Race Does Not Correlate With High Renal Toxicity With Pemetrexed/Pembrolizumab in NS-NSCLC

Treatment with platinum-based pemetrexed combined with pembrolizumab (Keytruda) in patients with nonsquamous non–small cell lung cancer (NSCLC) resulted in acute kidney injury (AKI) and death in more Black American patients compared with White American patients, according to a retrospective analysis from the phase 3 KEYNOTE-189 clinical trial (NCT02578680).

The study, which was recently presented during the ESMO Annual Congress, analyzed 134 patients with advanced nonsquamous NSCLC who identified as either non-Hispanic Black or non-Hispanic White. The population had a median age of 66.5 years and was largely made of males (48.5%). Twenty-four percent of the patients were Black, and the remainder (75.4%) were White.

Results showed AKI development in 8.1% of patients who were evaluated, with a 4.5-month median tome to development. The investigators of the study did not identify any significant difference in AKI development between patients who identified as Black and those who identified as White. Other suspected risk factors of renal toxicity like hypertension (P =.67), diabetes mellitus (P =.37), cardiovascular disease (P =.68), or chronic kidney disease (P =.33).

In terms of mortality, the median survival of the overall patient population was 15.2 months (95% CI, 12.7-22.2) at a median follow-up of 24.5 months.

In an interview with Targeted Oncology™, Nino Balanchivadze, MD, FACP, senior administrative fellow of the Hematology and Oncology Fellowship Program at Henry Ford Cancer Institute, discussed the toxicity profile of platinum pemetrexed with pembrolizumab in patients with nonsquamous NSCLC treated in the KEYNOTE-189 study and how clinical characteristics may impact treatment.

TARGETED ONCOLOGY™: Can you discuss the toxicity profile of platinum pemetrexed in combination with pembrolizumab as observed in the KEYNOTE-189 study?

Balanchivadze: As we know in the KEYNOTE-189 study, acute kidney injury was observed in about 5.2% of the patients in the pembrolizumab combination group compared with only 0.5% in the placebo combination group. A total of 4.2% of the patients treated with pembrolizumab and carboplatin/pemetrexed and revealed all grade increased blood creatine, of which 0.7% were grade 3 to 4, and renal adverse events in the pembrolizumab combination group led to treatment discontinuation in about 2% of the patients. It’s also important to note that most of the patient in the trial received chemotherapy with care carboplatin, as the platinum compound was only given to about 25%.

What was the rationale for specifically looking at toxicity based on race in this population?

Prior studies have shown that compared to White Americans, Black Americans are at higher risk of morbidity and mortality associated with chronic kidney diseases. Black patients are at a 3 to 4 times higher risk of developing kidney failure compared to White patients, irrespective of cancer. Data regarding renal impairment with platinum pemetrexed and pembrolizumab treatment in Black patients is lacking. So, the main driver for our study is to investigate if there is there was more renal toxicity observed in Black Americans compared to white Americans that were treated with a company coming up to therapy.

What methods were used to conduct this study?

As part of the study, we analyzed medical records of self-identified Black and White patients with advanced nonsquamous non–small cell lung cancer, who are treated with the platinum pemetrexed and pembrolizumab between January 1, 2017, and November 12, 2021. At Henry Ford Health System in Detroit, Michigan, we have recorded serum creatine and calculated promoter filtration rate before the first cycle, the combination treatment and over the duration of the therapy as well as prior to death if that was applicable. We defined acute kidney injury as an increase in serum creatinine 1.5 times that baseline value, and the reduction in glomerular filtration rate of greater than 30% was considered significant.

What were the findings that you presented during the ESMO Annual Meeting?

So, we found we had a total of 134 patients that were included in the analysis. The mean age of patients was 66.5 years, and about 48.5% patients were men. A total of 33 patients, or 24% percent of our patients were non-Hispanic Black, and 75.4 patients were non-Hispanic White, there were 10 patients who develop acute kidney injury and with the meaning in time to the development of injury, or 0.5 months of black or white race with acute kidney injury. And the odds of developing acute kidney injury was not increased in patients with a history of hypertension, diabetes mellitus, cardiovascular disease or chronic kidney disease. We also found that a total of 17 or 13.4% of patients had significantly reduced glomerular filtration rates, and patients that had history of chronic kidney disease were more likely to have reduced glomerular filtration rate.

_Reference:

_{Balanchivadze N, Nasser Z, Shahid M, et al. Renal toxicity in black patients with non-squamous non-small cell lung cancer treated with combination platinum-pemetrexed-pembrolizumab therapy. Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract 317P.}