FDA approvals in gastrointestinal cancers spark excitement in field
Click Here to Manage Email Alerts
FDA approvals of immunotherapies are among several exciting developments during the past couple of years in the field of upper gastrointestinal cancers, according to a speaker at Chemotherapy Foundation Symposium.
“These types of cancers are typically treated with chemoradiation followed by surgery. For the patients who have residual disease after surgery, there is still a chance for recurrence. Often these patients recur quickly —within the first couple of years — and distally, therefore making them incurable,” Sarbajit Mukherjee, MD, MS, assistant professor of oncology at Roswell Park Comprehensive Cancer Center, said during a presentation. “We have made the progress that we have made because patients have graciously participated in clinical trials. Please discuss clinical trials with your patients, as this is how we make progress together.”
In the global, phase 3, double-blind, randomized, placebo-controlled CheckMate 577 trial, the use of adjuvant nivolumab (Opdivo, Bristol Myers Squibb) significantly prolonged DFS among 794 adults with stage II to stage III resected esophageal and gastroesophageal junction cancer. Researchers observed a DFS benefit with nivolumab, a PD-1 inhibitor, across all prespecified subgroups, regardless of disease histology, pathologic lymph node status or tumor cell PD-L1 expression.
“CheckMate 577 tried to see if nivolumab would prevent recurrences, and based on these data, the FDA approved nivolumab as an adjuvant treatment for completely resected esophageal and gastroesophageal junction cancer after chemoradiation among patients with residual pathologic disease,” Mukherjee said.
There has been a lot of excitement in the HER2-positive population, as well.
Data from an interim analysis of the ongoing, randomized, placebo-controlled, multicenter KEYNOTE-811 trial showed the addition of pembrolizumab (Keytruda, Merck), an anti-PD-1 antibody, to the HER2-targeted antibody trastuzumab (Herceptin, Genentech) and chemotherapy resulted in a higher overall response rate (74% vs. 52%) among patients with HER2-positive metastatic gastric or gastroesophageal junction cancer. Median duration of response was 10.6 months (range, 1.1+ to 16.5+) with the pembrolizumab combination vs. 9.5 months (range, 1.4+ to 15.4+) with placebo.
“Based on these data, pembrolizumab received accelerated approval for this population of patients in May of this year,” Mukherjee said. “Almost every patient experienced disease control with the pembrolizumab combination and the duration of response was quite significant.”
Other approvals this year included use of nivolumab in combination with chemotherapy in the first-line setting for locally advanced, metastatic esophageal and gastroesophageal junction adenocarcinoma, regardless of PD-L1 status, and first-line pembrolizumab in combination with chemotherapy for locally advanced metastatic esophageal and gastroesophageal junction cancer, regardless of PD-L1 status or tumor histology, he added.
NCCN guidelines have also recommended cutoffs for PD-L1 combined positive score (CPS) for both nivolumab and pembrolizumab combinations.
The CheckMate 649 study showed nivolumab plus chemotherapy increased PFS and OS compared with chemotherapy alone among previously untreated patients with advanced gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma who had a PD-L1 CPS of 5 or greater.
“Based on these data, the FDA approved nivolumab for all-comers, regardless of PD-L1 CPS score,” Mukherjee said. “However, in patients with PD-L1 CPS less than 5, the benefit was not as much. Based on this, NCCN placed a category 1 recommendation for those with a PD-L1 CPS of 5 or greater.”
In the phase 3 KEYNOTE-590 study, researchers found the addition of pembrolizumab to chemotherapy improved OS, PFS and objective response rates among 749 patients with locally advanced/unresectable or metastatic adenocarcinoma or esophageal squamous cell carcinoma or Siewert type I esophagogastric junction adenocarcinoma.
“Results of a subgroup analysis of this trial showed that patients with PD-L1 CPS less than 10 did not appear to achieve as much of a benefit with the pembrolizumab combination. However, the emphasis we place on a subgroup analysis of a randomized study is a matter of further discussion,” Mukherjee said. “Based on the results of this trial, NCCN placed a category 1 recommendation on those with a CPS score of 10 or greater but since benefit was seen in all-comers, the FDA approval did not mention a CPS score.”
Of note, biomarker selection is key in this overall population of patients, as they will help better identify patients suitable for immunotherapy and avoid unnecessary toxicities among other individuals, he said.
References:
Chung HC, et al. Future Oncol. 2021;doi:10.2217/fon-2020-0737.
Jangigian YY, et al. Lancet Oncol. 2020;doi:10.1016/S1470-2045(20)30169-8.
Kato K, et al. Abstract LBA8_PR. Presented at European Society Medical Oncology Virtual Congress; Sept. 19-21, 2020.
Kelly RJ, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2032125.
Moehler M, et al. Abstract LBA6_PR. Presented at European Society Medical Oncology Virtual Congress; Sept. 19-21, 2020.
Mukherjee S. Immunotherapy in gastroesophageal cancers: How and when? Presented at: 39th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 3-5, 2021.
Collapse
Mukherjee S. Immunotherapy in gastroesophageal cancers: How and when? Presented at: 39th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 3-5, 2021.
Click Here to Manage Email Alerts