Ian Chau, MD
The invited discussant for the ATTRACTION-3 study was Ian Chau, MD, Consultant Medical Oncologist at The Royal Marsden Hospital, London and Surrey, United Kingdom. Dr. Chau first congratulated the investigators for successfully conducting a randomized phase III trial in metastatic esophageal cancer of squamous cell histology. An online search for such trials in this disease entity turned up zero hits, indicating a paucity of evidence to guide the treatment of this disease, he said.
The best evidence he could find, he said, was a Cochrane review of four small randomized phase II studies in the first-line setting, in which the hazard ratio for survival was 0.76, favoring chemotherapy.1 There appear to be no phase III randomized second-line trials with which to compare the results of ATTRACTION-3 and to show the results are “plausible and reproducible,” he said.
But there are the results of KEYNOTE-181, which evaluated pembrolizumab vs chemotherapy as second-line treatment in patients with both squamous cell carcinoma and adenocarcinoma.2 Though pembrolizumab was “directionally favored,” the primary endpoint narrowly missed statistical significance. Among patients with high programmed cell death ligand 1 (PD-L1) expression, a significant survival benefit was shown with pembrolizumab (hazard ratio = 0.69; P = .0074), leading to its approval by the U.S. Food and Drug Administration in this subset.
In the evaluation of pembrolizumab’s benefit in squamous cell carcinoma, a subgroup analysis in KEYNOTE-181 revealed very similar outcomes to those of ATTRACTION-3: a hazard ratio of 0.78 (P = .0095) and “almost identical” 12-month and 18-month survival rates, Dr. Chau noted.
Given the data from both ATTRACTION-3 and KEYNOTE-181, he said, it can be concluded “that PD-1 [programmed cell death protein 1] inhibitors work in squamous cell carcinoma of the esophagus in the second-line setting,” probably in non-Asian patients as well as Asians, he said. Regarding the importance of PD-L1 expression and the optimal cut points, “we still need more data,” he added.
Considering the improved survival, safety profile, and quality of life over chemotherapy seen now with nivolumab, he said, the treatment paradigm of this disease has shifted. For inoperable or metastatic recurrent squamous cell carcinoma, first-line treatment remains platinum/fluoropyrimidine-based chemotherapy, but after disease progression, treatment should be with nivolumab or, for patients with a PD-L1 composite score ≥ 10, pembrolizumab (in accordance with its label). Later lines of treatment should consist of chemotherapy.
Data for these drugs in the first-line setting will come from CheckMate 648 and KEYNOTE-590, which are recruiting or underway. ■
DISCLOSURE: Dr. Chau has served on the advisory boards for Eli Lilly, Bristol-Myers Squibb, MSD, Bayer, Roche, Merck-Serono, Five Prime Therapeutics, AstraZeneca, Oncologie International, and Pierre Fabre.
REFERENCES
1. Janmaat VT, Steyerberg EW, van der Gaast A, et al: Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer. Cochrane Database Syst Rev 11:CD004063, 2017.
