Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non–Small-Cell Lung Cancer (NADIM phase II trial)

Author(s): Mariano Provencio, MD, PhD1;Roberto Serna-Blasco, MSc1;Ernest Nadal, MD2;Amelia Insa, MD3;M. Rosario García-Campelo, MD4;Joaquín Casal Rubio, MD5;Manuel Dómine, MD6;Margarita Majem, MD7;Delvys Rodríguez-Abreu, MD8;Alex Martínez-Martí, MD9;Javier De Castro Carpeño, MD10;Manuel Cobo, MD11;Guillermo López Vivanco, MD12;Edel Del Barco, MD13;Reyes Bernabé Caro, MD14;Nuria Viñolas, MD15;Isidoro Barneto Aranda, MD16;Santiago Viteri, MD17;Eva Pereira, MSc18;Ana Royuela, PhD1;Virginia Calvo, MD1;Javier Martín-López, MD1;Francisco García-García, PhD19;Marta Casarrubios, MSc1;Fernando Franco, MD1;Estela Sánchez-Herrero, MSc1,20;Bartomeu Massuti, MD21;Alberto Cruz-Bermúdez, PhD1;and Atocha Romero, PhD1
Source: DOI: 10.1200/JCO.21.02660
Original Article
Professional photo of Lucio Gordan, MD
Another study showing that ctDNA will absolutely change how we manage and follow patients in a myriad of neoplasms, with decreased utilization of CT scans in the next decade.

PURPOSE

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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 Affiliations

1Hospital 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

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Daraxonrasib for Previously Treated RAS-Mutant Non–Small-Cell Lung Cancer

This feels like the first real crack in the "undruggable" non-G12C RAS wall in lung cancer: a pan-RAS(ON) inhibitor with responses across G12D, G12V, and other alleles in patients who had already received platinum and immunotherapy. At the 160–220 mg range (the phase 3 dose is 200 mg), patients who hadn't yet received docetaxel had a 42% response rate, median progression-free survival (PFS) of 8 mos, and median overall survival (OS) of 16 mos, which looks well ahead of what we expect from docetaxel, though that's a cross-trial comparison. The catch is tolerability: about half had grade 3 or higher events, 9 in 10 got rash, and most got diarrhea, so rash prophylaxis and proactive GI management will matter just as it does on PDAC. The randomized RASolve 301 trial against docetaxel is the one to watch before this moves into practice.

Read More »

SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1–High, Locally Advanced, Unresectable or Metastatic Non–Small Cell Lung Cancer

This is another nail in the anti-TIGIT coffin. In more than 500 patients with untreated PD-L1–high non–small cell lung cancer (NSCLC), adding tiragolumab to atezolizumab missed both primary endpoints, and the numerical progression-free survival (PFS) and overall survival (OS) gains never reached significance. What it did add was toxicity: twice the grade 3–4 adverse events (AEs) and more discontinuations. Together with the other failed TIGIT programs, this pretty much closes the door on chemo-free anti-TIGIT combinations in first-line NSCLC, so single-agent PD-(L)1 or chemo-IO stays the standard for these patients.

Read More »

First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations

Progression-free survival (PFS) was higher in the Sun group vs chemotherapy, 10.3 m vs 7.5 m with HR of .65 with higher responses (58.9% vs 31.1%) diarrhea high CK and anemia were the most common side effects. The issue is that amivan was not part of treatment and compared to chemotherapy ami in addition to chemotherapy had 11m PFS also in this trial few had brain mets so no evaluation for CNS protection or treatment. But an oral agent in patients who don’t want to come to the office often.

Read More »

Selpercatinib in Early-Stage RET Fusion–Positive Non–Small-Cell Lung Cancer

109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib and 61% with placebo (HR for disease recurrence, progression, or death, 0.17 P<0.001). Patients with stage IB, II, or IIIA non–small-cell lung cancer (NSCLC), event-free survival at 2 years was 94% with selpercatinib and 70% with placebo. Genomic testing is expanding now for early stage NSCLC. More study in the adjuvant setting showing promise with targeted therapy.

Read More »

Ensartinib in Resected ALK-Positive Non–Small-Cell Lung Cancer

It seems the old cliche of more drugs than patients is becoming true for most providers here. The data needs to mature further here but likely this will be another option for Anaplastic lymphoma kinase (ALK)+ non–small-cell lung cancer (NSCLC) patients in the adjuvant setting. It does look like CNS protection benefits are meaningful as well.

Read More »
Load More