Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer

Author(s): Mariano Provencio, M.D., Ph.D., Ernest Nadal, M.D., Ph.D., José L. González-Larriba, M.D., Ph.D., Alex Martínez-Martí, M.D., Reyes Bernabé, M.D., Joaquim Bosch-Barrera, M.D., Joaquín Casal-Rubio, M.D., Virginia Calvo, M.D., Ph.D., Amelia Insa, M.D., Santiago Ponce, M.D., Ph.D., Noemí Reguart, M.D., Ph.D., Javier de Castro, M.D., Ph.D., Joaquín Mosquera, M.D., Ph.D., Manuel Cobo, M.D., Ph.D., Andrés Aguilar, M.D., Guillermo López Vivanco, M.D., Carlos Camps, M.D., Ph.D., Rafael López-Castro, M.D., Teresa Morán, M.D., Isidoro Barneto, M.D., Delvys Rodríguez-Abreu, M.D., Ph.D., Roberto Serna-Blasco, M.Sc., Raquel Benítez, Ph.D., Carlos Aguado de la Rosa, M.D., Ramón Palmero, M.D., Florentino Hernando-Trancho, M.D., Ph.D., Javier Martín-López, M.D., Alberto Cruz-Bermúdez, Ph.D., Bartomeu Massuti, M.D., and Atocha Romero, Pharm.D., Ph.D.
Source: N Engl J Med 2023; 389:504-513 DOI: 10.1056/NEJMoa2215530
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Neoadjuvant chemotherapy trial with post op nivolumab for 6 months shows promising results.


Approximately 20% of patients with non–small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients.


In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety.


A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P=0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan–Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan–Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%).


In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II number, NCT03838159. opens in new tab; EudraCT number, 2018-004515-45. opens in new tab.)

Author Affiliations

From Hospital Universitario Puerta de Hierro–Majadahonda (M.P., V.C., R.S.-B., J.M.-L., A.C.-B., A.R.), Hospital Universitario Clínico San Carlos (J.L.G.-L., C.A.R., F.H.-T.), Hospital Universitario 12 de Octubre (S.P.), Hospital Universitario La Paz (J.C.), and the Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (R. Benítez), Madrid, Institut Català d’Oncologia, L’Hospitalet de Llobregat (E.N., R.P.), Vall d’Hebron Institute of Oncology, Hospital Universitari Vall d’Hebrón (A.M.-M.), the Medical Oncology Department Hospital Clinic and Translational Genomics and Targeted Therapies in Solid Tumors, Institut de Investigacions Biomèdiques (N.R.), and Instituto Oncológico Dr. Rosell, Dexeus University Hospital (A.A.), Barcelona, Hospital Universitario Virgen del Rocio, Seville (R. Bernabé), Institut Català d’Oncologia, Hospital Universitari Dr. Josep Trueta, Girona (J.B.-B.), Complejo Hospitalario Universitario de Vigo, Pontevedra (J.C.-R.), Fundación Instituto de Investigación Sanitaria, Hospital Clínico Universitario de Valencia (A.I.), and Hospital General Universitario de Valencia, Universidad de Valencia and Centro de Investigación Biomédica en Red Cáncer (C.C.), Valencia, Complejo Hospitalario Universitario A Coruña, A Coruña (J.M.), the Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, Instituto de Investigación Biomédica de Málaga, Málaga (M.C.), Hospital Universitario Cruces, Barakaldo (G.L.V.), Hospital Clínico Universitario de Valladolid, Valladolid (R.L.-C.), the Medical Oncology Department, Catalan Institute of Oncology, Badalona–Germans Trias i Pujol Hospital, Badalona Applied Research Group in Oncology, Fundació Institut de Investigado de Ciences de la Salut Germans Trias i Pujol, Department of Medicine, Universitat Autònoma de Barcelona, Campus Can Ruti, Badalona (T.M.), Hospital Universitario Reina Sofia, Córdoba (I.B.), Complejo Hospitalario Universitario Insular–Materno Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), and Hospital Universitario Dr. Balmis Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante (B.M.) — all in Spain.

Leave a Comment

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

Related Articles

Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non–Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial

Preliminary results of DESTINY-Lung02 show strong efficacy with trastuzumab deruxtecan (T-DXd). Overall response rate (ORR) was about 50%, with duration of response of 16.8 months. This is now FDA-approved and is an available therapy for patients with ERBB2 mutations after 1st line platinum-based chemo +/- immunotherapy. This is preferred over traditional trastuzumab or afatinib. Interestingly, some responses were seen in the ERBB2-negative patients who had over-expression by IHC. Please continue to sequence your patients and enroll in targeted therapy trials.

Read More »

Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC

Osimertinib with chemotherapy improved the chance of being alive at two years compared to targeted therapy alone at 57 vs 41%. Further analysis of FLAURA2 and new studies will surely look to identify which patients benefit most from the combination of targeted therapy and chemotherapy. For young or healthy patients, this is an acceptable first line option. This is not yet reflected on NCCN but is likely to be added soon.

Read More »

Perioperative Durvalumab for Resectable Non–Small-Cell Lung Cancer

Adding Durvalumab to chemotherapy preop improved CR (17.2 vs4.3%) regardless of PLD -1 status. We already have approval for neoadjuvant chemotherapy and immunotherapy combinations in resectable lung cancer, so not sure if this regimen will be favored.
The unique thinkg about this one is that durva was also given post op ( not in the opidvo trial) but you can give pembrolizumab as adjuvant in those pts who had opdivo preop, and now pembrolizumab just got its approval in the neoadjuvant setting (last month) in which nit is given post op too.

Read More »

Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05)

A nicely done Spanish study showing that in metastatic NSCLC, asymptomatic patients with brain metastases can have radiation therapy deferred.
Starting with systemic therapy was found to be reasonable and effective, validating a common practice. Patients were treated with atezolizumab + carboplatin + pemetrexed + steroids, and any number of brain mets was allowed as long as they had at least one 10mm in size or greater. This study excluded patients harboring EGFR/ALK driver mutations.

Read More »