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. 2023 Sep 11;41(9):1680-1688.e2.
doi: 10.1016/j.ccell.2023.08.004.

Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression

Brian G Topp  1 , Madhav Channavazzala  2 , Kapil Mayawala  3 , Dinesh P De Alwis  3 , Eric Rubin  3 , Alexandra Snyder  3 , Jedd D Wolchok  4 , Antoni Ribas  5
Affiliations

Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression

Brian G Topp et al. Cancer Cell. .

Abstract

While many patients are treated beyond progression (TBP), the magnitude and duration of clinical benefit in these patients have not been fully quantified. Data from 799 patients with melanoma (n = 176), non-small cell lung cancer (NSCLC; n = 146), gastric cancer (GC; n = 87), head and neck squamous cell carcinoma (HNSCC; n = 112), clear-cell renal cell carcinoma (ccRCC; n = 51), and urothelial carcinoma (UC; n = 227) TBP were included. Patients had received pembrolizumab beyond confirmed progressive disease (PD) per RECIST v1.1. A subset of patients displays a 30% reduction in the sum of lesion diameters in the post-progression period (melanoma 24.4%, NSCLC 11.6%, 12.6% GC, 8.9% HNSCC, 15.7% ccRCC, and 13.2% UC). Most patients show stable target lesion dynamics in the post-progression period (melanoma, 64.8%; NSCLC, 72.6%; GC, 69.0%, 75.9% HNSCC, 72.5% ccRCC, 75.3% UC). Pembrolizumab generates meaningful efficacy in a subset of patients treated beyond RECIST v1.1 progression.

Trial registration: ClinicalTrials.gov NCT01295827 NCT02335411 NCT02358031 NCT02853344 NCT02335424 NCT02853305.

Keywords: clear-cell renal cell carcinoma; gastric cancer; head and neck squamous cell carcinoma; melanoma; non-small cell lung cancer; pembrolizumab; postprogression response; urothelial carcinoma.

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Conflict of interest statement

Declaration of interests B.G.T. is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA. M.C. has nothing to disclose. K.M. is a stockholder of Merck & Co., Inc., Rahway, NJ, USA, and holds a leadership role (Vice President, Clinical Pharmacology, Clinical Development) at Generate Biomedicines. DPd.A. is a stockholder of Merck & Co., Inc., Rahway, NJ, USA, and holds a leadership role (Senior Vice President, Clinical Drug Development) at Generate Biomedicines. E.R. is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA; and holds a leadership role (Senior Vice President, Clinical Oncology) at Merck & Co., Inc., Rahway, NJ, USA. A.S. reports advisory/consultancy to Two River, Inc, holds a leadership role at Generate Biomedicines (CMO), and is an officer/on the board of directors for Navigating Cancer. J.D.W. reports a role of consultant for Adaptive Biotech, Amgen, Apricity, Ascentage Pharma, Astellas, AstraZeneca, Bayer, Beigene, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly and Company, F Star, Imvaq, Kyowa Hakko Kirin, Linneaus, MedImmune, Merck, Neon Therapeutics, Ono, Polaris Pharma, Polynoma, Psioxus, Puretech, Recepta, Takara Bio, Trieza, Truvax, Serametrix, Surface Oncology, Syndax, and Syntalogic; research support from AstraZeneca and Bristol Myers Squibb; and equity in Adaptive Biotechnologies; BeiGene; Imvaq; Linneaus; Potenza Therapeutics; Tizona Pharmaceuticals; and Trieza. A.R. reports leadership for PACT Pharma, Arcus Biosciences, and Lutris; stock and other ownership interests for Compugen, CytomX Therapeutics, Advaxis, Acrus Biosciences, Tango Therapeutics, PACT Pharma, Merus, ImaginAb, Lutris Pharma, Highlight, MapKure, 4c Biomked, Kite/Gilead, Isoplexis, Appia, Synthekine, Pluto, Inspirna, RAPT Therapeutics, and ImmPACT-Bio; honoraria from Merck Sharp & Dohme, Novartis, Amgen, Chugai/Roche, Genentech/Roche, Sanofi, Vedanta Biosciences, and AstraZeneca; a consulting or advisory role for Merck, Amgen, Novartis, Chugai Pharma, and Sanofi; research funding to institution from Agilent and Bristol Myers Squibb; and patents, royalties, other intellectual property for nonviral gene editing to Arsenal Bio.

Figures

Figure 1.
Figure 1.. Study design
ORR, objective response rate.
Figure 2.
Figure 2.
Waterfall and Swim Plots Best overall response and time on trial after progression for patients with (A and B) melanoma, (C and D) NSCLC, and (E and F) gastric cancer. NSCLC, non–small cell lung cancer.
Figure 3.
Figure 3.
Pre- and Post PD Tumor Dynamics Distribution of target lesion responses in preprogression and postprogression periods for patients with (A) melanoma, (B) NSCLC, and (C) gastric cancer. NSCLC, non-small cell lung cancer.
Figure 4.
Figure 4.
Post-PD Dynamics of New Metastatic Lesions Behavior of new metastatic lesions after initial appearance in patients with (A) melanoma and (B) NSCLC. New metastatic lesions for patients with gastric cancer in KEYNOTE-059 were recorded as present or absent but were not indexed (measured). NSCLC, non-small cell lung cancer; SLD, sum of longest diameter.
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