Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC
Alexandria TM Lee,1 Misako Nagasaka1– 3 1University of California Irvine School of Medicine, Department of Medicine, Orange, CA, 92868, USA; 2Chao Family Comprehensive Cancer Center, Orange, CA, 92868, USA; 3St. Marianna University School of Medicine, Department of Medicine, Kawasaki, JapanCorrespon...
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Dove Medical Press
2024-12-01
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| Series: | Lung Cancer: Targets and Therapy |
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| Online Access: | https://www.dovepress.com/adagrasib-in-krystal-12has-not-broken-the-kras-g12c-enigma-code-of-the-peer-reviewed-fulltext-article-LCTT |
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| author | Lee AT Nagasaka M |
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| description | Alexandria TM Lee,1 Misako Nagasaka1– 3 1University of California Irvine School of Medicine, Department of Medicine, Orange, CA, 92868, USA; 2Chao Family Comprehensive Cancer Center, Orange, CA, 92868, USA; 3St. Marianna University School of Medicine, Department of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, Department of Medicine, Division of Hematology/Oncology, UC Irvine, Orange, CA, 92602, USA, Email nagasakm@hs.uci.eduAbstract: Mutations in KRAS G12C are among the more common oncogenic driver mutations in non-small cell lung cancer (NSCLC). In December 2022, the US Food and Drug Administration (FDA) granted accelerated approval to adagrasib, a small molecule covalent inhibitor of KRAS G12C, for the treatment of patients with locally advanced or metastatic KRAS G12C mutant NSCLC who received at least one prior systemic therapy based on promising results from phase 1 and 2 trials wherein adagrasib demonstrated a median PFS of 6.5 months. Results from the phase 3 KRYSTAL-12 trial were recently presented, showing benefit with adagrasib compared to docetaxel, with participants in the adagrasib group demonstrating a PFS of 5.5 months compared to 3.8 months in the docetaxel group. However, these results fall short of the 6-month PFS benchmark that had seemed achievable from what had been seen in phase 1 and 2 trials, mirroring similarly disappointing results from the CodeBreaK 200 trial wherein sotorasib, the first-in-class KRAS G12C inhibitor, also failed to meet the 6-month benchmark also thought to be possible when examining earlier trials. These results raise the question of adagrasib’s true value in the second-line treatment setting and compel us to explore more potent novel therapies, combination therapies, and more as we seek to break the 6-month PFS barrier in the treatment of KRAS G12C mutant NSCLC.Keywords: Kirsten rat sarcoma viral oncogene homolog gene, docetaxel, sotorasib |
| format | Article |
| id | doaj-art-c0949fc777584d62a16acd00e469abe2 |
| institution | Kabale University |
| issn | 1179-2728 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Lung Cancer: Targets and Therapy |
| spelling | doaj-art-c0949fc777584d62a16acd00e469abe22024-12-17T17:00:25ZengDove Medical PressLung Cancer: Targets and Therapy1179-27282024-12-01Volume 1516917698459Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLCLee ATNagasaka MAlexandria TM Lee,1 Misako Nagasaka1– 3 1University of California Irvine School of Medicine, Department of Medicine, Orange, CA, 92868, USA; 2Chao Family Comprehensive Cancer Center, Orange, CA, 92868, USA; 3St. Marianna University School of Medicine, Department of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, Department of Medicine, Division of Hematology/Oncology, UC Irvine, Orange, CA, 92602, USA, Email nagasakm@hs.uci.eduAbstract: Mutations in KRAS G12C are among the more common oncogenic driver mutations in non-small cell lung cancer (NSCLC). In December 2022, the US Food and Drug Administration (FDA) granted accelerated approval to adagrasib, a small molecule covalent inhibitor of KRAS G12C, for the treatment of patients with locally advanced or metastatic KRAS G12C mutant NSCLC who received at least one prior systemic therapy based on promising results from phase 1 and 2 trials wherein adagrasib demonstrated a median PFS of 6.5 months. Results from the phase 3 KRYSTAL-12 trial were recently presented, showing benefit with adagrasib compared to docetaxel, with participants in the adagrasib group demonstrating a PFS of 5.5 months compared to 3.8 months in the docetaxel group. However, these results fall short of the 6-month PFS benchmark that had seemed achievable from what had been seen in phase 1 and 2 trials, mirroring similarly disappointing results from the CodeBreaK 200 trial wherein sotorasib, the first-in-class KRAS G12C inhibitor, also failed to meet the 6-month benchmark also thought to be possible when examining earlier trials. These results raise the question of adagrasib’s true value in the second-line treatment setting and compel us to explore more potent novel therapies, combination therapies, and more as we seek to break the 6-month PFS barrier in the treatment of KRAS G12C mutant NSCLC.Keywords: Kirsten rat sarcoma viral oncogene homolog gene, docetaxel, sotorasibhttps://www.dovepress.com/adagrasib-in-krystal-12has-not-broken-the-kras-g12c-enigma-code-of-the-peer-reviewed-fulltext-article-LCTTkirsten rat sarcoma viral oncogene homolog genedocetaxelsotorasib |
| spellingShingle | Lee AT Nagasaka M Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC Lung Cancer: Targets and Therapy kirsten rat sarcoma viral oncogene homolog gene docetaxel sotorasib |
| title | Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC |
| title_full | Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC |
| title_fullStr | Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC |
| title_full_unstemmed | Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC |
| title_short | Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC |
| title_sort | adagrasib in krystal 12 nbsp has not broken the kras g12c enigma code of the unspoken 6 month pfs barrier in nsclc |
| topic | kirsten rat sarcoma viral oncogene homolog gene docetaxel sotorasib |
| url | https://www.dovepress.com/adagrasib-in-krystal-12has-not-broken-the-kras-g12c-enigma-code-of-the-peer-reviewed-fulltext-article-LCTT |
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