Association between pathologic response and survival after neoadjuvant therapy in lung cancer

Julie Stein Deutsch, Ashley Cimino-Mathews, Elizabeth Thompson, Mariano Provencio, Patrick M. Forde, Jonathan Spicer, Nicolas Girard, Daphne Wang, Robert A. Anders, Edward Gabrielson, Peter Illei, Jaroslaw Jedrych, Ludmila Danilova, Joel Sunshine, Keith M. Kerr, Mia Tran, Judith Bushong, Junliang Cai, Vipul Devas, Jaclyn NeelyDavid Balli, Tricia R. Cottrell, Alex S. Baras, Janis M. Taube

Research output: Contribution to journalArticlepeer-review


Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (0% residual viable tumor (RVT) in primary tumor (PT) and lymph nodes (LNs)), and is approved for treatment of resectable lung cancer. Pathologic response assessment after neoadjuvant therapy is the potential analog to radiographic response for advanced disease. However, %RVT thresholds beyond pathologic complete response and major pathologic response (≤10% RVT) have not been explored. Pathologic response was prospectively assessed in the randomized, phase 3 CheckMate 816 trial (NCT02998528), which evaluated neoadjuvant nivolumab (anti-programmed death protein 1) plus chemotherapy in patients with resectable lung cancer. RVT, regression and necrosis were quantified (0–100%) in PT and LNs using a pan-tumor scoring system and tested for association with EFS in a prespecified exploratory analysis. Regardless of LN involvement, EFS improved with 0% versus >0% RVT-PT (hazard ratio = 0.18). RVT-PT predicted EFS for nivolumab plus chemotherapy (area under the curve = 0.74); 2-year EFS rates were 90%, 60%, 57% and 39% for patients with 0–5%, >5–30%, >30–80% and >80% RVT, respectively. Each 1% RVT associated with a 0.017 hazard ratio increase for EFS. Combining pathologic response from PT and LNs helped differentiate outcomes. When compared with radiographic response and circulating tumor DNA clearance, %RVT best approximated EFS. These findings support pathologic response as an emerging survival surrogate. Further assessment of the full spectrum of %RVT in lung cancer and other tumor types is warranted. registration: NCT02998528 .

Original languageEnglish (US)
Pages (from-to)218-228
Number of pages11
JournalNature medicine
Issue number1
StatePublished - Jan 2024

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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