Complexity in GI Cancer: Questions Are Answered in Gastroesophageal Cancer, Remain in HCC

As findings from the phase 3 ESOPEC trial (NCT02509286) have demonstrated that radiation therapy may not be necessary for most patients with early-stage gastroesophageal cancers, chemotherapy-only regimens and investigations of immunotherapies are at the forefront, according to Tanios S. Bekaii-Saab, MD, FACP.

During the 2024 ASCO Annual Meeting, investigators presented updated data from ESOPEC which revealed that perioperative chemotherapy with docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT protocol) improved overall survival (OS) compared with neoadjuvant chemoradiation (CROSS protocol) for patients with resectable esophageal cancer. At a median follow-up of 55 months, patients in the intention-to-treat population who received the FLOT protocol (n = 221) achieved a median OS of 66 months (95% CI, 36-not evaluable) compared with 37 months (95% CI, 28-43) among those who received the CROSS protocol (n = 217; HR, 0.70; 95% CI, 0.53-0.92; P = .012).1

In an interview with OncLive®, Bekaii-Saab, highlighted recent data that have impacted the gastrointestinal (GI) cancer treatment landscape, specifically in gastroesophageal cancer and hepatocellular carcinoma (HCC). He also added that the readout of positive data from the phase 3 Checkmate-9DW trial (NCT04039607) has raised the question of whether a VEGF inhibitor plus immunotherapy or checkpoint inhibitors targeting CLTA-4 plus immunotherapy is the optimal regimen for patients with HCC.

Bekaii-Saab is the leader of the gastrointestinal cancer program at the Mayo Clinic Comprehensive Cancer Center as well as the medical director of the Cancer Clinical Research Office and vice chair and section chief for medical oncology at Mayo Clinic in Phoenix, Arizona.

OncLive: What conversations should clinicians have with multidisciplinary colleagues when treating patients with GI cancers?

Bekaii-Saab: GI malignancies have become quite complex, and the role of a medical oncologist is central to [multidisciplinary team] discussions. For instance, [in] HCC we were a secondary thought approximately 10 to 15 years ago, and today we’re central—we are treating patients in the more advanced setting, bringing many to locoregional therapies, and are able to bring some patients to transplantation.

[Therefore, it has] become much more complex for medical oncologists as we try to navigate the complexities of the different diseases we treat. For instance, a plenary session at ASCO 2024 [in resectable esophageal cancer] looked at the value of radiation with chemotherapy vs chemotherapy, both followed by surgery, and it appears that most patients [with] early-stage gastroesophageal cancers probably do not need any more radiation [therapy]. That discussion is important to have with our radiation oncology colleagues because they still think there may be some patients who benefit from radiation; [perhaps] chemotherapy/radiation may be an option [in] older patients who are frail [and] not able to go through treatment with FLOT.

Also, understanding where immunotherapy plays a role [is] important. At least in the earlier stages of disease, but even for certain patients in the later stages of the disease, having the multidisciplinary team involved in the discussions at all points for patients to optimize their likelihood of surviving cancer [is crucial].

What has been the impact of the recent data from the ESOPEC trial on clinical practice?

There are several trials that are impactful in the sense [that] some will change the standard [of care] quite a bit and others will add options that we need to [consider]. The most impactful one is the [ESOPEC trial examining] FLOT vs [CROSS because] that’s a study that essentially tells us that radiation is not indicated for most, if not all, patients with early-stage gastroesophageal cancers. That’s impactful because that’s a shift in the paradigm that’s been, mostly in the US at least, [a big part of care] unlike in Europe. Europe has been [using] a chemotherapy mostly treatment whereas in the US we’ve adopted radiation as a standard part of our treatment in early-stage esophageal cancer. That’s going to completely shift the paradigm and the discussion with patients to a chemotherapy only option and [there are] more studies with adjuvant immunotherapy coming through [as well].

What clinical trial data are generating excitement in HCC?

The Checkmate-9DW study with ipilimumab [Yervoy] and nivolumab [Opdivo] was positive [and] the question now for the community practitioner is [with] the option of a VEGF [inhibitor] plus immunotherapy or checkpoint inhibitors [targeting] CLTA-4 plus immunotherapy, how do you pick between the 2? Atezolizumab [Tecentriq] plus bevacizumab [Avastin] remains dominant so far [for] that patient population where a clinician would think to prioritize a CTLA-4 inhibitor plus a PD-1 or PD-L1 agent. Which one would we go with? Would we go with the STRIDE regimen with tremelimumab [Imjudo] and durvalumab [Imfinzi] or with ipilimumab and nivolumab?

There are pluses and minuses with each, and the question is why would you pick those for this patient population vs atezolizumab/bevacizumab? That enriches the discussion and also presents some dilemma for community practitioners and other treating physicians/oncologists. How do you [consider] each of these options and how do you individualize [treatment] at the level of each patient? That’s making things more complex.

The phase 3 CheckMate 8HW [trial (NCT04008030) in colorectal cancer] suggested that the addition of a CTLA-4 inhibitor, ipilimumab, to nivolumab is better than chemotherapy—a lot of questions remain including whether we need that CTLA-4 inhibitor. The study has not reported yet on the comparator nivolumab [monotherapy arm], which brings up the debate of what is the value of adding a more toxic [as well as] expensive agent, and is it worth it for the patient.

Reference

1. Hoeppner J, Brunner T, Lordick F, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial). J Clin Oncol. 2024;42(suppl 17):LBA1. doi:10.1200/JCO.2024.42.17_suppl.LBA1