Adagrasib, a KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1–1b part of the KRYSTAL-1 phase 1–2 study.
Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non–Small-Cell Lung Cancer (NADIM phase II trial)￼
Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non–small-cell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: NCT03081689). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported.
This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analysis were secondary objectives of the trial.
OS at 36 months was 81.9% (95% CI, 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI, 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR], 0.20; 95% CI, 0.06 to 0.63, and HR, 0.07; 95% CI, 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR, 0.26; 95% CI, 0.07 to 0.93, and HR, 0.04; 95% CI, 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72).
The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival.
Author Affiliations1Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain;2Institut Català d’Oncologia, L’Hospitalet De Llobregat, Barcelona, Spain;3Fundación INCLIVA, Hospital Clínico Universitario de Valencia, Valencia, Spain;4Hospital Universitario A Coruña, A Coruña, Spain;5Hospital Universitario de Vigo, Pontevedra, Spain;6Hospital Universitario Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain;7Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;8Hospital Insular de Gran Canaria, Las Palmas, Spain;9Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Barcelona, Spain;10Hospital Universitario La Paz, Madrid, Spain;11Hospital Universitario Regional de Malaga, Spain;12Hospital Universitario Cruces, Barakaldo, Spain.;13Hospital Universitario de Salamanca, Salamanca, Spain;14Hospital Universitario Virgen del Rocio, Seville, Spain;15Hospital Clínic, Barcelona, Spain;16Hospital Universitario Reina Sofia, Córdoba, Spain;17Instituto Oncológico Dr Rosell. Hospital Universitario Quiron Dexeus, Grupo QuironSalud, Barcelona, Spain;18Spanish Lung Cancer Group, Barcelona, Spain;19Centro de Investigación Principe Felipe, Valencia, Spain;20Atrys Health, Barcelona, Spain;21Hospital General de Alicante, Alicante, Spain
First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1)
Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRASG12C. We report results from a phase I/IB study of adagrasib in non–small-cell lung cancer, colorectal cancer, and other solid tumors harboring the KRASG12C mutation.
Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I-IIIA Completely Resected Non–Small-Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update
ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer
The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer and no disease progression after concurrent chemoradiotherapy.