Adverse Effects

Brain Cancer

HER2-Positive Breast Cancer

Triple-Negative Breast Cancer

Breast Cancer

Colorectal Cancer

Esophageal Cancer

Gastric Cancer

Liver Cancer

Pancreatic Cancer

Gastrointestinal Cancer

Bladder Cancer

Kidney Cancer

Prostate Cancer

Genitourinary Cancers

Cervical Cancer

Endometrial Cancer

Ovarian Cancer

Gynecologic Cancers

Head & Neck Cancer

Multiple Myeloma

Myelodysplastic Syndromes

Myeloproliferative Neoplasms

Hematologic Oncology

Vaccines

Infection

Leukemia

Non-Small Cell Lung Cancer (NSCLC)

Small Cell Lung Cancer (SCLC)

Lung Cancer

Lymphoma

Neuroendocrine Tumors

Oncology

Pediatric Cancers

Radiation Oncology

Sarcoma

Screening

Skin Cancer & Melanoma

Surgery

Thyroid Cancer

News

Global Bulletin

All News

FDA Approval Alert

Women in Oncology

Media

Expert Interviews

Around the Practice

Between the Lines

Face Off

From All Angles

Meeting of the Minds

OncView

Podcasts

Training Academy

Treatment Algorithms with the Oncology Brothers

Videos

Conferences

Publications

All Journals

Editorial Board

For Authors

Year in Review

Events

Frontline Forum

Satellite Sessions

CME/CE

Resources

Awareness Month

Interactive Tools

Nurse Practitioners/Physician's Assistants

Partners

Career Center

Subscribe

CancerNetwork is home to the journal Oncology & provides insights on the screening, early detection, diagnosis, treatment and prevention of cancers.

About

Advertise

CureToday.com

OncLive.com

OncNursingNews.com

TargetedOnc.com

Editorial

Contact

Terms and Conditions

Privacy

Do Not Sell My Personal Information

CancerNetwork - Oncology News and Clinical Expertise

Facebook

LinkedIn

Youtube

Spotlight

Clinical

Genitourinary Cancer

Gynecologic Cancer

Hematology

Skin Cancer

1rem

Topics

As part of our coverage of ASCO’s 2017 Gastrointestinal Cancers Symposium held January 19th to the 21st in San Francisco, today we are speaking with Dr. Geoffrey Ku, MD, a medical oncologist with Memorial Sloan Kettering Cancer Center specializing in gastrointestinal malignancies. At this year’s meeting, Dr. Ku will be participating in an education session on advances in systemic therapy for esophageal and gastric cancer.

Dr. Ku, your portion of the session will focus on immunotherapy. Immunotherapy is still somewhat new to the cancer scene, and is most commonly discussed in relation to melanoma, kidney, or lung cancers. How does research into immunotherapy for gastric and esophageal cancers compare with the progress in these other solid tumors? 

 Thanks for the question and I really appreciate the opportunity to discuss this. A part of the excitement is that while immunotherapy is certainly new the recognition is that in many different cancers it really is the most exciting development in last 20 or 30 years.

As you know, the premise is that we are giving drugs that essentially stimulate the immune system so that the immune system is able to recognize and attack cancer cells. These drugs were initially developed in melanoma, but over the space of 5 to 6 years there are now FDA-approved indications in many other common cancers including lung as well as bladder cancer. I would say that in esophageal and gastric cancer development of these drugs lags a little behind lung cancer, but there are certainly phase III studies that are ongoing.

In fact, at the Gastrointestinal Cancers Symposium there will be the results of a phase III study of one of these drugs that will be presented. At this point, we only have little bits of information, but the press release does suggest that it is a positive study that found clear benefit for one of the immune drugs versus placebo. That really is a milestone development in esophageal/gastric cancer.

Do any specific types of gastric or esophageal cancers or subgroup of patients appear to benefit more from immunotherapy approaches?

