Advertisement

Expert Point of View: Samuel J. Klempner, MD


Advertisement
Get Permission

Samuel J. Klempner, MD, Associate Professor at Massachusetts General Hospital and Harvard Medical School, commented on the NEONIPIGA study for The ASCO Post.

“This study was the first prospective data set to show what many have suspected—that neoadjuvant immune checkpoint blockade would lead to a high pathologic response rate in microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) gastroesophageal adenocarcinomas. The rate of TRG (tumor regression grading) 1 or 2 was 72.4%, which is encouraging in a population where the expected pathologic complete response rate is between 5% and 16% with chemotherapy.1,2 

Samuel J. Klempner, MD

Samuel J. Klempner, MD

“Although follow-up remains limited, the reported event-free survival looks to be very favorable. Importantly, these data parallel the equally impressive report for neoadjuvant dostarlimab in dMMR stage II to III rectal cancers, where the clinical complete response rate was 100% in a phase II trial.3

“A prior meta-analysis suggesting a lack of benefit to perioperative or adjuvant chemotherapy in patients with MSI-H/dMMR disease is compelling, and now we have data from NEONIPIGA supporting the actionability of MSI/MMR status in this patient population.4 In my opinion, the NEONIPIGA trial underscores the need to identify this patient population by testing all our patients with localized gastroesophageal adenocarcinoma for MSI/MMR status.

Dr. Klempner continued: “The NEONIPIGA trial raises several important questions in patients with MSI-H/dMMR locoregional disease. First, do we need dual checkpoint blockade, or would a PD-1 blocker alone achieve similar outcomes? Second, are there patients who could forgo a planned surgery and instead undergo close surveillance? Third, could we further risk-stratify this population with emerging tools such as circulating tumor DNA? Longer follow-up and planned correlative analysis from the NEONIPIGA trial coupled with the ongoing phase II INFINITY trial [ClinicalTrials.gov identifier NCT04817826] will be important additions to this exciting area of gastroesophageal cancer research.” 

DISCLOSURE: Dr. Klempner has served as a consultant or advisor to Astellas, Daiichi  Sankyo, Merck, Bristol Myers Squibb, Eli Lilly, Sanofi-Aventis, Natera, and AstraZeneca; and owns stock in Turning Point Therapeutics.

REFERENCES

1. Smyth EC, Fassan M, Cunningham D, et al: Effect of pathologic tumor response and nodal status on survival in the medical research council adjuvant gastric infusional chemotherapy trial. J Clin Oncol 34:2721-2727, 2016.

2. Al-Batran SE, Hofheinz RD, Pauligk C, et al: Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): Results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 17:1697-1708, 2016.

3. Lumish MA, Cohen JL, Stadler ZF, et al: PD-1 blockade alone for mismatch repair deficient locally advanced rectal cancer. 2022 ASCO Gastrointestinal Cancers Symposium. Abstract 16. Presented January 20, 2022.

4. Pietrantonio F, Miceli R, Raimondi A, et al: Individual patient data meta-analysis of the value of microsatellite instability as a biomarker in gastric cancer. J Clin Oncol 37:3392-3400, 2019.

 


Related Articles

Neoadjuvant Checkpoint Inhibitor Doublet Yields Complete Responses in Gastroesophageal Cancers

In patients with resectable microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) gastric and gastroesophageal junction adenocarcinoma, dual checkpoint inhibition with ipilimumab and nivolumab given as neoadjuvant therapy led to a pathologic complete response rate of 58.6%,...

Advertisement

Advertisement



Advertisement