Pembrolizumab increases response in resectable gastric, gastroesophageal junction cancers
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Key takeaways:
- The addition of pembrolizumab improved pathologic complete response rate.
- The pembrolizumab regimen did not improve EFS or OS.
MADRID — Pembrolizumab with chemotherapy before and after surgery increased pathologic complete response among patients with locally advanced gastric or gastroesophageal junction cancer, according to findings presented at ESMO Congress.
However, the approach did not confer a statistically significant benefit in EFS or OS, results of the randomized phase 3 KEYNOTE-585 study showed.
“Additional studies are needed to elucidate the effectiveness of immune checkpoint inhibitors in this setting,” Kohei Shitara, MD, chief of the department of gastrointestinal oncology at National Cancer Center Hospital East in Japan, said during a presentation.
Recurrence is common among patients who undergo surgical resection with curative intent for localized gastric or gastroesophageal junction adenocarcinoma.
“Perioperative chemotherapy has improved outcomes in patients with localized gastric or gastroesophageal junction cancer,” Shitara said. “PD-1/PD-L1 inhibitor therapies in combination with chemotherapy have provided survival benefits in [the first-line setting] and promising antitumor activity in the perioperative setting. The overall benefit of combination neoadjuvant and adjuvant chemotherapy and immune checkpoint inhibition in patients with locally advanced, resectable [disease is unknown.”
Pembrolizumab (Keytruda, Merck) is an anti-PD-1 therapy.
In KEYNOTE-585, treatment-naive patients received neoadjuvant chemotherapy with pembrolizumab or placebo, followed by adjuvant chemotherapy with pembrolizumab or placebo, followed by single-agent pembrolizumab or placebo.
The study included 1,007 patients. The main cohort included 804 patients assigned 1:1 to pembrolizumab (n = 402) or placebo (n = 402). A separate safety cohort included 203 patients assigned pembrolizumab (n = 100) or placebo (n = 103).
In the main cohort, chemotherapy consisted of cisplatin plus either capecitabine or 5-FU. In the safety cohort, chemotherapy consisted of 5-FU, docetaxel, oxaliplatin and leucovorin (FLOT).
Pathologic complete response rate by blinded independent central review, OS in the main cohort and safety in the FLOT cohort served as primary endpoints.
At ESMO, Shitara presented results from a prespecified third interim analysis.
Median follow-up was 47.7 months in the main cohort and 46.3 months in the FLOT cohort.
Results from the main cohort showed a statistically significant improvement in pathologic complete response rate with pembrolizumab (12.9% vs. 2%; P < .0001). This benefit persisted in a combined analysis of the main and FLOT cohorts (13% vs. 2.4%; P < .0001).
Researchers observed a numerical improvement in median EFS with pembrolizumab, but the difference did not meet statistical significance (main cohort, 44.4 months vs. 25.3 months; HR = 0.81; 95% CI, 0.67-0.99; main and FLOT cohorts, 45.8 months vs. 25.7 months; HR = 0.81; 95% CI, 0.68-0.97).
The difference in median OS between the pembrolizumab and placebo groups also did not reach statistical significance (main cohort, 60.7 months vs. 58 months; HR = 0.9; 95% CI, 0.73-1.12; main and FLOT cohorts, 60.7 months vs. not reached; HR = 0.93; 0.76-1.12).
At 36 months, a slightly higher percentage of patients in the pembrolizumab group remained alive at 24 months (main cohort, 72% vs. 69%; main and FLOT cohorts, 72% vs. 70%) and at 36 months (main cohort, 65% vs. 60%; main and FLOT cohorts, 65% vs. 61%).
A comparable percentage of patients assigned pembrolizumab vs. placebo experienced grade 3 or higher drug-related adverse events (64% vs. 63%). Four patients (1%) in the pembrolizumab group and two (< 1) in the placebo group experienced grade 5 treatment-related adverse events.
Treatment-related adverse events led to treatment discontinuation for 23% of those in the pembrolizumab group and 20% in the placebo group.
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Shitara K, et al. Abstract LBA74. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
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