 That is certainly more than $64,000 question. It is the $640 million question. I think it is clear not only in esophageal/gastric cancer, but in other cancers that do respond to immune treatment that there are subgroups of patients who appear to derive more benefit than others. Certainly we think that one of the most helpful biomarkers, at this point, is a protein called PD-L1. PD-L1 is a target for many of these immune drugs. In esophageal/gastric cancer it is found about 40% of time. When it is present, it significantly increases the chance of shrinkage and response to these immune treatments. That is potentially one way to help select patients. Part of challenge of using PD-L1 is that even when it is not present there still are some patients who can benefit.

That is one important biomarker, but at the same time, we also know that, in general, the immune system is better able to recognize cancer cells that appear very abnormal. The more mutations that a cancer cell has the more likely it is to be recognized by the immune system. This remains an area of active development, but we are all trying to figure out how we can best figure out how abnormal cancer cells looks like, how many mutations they have.

Certainly, the thought is that markers like PD-L1, markers like the amount of mutations that are found in the cancer cells may allow us to fine tune who is and is not likely to benefit from these medications because while they are active, the reality is that they really only do benefit a minority of patients. They can have significant side effects, which involve inflammation of essentially any part of the body. That is what happens when the immune system becomes super activated.

Among the different immunotherapeutic approaches, research of immune checkpoint inhibitors have shown the most promise, what trials have looked into these drugs in gastrointestinal cancers and what have the results shown so far?

 There are a number of drugs that are all relatively similar. They all work by blocking a pathway known as PD-1/PD-L1. This is a pathway that we think helps to lower the immune system. We think that it is one way that cancer cells are able to evade the immune system after the immune system initially recognizes them. There are four or five different drugs that are being looked at and they are all antibodies. They are proteins that block this pathway. Representative drugs include pembrolizumab, nivolumab, and avelumab.

At this point in time, there are probably anywhere from five to seven, potentially even more, complementary phase III studies that are ongoing. As I mentioned, the one study that will be presented in about 10 days at the Gastrointestinal Cancers Symposium involves a drug called nivolumab, which blocks a protein called PD-1. In a study of about 450 patients-it was done mostly in East Asia-nivolumab helped patients live longer than patients who received placebo. Certainly, nivolumab is a leading contender, but pembrolizumab, which is a very similar drug, is also currently being looked at in multiple phase III studies, some of which are complete and potentially for which we will have results over the next 1 or 2 years.

Looking to the future, what areas are yet to be explored and what clinical trials are the most eagerly awaited in this area?

There are really many phase III studies that are ongoing. These are studies all in the advanced setting. Patients who have cancer that has spread in the first place, or cancer that recurred after a combination of surgery, chemotherapy, or radiation. There are studies in the first-line setting, meaning patients who have not received any previous treatment. There are studies in the second-line setting, meaning for patients for whom the cancer has grown on one treatment. They are either looking at these immune drugs on their own or they are comparing them to standard chemotherapy. Any number of these phase III studies have results that are eagerly awaited.

In terms of looking to the future, it is a combination of some of the things that we discussed. The one thing I would emphasize is that despite the promise and the excitement of these drugs, it is a relative minority of patients that benefit. Approximately only 15% of all patients benefit from these immune treatments. Part of the goal as we move forward is trying to identify biomarkers or tests that can help us to figure out who falls into the 15% of patients.

Careful patient identification to select patients who are most appropriate for the treatments so that we minimize exposing patients who are not likely to benefit from these treatments is definitely a priority. At the same time, the second generation studies, which are already slowly beginning, are beginning to look at combination strategies with the premise that potentially two drugs are better than one, or two ways of activating the immune system is better than one. This is an approach that is born out in other cancers, including melanoma and lung cancer, but the idea now is to begin to look at two drugs that activate the immune system or a combination of immunotherapy with chemotherapy, or even combining these drugs with radiation. There is some thought that if we treat a tumor with radiation and we are able to kill the tumor cells and the contents of the tumor cells are released, an immune system that is already activated is better able to recognize them.

