Long-term outcomes and molecular correlates of sotorasib efficacy in patients with pretreated KRAS G12C-mutated non-small-cell lung cancer: 2-Year analysis of CodeBreaK 100 Journal Article
| Authors: | Dy, G. K.; Govindan, R.; Velcheti, V.; Falchook, G. S.; Italiano, A.; Wolf, J.; Sacher, A. G.; Takahashi, T.; Ramalingam, S. S.; Dooms, C.; Kim, D. W.; Addeo, A.; Desai, J.; Schuler, M.; Tomasini, P.; Hong, D. S.; Lito, P.; Tran, Q.; Jones, S.; Anderson, A.; Hindoyan, A.; Snyder, W.; Skoulidis, F.; Li, B. T. |
| Article Title: | Long-term outcomes and molecular correlates of sotorasib efficacy in patients with pretreated KRAS G12C-mutated non-small-cell lung cancer: 2-Year analysis of CodeBreaK 100 |
| Abstract: | Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In the longest follow-up, to our knowledge, for a KRASG12C inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non-small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical trial (ClinicalTrials.gov identifier: NCT03600883). This multicenter, single-group, open-label phase I/phase II trial enrolled 174 patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC after progression on prior therapies. Patients (N = 174) received sotorasib 960 mg once daily with the primary end points for phase I of safety and tolerability and for phase II of objective response rate (ORR). Sotorasib produced an ORR of 41%, median duration of response of 12.3 months, progression-free survival (PFS) of 6.3 months, overall survival (OS) of 12.5 months, and 2-year OS rate of 33%. Long-term clinical benefit (PFS ≥ 12 months) was observed in 40 (23%) patients across PD-L1 expression levels, in a proportion of patients with somatic STK11 and/or KEAP1 alterations, and was associated with lower baseline circulating tumor DNA levels. Sotorasib was well tolerated, with few late-onset treatment-related toxicities, none of which led to treatment discontinuation. These results demonstrate the long-term benefit of sotorasib, including in subgroups with poor prognosis. © American Society of Clinical Oncology. |
| Keywords: | adult; cancer survival; controlled study; aged; major clinical study; overall survival; genetics; clinical trial; drug tolerability; advanced cancer; diarrhea; drug safety; side effect; cancer patient; progression free survival; liver toxicity; phase 2 clinical trial; carcinoma, non-small-cell lung; lung neoplasms; vasculotropin inhibitor; lung tumor; alanine aminotransferase; aspartate aminotransferase; multicenter study; patient safety; hemolytic anemia; platinum; open study; clinical effectiveness; biological therapy; k ras protein; protein p21; proto-oncogene proteins p21(ras); kras protein, human; programmed death 1 ligand 1; non small cell lung cancer; clinical outcome; protein kinase lkb1; overall response rate; transcription factor nrf2; kelch like ech associated protein 1; humans; human; male; female; article; alanine aminotransferase level; aspartate aminotransferase level; nf-e2-related factor 2; protein expression level; sotorasib; kelch-like ech-associated protein 1 |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 41 |
| Issue: | 18 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2023-06-20 |
| Start Page: | 3311 |
| End Page: | 3317 |
| Language: | English |
| DOI: | 10.1200/jco.22.02524 |
| PUBMED: | 37098232 |
| PROVIDER: | scopus |
| PMCID: | PMC10414711 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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