilities. The primary endpoint was the duration of response of first-line treatment after developing an AKI compared to patients who did not. Duration of response was defined by time to death or time to initiating second-line therapy. Secondary endpoints included total cycles of first-line therapy received, cycle of therapy AKI developed in, and re-initiation of treatment after AKI development. Demographics and baseline characteristics were analyzed using Fisher’s exact test (categorical values) and Wilcox rank sum test (continuous values). Time to initiation of second line therapy or death was analyzed with a Kaplan-Meier curve, reporting the log-rank test result between those with versus those without an AKI. Patients were censored at the maximum follow up time if no event was experienced.

Results
169 patients were screened with 80 patients included. The rate of AKI was 11%. Common baseline characteristics include 50-70 years old (59%), white (74%), with an average SCr <1.5 (96%). Eighty-three percent of  patients did not have a targetable mutation while 15% had KRAS G12C mutations and 2.5% had EBBR2 mutations. Tumor proportion score (TPS) <1% for the AKI group was 78% and 54% for the non-AKI group. Most deaths occurred in the non-AKI group (37/71 vs. 1/9, p=0.031), which failed to show a statistically significant difference in the two groups.

Conclusion
An early AKI during first-line non-small cell lung cancer treatment has been shown to reduce survival outcomes at 12 months4. This study aimed to evaluate the impact of an AKI could have on duration of response, which was found to have no statistically significant difference; however, the amount of people who had an AKI was larger than past literature studies2. Limitations that could have influenced the lack of statistical difference included not having enough patients to detect a statistically significant difference and different providers electing to use pembrolizumab and pemetrexed together versus pembrolizumab alone, influencing AKI occurrence.