In a discussion with Targeted Oncology, Michael Gibson, MD, PhD, discusses the benefits of using a patient’s PD-L1 combined positive score to determine if they are given nivolumab and chemotherapy to treat their gastric cancer.
CASE
Targeted Oncology: What are some of the trials that make up relevant data for the use of nivolumab and chemotherapy in this patient population?
MICHAEL GIBSON, MD, PhD: Despite all the [approved] options for these patients, the data to support them are very repetitive. For patients with esophageal squamous cell carcinoma, [the trial that led to the approval of nivolumab and chemotherapy for these patients was] CheckMate 648 [NCT03143153].1 In both squamous and non-squamous disease KEYNOTE-590 [NCT03189719] led to the approval for pembrolizumab [Keytruda] plus chemotherapy.2
What was notable from the CheckMate 649 (NCT02872116) study outcomes?
The randomization of this trial was straightforward; [patients were on either] chemotherapy alone or nivolumab plus or minus chemotherapy, and the primary end points [were overall survival (OS) and progression-free survival (PFS) in patients with a PD-L1 combined positive score (CPS) of 5 or more].3 At 3-years [of follow-up], the median OS and PFS [in the combination arm] were higher for those with a CPS of 5 or more [compared with] the entire randomized population.4 [This was at 14.4 months (95% CI, 13.1-16.2) vs 13.7 months (95% CI, 12.4-14.5) and 8.3 months (95% CI, 7.0-9.3) vs 7.7 months (95% CI, 7.1-8.6), respectively].4 This showed the validity of CPS as a marker for this patient population.
How are the patient’s quality-of-life outcomes impacted by this combination?
Quality-of-life [measurements have] tremendous importance...and these were collected in the CheckMate 649 trial.... As the treatments went on, the numbers [corresponding to the patient's] quality of life got better.5 Looking at safety, just like in all the immunotherapy vs chemotherapy studies, the difference in toxicity is in the immune-related adverse events [irAEs]....3 There are irAEs that go away with [extra treatment] and there are ones that don’t.... I would be curious to see data that suggests the patients who are treated with prednisone got better [compared with] those who didn't, but I haven't been able to find those sort of data presented in that way.
References:
1. FDA approves Opdivo in combination with chemotherapy and Opdivo in combination with Yervoy for first-line esophageal squamous cell carcinoma indications. FDA. News Release. May 31, 2022. Accessed February 28, 2024. http://tinyurl.com/4my6bb54
2. FDA approves pembrolizumab for esophageal or GEJ carcinoma. FDA. News Release. March 22, 2021. Accessed February 28, 2024. http://tinyurl.com/y8khh4yz
3. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27-40. doi:10.1016/S0140-6736(21)00797-2
4. Janjigian YY, Ajani JA, Moehler M, et al. First-line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III CheckMate 649 trial. J Clin Oncol. 2024: JCO2301601. doi:10.1200/JCO.23.01601
5. Moehler M, Xiao H, Blum SI, et al. Health-related quality of life with nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric/gastroesophageal junction cancer or esophageal adenocarcinoma from CheckMate 649. J Clin Oncol. 2023;41(35):5388-5399. doi:10.1200/JCO.23.00170
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