EFS Relies on Residual Tumor in NSCLC

SAN DIEGO — The diploma of event-free survival (EFS) after surgical procedure in early-stage non–small cell lung most cancers (NSCLC) depends upon the quantity of residual tumor, in accordance with a put up hoc evaluation of the KEYNOTE-671 research.

The authors additionally discovered that perioperative pembrolizumab (Keytruda, Merck) continued to point out a profit over placebo of their new outcomes, which David R. Jones, MD, offered on the World Conference on Lung Cancer (WCLC) 2024 on September 8.

The new analysis steered that the diploma of residual viable tumor (RVT) after neoadjuvant remedy is “related to poorer EFS time, regardless of remedy arm,” mentioned Jones, chief, Thoracic Service, Division of Surgical procedure, Memorial Sloan Kettering Most cancers Middle, New York Metropolis. He underlined that the outcomes do point out the “clinically important EFS advantages” of pembrolizumab on this inhabitants “prolong to sufferers with residual viable tumors,” with the drug related to “larger pathologic regression” than placebo.

“This helps the advantage of a perioperative routine of neoadjuvant pembrolizumab plus chemotherapy and adjuvant pembrolizumab for early-stage NSCLC,” he mentioned.

Earlier results of KEYNOTE-671 confirmed that in contrast with placebo, using pembrolizumab each earlier than and following surgical procedure in sufferers with resectable stage II, IIIA, or IIIB NSCLC was related to a 42% discount within the danger for development, recurrence, or dying. These have been revealed final 12 months, previous to the US Food and Drug Administration (FDA) approving pembrolizumab with platinum-containing chemotherapy as neoadjuvant remedy and with the continuation of single-agent pembrolizumab because the postsurgical adjuvant remedy for resectable NSCLC.

An exploratory evaluation steered there was an EFS profit with pembrolizumab vs placebo in sufferers who skilled a pathologic full or main pathologic response, however there was a necessity to check the connection in a extra granular method.

Jones and colleagues due to this fact performed a put up hoc evaluation of KEYNOTE-671 to find out the affiliation between EFS and the diploma of pathologic regression after resection, outlined as %RVT.

Submit Hoc Evaluation Strategies and Outcomes

Jones reminded the viewers that the research included 797 people with stage II, IIIA, or IIIB NSCLC with N2 stage illness, who had undergone no prior remedy and have been capable of endure surgical procedure.

The contributors have been randomized to as much as 4 cycles of neoadjuvant pembrolizumab or placebo alongside cisplatin-based chemotherapy. Surgical procedure was carried out inside 20 weeks of the primary neoadjuvant dose (or 4-8 weeks after the final dose if lower than 4 cycles got). Then, 4-12 weeks after surgical procedure, sufferers have been continued with pembrolizumab or placebo for as much as 13 cycles.

The median follow-up was 36.6 months, and the present evaluation included 320 sufferers from the pembrolizumab arm who had pathologically evaluable tumors, alongside 300 from the placebo arm.

Jones defined that each the teams have been “effectively matched, particularly for intercourse, tumor histology, tumor stage, and tumor PD-L1 [programmed death ligand 1] standing.”

He reported that following neoadjuvant remedy, the median %RVT within the pembrolizumab arm was 29.5% vs 52.0% within the placebo arm. Particularly, 17.5% pembrolizumab sufferers had a %RVT > 60% vs 35.0% of these within the placebo arm.

The crew discovered that the period of EFS in pembrolizumab sufferers was related to post-resection %RVT.

Amongst these with a %RVT of 0% to ≤ 5%, 24-month EFS was 90.8%, which fell to 74.7% in these with a %RVT > 5% to ≤ 30%, 62.1% in sufferers with a %RVT > 30% to ≤ 60%, and 40.2% amongst these with a %RVT > 60%.

Related findings have been seen within the placebo group, at 24-month EFS charges of 83.3%, 62.5%, 46.2%, and 34.8%, respectively, and when inspecting EFS at 36 months.

Jones famous that whereas RVT was indicative of EFS, “additional research are wanted to validate %RVT for analysis of outcomes on this affected person inhabitants.”

KEYNOTE-671 vs CheckMate 816

Tina Cascone, MD, PhD, Division of Thoracic/Head and Neck Medical Oncology, The College of Texas MD Anderson Most cancers Middle, Houston, commented that there’s an “unmet want” in early-stage NSCLC.

She famous that 3-year EFS/disease-free charges with neoadjuvant, perioperative, and adjuvant immunotherapy/chemotherapy approaches in stage II-III NSCLC are roughly 53%-65%.

“Simpler customized remedies and biomarkers are wanted to enhance upon these benchmarks,” emphasised Cascone, who was not concerned within the research.

Cascone highlighted that the present outcomes present the EFS good thing about perioperative pembrolizumab extends to sufferers with RVT after the neoadjuvant part, however solely as much as a cutoff of 60percentRVT.

She pointed to knowledge from CheckMate 816, which additionally regarded on the relationship between pathologic regression and EFS with neoadjuvant nivolumab (Opdivo, Bristol Myers Squibb) however didn’t embody lymph nodes within the evaluation.

It isn’t clear, Cascone mentioned, whether or not pathologic regression following neoadjuvant immunotherapy in lymph nodes might differ from that within the tumor and have an effect on the survival profit.

An additional query, she famous, stays as to the contribution of the adjuvant part of remedy to the EFS final result and whether or not that pertains to %RVT.

The research was funded by Merck Sharp & Dohme LLC. Jones declared relationships with Merck, AstraZeneca, Genentech, Extra Well being, and DAVA Oncology. Cascone declared relationships with AstraZeneca, Bristol Myers Squibb, Genentech, Merck, oNKo-innate, Pfizer, RAPT Therapeutics, Regeneron, Dava Oncology, European Society for Medical Oncology IDEOlogy Well being, Worldwide Affiliation for the Research of Lung Most cancers, OncLive, Parker Institute for Most cancers Immunotherapy, Physicians’ Schooling Useful resource, Society for Immunotherapy of Most cancers, ASCO Submit, Bio Ascend, Scientific Care Choices, Mark Basis for Most cancers Analysis, The Medical Educator Consortium, Medscape Medical Information, PEAK Medical, and PeerView.