Nahomi Tokudome

Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab

OBJECTIVES Patients treated with nivolumab often experience its unique adverse events, called immune-related adverse events (irAEs). Regarding the mechanisms of immune-checkpoint inhibitors (ICIs), the occurrence of irAEs may also reflect antitumor responses. Here, we report the clinical correlation between irAEs and efficacy in NSCLC patients treated with nivolumab. MATERIALS AND METHODS Between December 2015 and February 2017, 38 advanced NSCLC patients were treated in our institution. All the patients were enrolled in our single-institutional, prospective, observational cohort study (UMIN000024414). IrAEs were defined as having a potential immunological basis that required more frequent monitoring and potential intervention. We divided the patients into two groups (irAEs group or no-irAEs group) and evaluated the objective response rate (ORR) and progression-free survival (PFS). RESULTS The median age of the patients was 68.5 years (range 49-86 years); male/female ratio was 28/10; squamous/non-squamous cell carcinoma cases were 10/28; performance status was 0-1/2/3, 7/26/5. Among the overall population, ORR was 23.7% and median PFS was 91days. At the data cutoff, 14 irAEs were observed. The most common irAE was interstitial pneumonia (n=5). Other irAEs were hypothyroidism (n=4), hyperthyroidism, hypopituitarism, liver dysfunction, rash, and elevated thyroid stimulating hormone levels (n=1, each). Patients with irAEs had significantly higher ORRs compared with no-irAE patients (63.6% versus 7.4%, p <0.01). Similarly, the PFS among irAE patients was longer (median: not reached [95% confidence interval {CI}: 91days to not applicable]) than no-irAE patients (median 49days [95% CI: 36-127days], hazard ratio [HR] 0.10 [95% CI: 0.02-0.37, p<0.001]). Landmark analysis of patients who achieved PFS ≥60days demonstrated similar tendencies, but this was not significant (HR 0.28 [95% CI: 0.04-1.46], p=0.13). CONCLUSION There was a correlation between irAE and efficacy in NSCLC patients treated with nivolumab.

Development of predictive liquid biomarkers for response to treatment in small cell lung cancer

Small cell lung cancer (SCLC), despite being initially chemosensitive, behaves aggressively and tends to progress rapidly after or during first-line chemotherapy. Predictive indicators of response to specific treatment for SCLC have not yet been established. Carter et al . had reported that they established a genetic classifier to predict whether SCLCs were “chemosensitive (sensitive relapse)” or “chemorefractory (refractory relapse)”. They used whole genome amplification products of native circulating tumor cell (CTC) from patients to develop this classifier. These CTC classifiers could accurately identify patients with SCLC as “sensitive relapse” or “refractory relapse” to first-line chemotherapy. Although this study represented a remarkable step forward in biomarker research in SCLC, classifiers obtained in the same fashion at disease progression could not predict the response to further treatment. This may imply that the inherent genetic background for the initial response to first-line chemotherapy differs from that for newly acquired resistance to treatment. In order to improve our understanding of the biological backgrounds of SCLC, extensive research into concepts such as cancer stem cells, epithelial mesenchymal transition/ mesenchymal epithelial transition, and circulating tumor microemboli might be necessary.

Applicability of the Japanese equation for estimating glomerular filtration rate in patients with advanced-stage thoracic cancer

BACKGROUND The 24-h creatinine clearance (24-h Ccr) and the Cockcroft-Gault equation (CG) are commonly used as markers of renal function in clinical practice. However, the utility of the Japanese equation for estimating glomerular filtration rate (eGFR) in cancer patients has not yet been evaluated. The aim of this cross-sectional study was to investigate the extent and correlating factors for differences between eGFR and both 24-h Ccr and CG in advanced-stage thoracic cancer patients. METHODS eGFR, 24-h Ccr, and CG were calculated in 90 patients with thoracic malignancies. We evaluated how these three parameters are affected by clinical factors, including age, body surface area, serum creatinine concentration, and body mass index. RESULTS eGFR and CG were significantly correlated with 24-h Ccr (r=0.64, p<0.001 and; r=0.67, p<0.001, respectively). However, the median value derived from eGFR was higher than the median 24-h Ccr and the CG value (74.0, 65.2, and 63.9mL/min, respectively). Age had a significant positive correlation with the differences between eGFR and both 24-h Ccr and CG value (r=0.30, p=0.005 and; r=0.47, p<0.001, respectively). The differences between eGFR and the other two parameters were significantly higher in older patients (age≥70 years) than in younger patients (age<70 years) (p=0.023, p<0.001, respectively). CONCLUSIONS eGFR is likely to overestimate the renal function of elderly cancer patients. A modified equation for evaluating the renal function of Japanese older patients might be needed.