The efficacy of osimertinib does not significantly vary according to the body size variables of patients with T790M-positive non–small cell lung cancer who progress on prior EGFR tyrosine kinase inhibitors, according to findings from a new study published in <em>Thoracic Cancer</em>.<br />
The efficacy of osimertinib does not significantly vary according to the body size variables of patients with T790M-positive nonsmall cell lung cancer (NSCLC) who progress on prior EGFR tyrosine kinase inhibitors (TKIs), according to findings from a new study published inThoracic Cancer.
“While osimertinib treatment is recognized as the standard-of-care for patients harboring the T790Mresistance mutation who progress on first-line EGFR-TKIs, the standard dose of osimertinib is 80 mg/day, a uniform dosage regardless of patients’ body size,” wrote the authors, led by Taihei Ono, MD, Kitasato University School of Medicine, Sagamihara-City, Japan. “The results of this prospective observational study show that body surface area (BSA) and body mass index (BMI) have no statistically significant effect on the clinical outcomes of osimertinib monotherapy, including the response rate and progression-free survival (PFS), in patients with T790M-positive advanced NSCLC who experience disease progression after first-line EGFR-TKI therapy.”
The authors conducted a prospective observational cohort study at Kitasato University Hospital to evaluate the efficacy and safety of osimertinib. They selected patients who had experienced disease progression after first-line EGFR-TKI therapy including gefitinib, erlotinib (Tarceva), and afatinib. The group was mostly female (66%) with a median age of 73, and two-thirds (66%) had an ECOG performance status (PS) of 0 or 1.
The authors included in the final analysis 47 NSCLC patients treated with osimertinib during a 2-year period. All had adenocarcinoma and stage IV disease or postoperative recurrence. Their median BSA was 1.50 m2(range, 1.161.79 m2), while their median BMI was 21.5 kg/m2(range, 14.028.2 kg/m2).
Compared with the low BSA group, the high BSA group (BSA ≥1.5 m2) contained significantly more men (87% vs. 35%,P< 0.001) and patients younger than 75 (72% vs. 44%,P< 0.001). The same was true of smokers (79% vs. 42%,P= 0.024), patients with good PS (62% vs. 34%,P= 0.03), and patients with L858R point mutation (66% vs. 29%,P= 0.015).
The high BMI group (BMI ≥21.5 kg/m2) included significantly higher percentages of patients with a good performance status (62% vs. 27%,P= 0.01) and L858R point mutations (61% vs. 29%,P= 0.048)
With 27 of the 47 patients displaying an objective response, the objective response rate (ORR) was 57.4% (95% CI, 43.3%71.5%). The authors used the median BSA and BMI values as the cutoff to evaluate the impact of body size on the efficacy of osimertinib monotherapy. The response rate was 59.1% (95% CI, 38.6%–79.6%) in the low BSA group and 56% (95% CI, 36.5%–75.5%) in the high BSA group, indicating no statistically significant difference (P= 0.83).
Likewise, there was no statistically significant difference between the BMI groups (P= 0.64). The response rate was 60.8% (95% CI, 40.880.8%) in the low BMI group and 54.1% (95% CI, 34.2–74.0%) in the high BMI group.
With a median follow-up of 10.6 months, the median PFS of the entire patient population was 7.6 months (95% CI, 6.48.8). The median OS was 14.7 months (95% CI, 9.1–20.5).
In examining the PFS data when stratified by BSA and BMI, the authors found that the differences were statistically nonsignificant. The median PFS in the low BSA group was 9.1 months (95% CI, 3.714.5), while the high BSA group had PFS of 7.6 months (95% CI, 6.7–8.5;P= 0.69). With BMI, the median PFS in the low BMI group was 7.6 months (95% CI, 2.013.2). PFS in the high BMI group was 7.6 months (95% CI, 6.6–8.6;P= 0.38).
Likewise, there were no significant differences in the toxicity frequencies relative to either BSA or BMI. Diarrhea was the most common non-hematologic toxicity of any grade (18 patients, 38.3%), followed by skin rash (15 patients, 31.9%), and fatigue (10 patients, 21.3%). Grade 3 diarrhea occurred in 2 patients.
Thrombocytopenia was the most common hematologic toxicity of any grade, affecting 10 patients (21.3%). This was followed by anemia (7 patients, 14.9%) and leukopenia (6 patients, 12.8%). Grade 3 thrombocytopenia was observed in 1 patient.
Using univariate analysis, the authors identified PS, brain metastasis status, and the number of prior regimens as significantly predictive of PFS. Multivariate analysis identified patient age, PS, and EGFR genotype as independent predictors of PFS.
The authors also analyzed responses to osimertinib among patients with the T790M mutation. With a daily dose of 80 mg, the ORR was 83%. However, ORR decreased as the dose increased: 79% at 160 mg daily and 77% at 240 mg daily. “Thus, it is reasonable to conclude that the tumor responses of osimertinib therapy were not dose-dependent, and the observations of our study appear to support the lack of a correlation between tumor response and osimertinib dose,” Ono et al wrote.
The authors noted an important limitation in their study: the sample size may have been insufficient. Additionally, they noted that there was no pharmacokinetic validation accompanying the observations on the efficacy of osimertinib in relation to BSA and BMI.
As a next step, Ono et al propose future research examining the relationship between body size variables and the efficacy of osimertinib monotherapy in the first-line setting for NSCLC patients with sensitiveEGFRmutations.
Ono T, Igawa S, Ozawa T, et al. Evaluation of osimertinib efficacy according to body surface area and body mass index in patients with non-small cell lung cancer harboring an EGFR mutation: A prospective observational study.Thoracic Cancer.doi: 10.1111/1759-7714.13018