Treatment with the next-generation ALK-receptor tyrosine kinase inhibitor (TKI), iruplinalkib, reduced the risk of disease progression or death by 66% when compared with Xalkori (crizotinib) as a first-line treatment for patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC), according to findings from the phase 3 INSPIRE trial recently published in the Journal of Thoracic Oncology.
“Results from this INSPIRE study provide evidence for potential global clinical studies of iruplinalkib,” researchers noted in the study, stating that iruplinalkib demonstrated both improved progression-free survival (PFS; the time a patient lives without their disease spreading or worsening) and intracranial antitumor activity (the prevention of tumors growing or spreading within the brain) versus Xalkori.
“Iruplinalkib may be a new treatment option for patients with advanced ALK-positive and ALK TKI-naïve NSCLC,” researchers wrote.
Following iruplimalkib’s approval in China for treating ALK-positive, Xalkori-resistant or -intolerant advanced NSCLC, data from INSPIRE were presented at the 2023 World Conference on Lung Cancer by study co-author Dr. Runxiang Yang of Yunnan Cancer Hospital in Kunming, China, prompting Dr. Rami Manochakian — associate professor of medicine; program director, hematology/oncology fellowship; and vice chair of education in the division of hematology/oncology at Mayo Clinic Florida — to note in The ASCO Post that “iruplinalkib may join (Alecensa [alectinib]), (Lorbrena [lorlatinib]) and (Alunbrig [brigatinib] as a first-line treatment option for advanced ALK-positive NSCLC.”
INSPIRE, according to a news release from iruplinalkib developer Qilu Pharmaceutical, is a randomized phase 3 clinical trial being held at 40 centers in China and led by Professor Shi Yuanaki of the Cancer Hospital of Chinese Academy of Medical Services, and between Sept. 4, 2019 and Dec. 2, 2020 the trial enrolled 292 patients who had received diagnoses of locally advanced or metastatic ALK-positive NSCLC. The INSPIRE participant population included 81 patients who had central nervous system (CNS) metastases.
Researchers reported in the study that the median progression-free survival for the iruplinalkib-treated cohort, at 27.7 months, was “significantly longer” than that experienced by the Xalkori at 14.6 months. The median overall survival (OS; the time a patient lives following treatment, regardless of disease status) had not been reached at a median follow-up time of 26.7 months in the iruplinalkib cohort and 25.9 months in the Xalkori group, meaning more than half of the participating patients in both arms were still alive.
Iruplinalkib was additionally found to lead to a median duration of tumor response of 26.8 months, versus 12.9 months via Xalkori. Among patients with CNS metastases at baseline the iruplinalkib had an intracranial (within the head) objective response rate (ORR: patients whose disease responded partially or completely to disease) of 57.9%, compared to 25.6% for patients treated with Xalkori, while the intracranial complete response rates were 31.6% and 2.6%, respectively.
Median treatment duration was 23.9 months for patients treated with iruplinalkib and 12.9 months for those treated with Xalkori, with researchers reporting that grade 3 or 4 side effect frequency was 51.7% and 49.7%, respectively.
The most common grade 3 or 4 side effects among patients treated with iruplinalkib were hypertension and abnormal liver function (9.1% each), and among the Xalkori cohort were decreased absolute neutrophil count (a type of white blood cell, 14.1%), with serious treatment-related side effects occurring in 14% of iruplinalkib patients and 10.7% of Xalkori patients.
Treatment discontinuation due to death occurred for four patients in the iruplinalkib arm and three patients in the Xalkori arm, with researchers stating that none of the deaths in the iruplinalkib group were found to be related to iruplinalkib, while two of the deaths in the control group were found to be related to Xalkori.
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