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277 Combined neoadjuvant chemo-immunotherapy therapy achieves superior downstaging of resectable non-small cell lung cancer as compared to chemotherapy, mono or dual immunotherapy
  1. Boris Sepesi,
  2. Erin Corsini,
  3. Annikka Weissferdt,
  4. Apar Pataer,
  5. Mehmet Altan,
  6. Mara Antonoff,
  7. George Blumenschein,
  8. Yasir Elamin,
  9. Frank Fossella,
  10. Bonnie Glisson,
  11. Wayne Hofstetter,
  12. Jonathan Kurie,
  13. Xiuning Le,
  14. Cheuk Hong Leung,
  15. Heather Lin,
  16. Charles Lu,
  17. Reza Mehran,
  18. Frank Mott,
  19. David Rice,
  20. Jack Roth,
  21. Ferdinandos Skoulidis,
  22. Stephen Swisher,
  23. Anne Tsao,
  24. Ara Vaporciyan,
  25. Garret Walsh,
  26. Jianjun Zhang,
  27. Don Gibbons,
  28. John Heymach and
  29. Tina Cascone
  1. University of Texas MD Anderson Cancer Center, Houston, TX, USA


Background Tumor and nodal downstaging following neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC) are important markers of therapeutic response associated with favorable prognosis. We studied the impact of four different systemic neoadjuvant therapies on tumor, nodal and overall pathological downstaging of surgically resectable I-IIIA NSCLC (AJCC 7th edition).

Methods Our study cohorts consisted of NSCLC patients treated with three cycles of neoadjuvant platinum doublet chemotherapy from 2001–2012 (N=302, 84%), and patients treated on the NEOSTAR study (NCT03158129) who received neoadjuvant nivolumab (N=21,6%), nivolumab plus ipilimumab (N=16, 4%), or platinum doublet chemotherapy plus nivolumab (N=22, 6%). Clinical and pathological (yp) T and N staging were evaluated for downstaging and upstaging; differences were assessed using Fisher’s exact test.

Results Following neoadjuvant platinum doublet chemotherapy, nivolumab, nivolumab plus ipilimumab and platinum doublet chemotherapy plus nivolumab, the rates of clinical-to-pathological ypT downstaging were 26% (N=79), 29% (N=6), 38% (N=6) and 59% (N=13), respectively, p =0.012 (table 1). The rates of clinical-to-pathological ypN downstaging in patients with clinical N1 or N2 disease with each therapy were 55% (N=96), 50% (N=3), 50% (N=2), and 42% (N=5) respectively, p =0.862. Overall clinical-to-pathological (ypT and/or ypN) downstaging rates were 38% (N=114), 38% (N=8), 38% (N=6), and 68% (N=15) respectively, p=0.048. The proportions of patients being overall upstaged following each therapy were 28% (N=85), 38% (N=8), 38% (N=6) and 14% (N=3), respectively, p=0.251. These results suggest superior downstaging effect and clinically meaningful lower upstaging probability of combined platinum doublet chemotherapy plus nivolumab as compared to other neoadjuvant regimens.

Abstract 277 Table 1

Response to Chemotherapy, Immunotherapy, and Combination Therapy

Conclusions The combination of neoadjuvant platinum doublet chemotherapy with nivolumab achieves the most robust tumor and overall pathological downstaging and decreases the probability of upstaging at surgery. Whether the overall downstaging effect results in improved survival will be determined with longer follow-up, in conjunction with results from ongoing phase III neoadjuvant chemo-immunotherapy trials.

Trial Registration NCT03158129

Ethics Approval This study was approved by the University of Texas MD Anderson Institutional Review Board with a waiver of informed consent, protocol 2020-0337.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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