Skoulidis, Ferdinandos, Li, Bob T., Dy, Grace K., Price, Timothy J., Falchook, Gerald S., Wolf, Jurgen, Italiano, Antoine, Schuler, Martin, Borghaei, Hossein, Barlesi, Fabrice, Kato, Terufumi, Curioni-Fontecedro, Alessandra ORCID: 0000-0002-5778-5270, Sacher, Adrian ORCID: 0000-0001-7865-2701, Spira, Alexander, Ramalingam, Suresh S., Takahashi, Toshiaki, Besse, Benjamin, Anderson, Abraham, Ang, Agnes, Tran, Qui ORCID: 0000-0002-0760-964X, Mather, Omar, Henary, Haby, Ngarmchamnanrith, Gataree, Friberg, Gregory, Velcheti, Vamsidhar and Govindan, Ramaswamy (2021). Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N. Engl. J. Med., 384 (25). S. 2371 - 2382. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

BACKGROUND Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC). METHODS In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with KRAS p.G12C-mutated advanced NSCLC previously treated with standard therapies. The primary end point was objective response (complete or partial response) according to independent central review. Key secondary end points included duration of response, disease control (defined as complete response, partial response, or stable disease), progression-free survival, overall survival, and safety. Exploratory biomarkers were evaluated for their association with response to sotorasib therapy. RESULTS Among the 126 enrolled patients, the majority (81.0%) had previously received both platinum-based chemotherapy and inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). According to central review, 124 patients had measurable disease at baseline and were evaluated for response. An objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), including in 4 (3.2%) who had a complete response and in 42 (33.9%) who had a partial response. The median duration of response was 11.1 months (95% CI, 6.9 to could not be evaluated). Disease control occurred in 100 patients (80.6%; 95% CI, 72.6 to 87.2). The median progression-free survival was 6.8 months (95% CI, 5.1 to 8.2), and the median overall survival was 12.5 months (95% CI, 10.0 to could not be evaluated). Treatment-related adverse events occurred in 88 of 126 patients (69.8%), including grade 3 events in 25 patients (19.8%) and a grade 4 event in 1 (0.8%). Responses were observed in subgroups defined according to PD-L1 expression, tumor mutational burden, and co-occurring mutations in STK11, KEAP1, or TP53. CONCLUSIONS In this phase 2 trial, sotorasib therapy led to a durable clinical benefit without new safety signals in patients with previously treated KRAS p.G12C-mutated NSCLC.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Skoulidis, FerdinandosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, Bob T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dy, Grace K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Price, Timothy J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falchook, Gerald S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Italiano, AntoineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuler, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borghaei, HosseinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barlesi, FabriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kato, TerufumiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curioni-Fontecedro, AlessandraUNSPECIFIEDorcid.org/0000-0002-5778-5270UNSPECIFIED
Sacher, AdrianUNSPECIFIEDorcid.org/0000-0001-7865-2701UNSPECIFIED
Spira, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramalingam, Suresh S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takahashi, ToshiakiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Besse, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anderson, AbrahamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ang, AgnesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tran, QuiUNSPECIFIEDorcid.org/0000-0002-0760-964XUNSPECIFIED
Mather, OmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henary, HabyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ngarmchamnanrith, GatareeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friberg, GregoryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Velcheti, VamsidharUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Govindan, RamaswamyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-606576
DOI: 10.1056/NEJMoa2103695
Journal or Publication Title: N. Engl. J. Med.
Volume: 384
Number: 25
Page Range: S. 2371 - 2382
Date: 2021
Publisher: MASSACHUSETTS MEDICAL SOC
Place of Publication: WALTHAM
ISSN: 1533-4406
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COOCCURRING GENOMIC ALTERATIONS; RANDOMIZED PHASE-III; DOCETAXEL; INHIBITORS; NIVOLUMAB; TRIALMultiple languages
Medicine, General & InternalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60657

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