Study Suggests Need for New Second-Line NSCLC Therapies to Follow Osimertinib

A study published in Oncology Therapy¹ found that the duration of the line of treatment (LOT) following first-line osimertinib, a tyrosine kinase inhibitor (TKI), for epidermal growth factor receptor (EGFR) mutation–positive metastatic non–small cell lung cancer (mNSCLC) was short and tolerability was low. This emphasizes the need for new second-line therapies that address EGFR TKI resistance in NSCLC.

As of 2024, the leading cause of mortality related to cancer in the United States is lung cancer.² NSCLC is the most common subtype of lung cancer in the country, including adenocarcinoma and squamous cell carcinoma. EGFR TKIs are recommended for the treatment of EGFR-mutated mNSCLC, with the third-generation TKI osimertinib being the preferred option. However, even with its safety and efficacy, the majority of patients develop resistance and are subsequently treated with systemic chemotherapy. Characterizing the line of therapy after osimertinib discontinuation was the focus of this study.

Subsequent line of therapies were not found to be tolerated in patients with NSCLC | Image credit: appledesign - stock.adobe.com

The researchers used medical and pharmacy claims from IQVIA PharMetrics Plus to perform a retrospective analysis. The database included information from up to 150 million people in the United States, and patients were included if they were aged 18 years or older and had at least 1 medical claim that indicated a diagnosis of lung cancer from January 2010 to September 2019. Patients also needed at least 1 medical claim of a secondary malignancy and at least 1 pharmacy claim for an EGFR TKI after the diagnosis date of mNSCLC. Patients needed to have taken osimertinib and a LOT afterward between November 2015 and September 2019. Patients were excluded if they had prior medical claims for cancer in the 6 months before their diagnosis of mNSCLC.

LOTs were determined using an algorithm based on literature published previously. Any medication filled or administrated within 14 days of a previous medication was defined as combination regimen. LOTs were categorized into EGFR TKI monotherapy, EGFR TKI combination, platinum-based chemotherapy, immunotherapy, and other therapies.

There were 135 patients included in the study who had a median (IQR) age of 59 (52-64) years and were primarily female (64.4%). The mean (SD) time from diagnosis to a second LOT (index) was 22.5 (14.9) months, and the mean number of LOTs before the index treatment was 2.2 (1.1).

Platinum-based chemotherapy was the most common index LOT at 57.0%, with 40.3% in combination with immunotherapy. A total of 15.6% of patients had EGFR TKI monotherapy, and immunotherapy alone was used in 13.3% of patients. Retreatment with EGFR TKI either alone or in combination with another therapy was done in 23.7% of patients, with 12.6% using osimertinib. The mean duration of index LOT was 3.0 (4.1) months, and mean duration of platinum-based therapy with immunotherapy was 2.7 (3.0) months.

The longest time to discontinuation (TTD) was seen in patients who received EGFR TKI monotherapy in the second line (median, 4.6 months; 95% CI, 1.9-5.1). The shortest TTD was seen in patients who used immunotherapy alone (median, 1.5 months; 95% CI, 0.5-2.8). Similar TTDs were found in patients who used platinum-based chemotherapy with immunotherapy (median, 2.1 months; 0.7-3.1) and patients who used other treatments (median, 2.0 months; 95% CI, 0.03-not estimable).

A total of 31.9% of patients had at least 1 hospitalization during the index LOT. The mean inpatient admission rates were high in patients treated with platinum-based chemotherapy and immunotherapy (19.4 [37.9] per 100 patient-months) and in patients using only immunotherapy (15.6 [31.4] per 100 patient-months) vs EGFR TKI monotherapy (7.1 (13.9) per 100 patient-months). A total of 35.6% of patients had at least 1 ED visit, and the overall mean all-cause admission rate was 15.9 (32.3) per 100 patient-months. The rate of ED visits was more than 60% higher in the immunotherapy alone treatment group compared with the platinum chemotherapy and immunotherapy groups. The mean number of hospitalizations related to adverse events was 20.7 per 100 patient-months.

There were some limitations to this study. Detailed clinical information is not recorded in all claims data, and claims data can be subject to inaccuracies in coding. Reasons for discontinuation of treatment were also not available. Rates of adverse events could have been underestimated due to data only being available for hospital admissions. The study also included a small sample size.

The researchers concluded that the effectiveness of the LOT following osimertinib was limited due to the short duration seen in the included data. Tolerability issues were present when patients used platinum-based chemotherapies with immunotherapy, which led to hospitalizations or visits to the emergency department.

"These data underscore the high unmet need for new therapeutic options to address EGFR TKI resistance in this patient population," the authors concluded.

References

1. Marrett E, Kwong WJ, Song J, Manceur A, Sendhill S, Wu E. Treatment patterns and resource use after osimertinib discontinuation in patients with EGFR + metastatic NSCLC. Oncol Ther. Published online July 30, 2024. doi:10.1007/s40487-024-00292-5
2. Cancer stat facts: common cancer sites. National Cancer Institute. 2024. Accessed August 5, 2024. https://seer.cancer.gov/statfacts/html/common.html