These are all new strategies that are slowly underway. To the degree that immunotherapy has transformed the treatment of many other cancers, it is on the verge of transforming esophageal and stomach cancer. With the second-generation studies, we will see in the next 5 to10 years an improvement or an increase in the number of patients who will benefit and also an increased ability to better identify patients who will benefit.

I want to thank you again for speaking with us today and providing this update in immunotherapy in esophageal and gastric cancers. 

ASCO Gastrointestinal Cancer Symposium

Ahead of the 2017 ASCO Gastrointestinal Cancer Symposium in San Francisco, we spoke with Dr. Geoffrey Ku on the advances in systemic therapy for esophageal and gastric cancer.

Immunotherapy Treatments Only Just Emerging in Esophageal, Gastric Cancers

Results from the phase 3 MATTERHORN trial support the FDA’s designations for durvalumab in gastric/gastroesophageal junction cancers.

Durvalumab Earns Priority Review, Breakthrough Status in Gastric Cancer

Phase 1b data show antitumor activity with the givastomig combination across a wide range of CLDN18.2 expression.

Givastomig Regimen Yields Preliminary Activity in Gastric/GEJ Cancers 

Results from the phase 1a/b trial evaluating ADRX-0405 in various solid tumors, including gastric cancer, are expected to come in late 2025. 

FDA Grants Orphan Drug Designation to ADRX-0405 for Gastric Cancer

Investigators will present detailed results from the phase 3 FORTITUDE-101 trial at a future medical meeting.

Bemarituzumab Regimen Improves Survival in FGFR2b+ Gastric/GEJ Cancer

Subgroup analyses from the phase 3 CheckMate649 and KEYNOTE-859 clinical trials showed little OS difference between investigational and chemotherapy arms.

FDA Limits Pembrolizumab/Nivolumab in PD-L1–Low Gastric Cancer Indications

According to Ronan J. Kelly, deciding whether to give nivolumab- or durvalumab-based regimens in gastric cancers may rely on a patient’s frailty.

MATTERHORN Findings May Offer Additional Therapy Option in Gastric Cancers

In a conversation with CancerNetwork®, Ronan J. Kelly, MD, MBA, spoke about advice he would give regarding the integration of nivolumab (Opdivo) following chemoradiation in patients with esophageal/gastroesophageal junction (GEJ) cancers following a presentation of a 5-year analysis of the 

phase 3 CheckMate 577 study (NCT02743494)

2025 American Society of Clinical Oncology Annual Meeting.

Kelly is the director of oncology at the Charles A. Sammons Cancer Center and W.W. Caruth, Jr. Endowed Chair of Immunology at Baylor University Medical Center in Dallas, Texas.

He began by suggesting that findings from the phase 3 MATTERHORN trial (NCT04592913) evaluating the addition of durvalumab (Imfinzi) to fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) in the same patient population may offer a second immune checkpoint inhibitor for this patient group if approved, thereby expanding treatment options for patients.

 He further explained that a decreasing use of neoadjuvant chemoradiation in gastric and GEJ cancers may give way to perioperative treatment with the MATTERHORN regimen, which he claimed has shown to be “the better option.”

In patients with esophageal squamous cell carcinoma, he suggested that radiation may have a role to play, expressing that patients treated with chemoradiation and surgery followed by nivolumab elicited a 19-month improvement in overall survival. Furthermore, he remarked that for those with esophageal adenocarcinoma, the regimen evaluated in the phase 3 ESOPEC trial (NCT02509286), including perioperative chemotherapy, showed benefit in younger, fitter patients. He concluded by suggesting that clinicians may consider chemoradiation/nivolumab in more frail populations given their intolerance to surgery.

Up to now, we’ve had only 1 immune checkpoint inhibitor approved in [patients with esophageal/GEJ cancers], which was from adjuvant nivolumab. We looked at the data from the phase 3 MATTERHORN trial in the plenary session. It’s not FDA approved yet, but I think we all expect that will be the case. I think now we have options for our patients. If you look at where perioperative chemotherapy is going, and we’ve seen a decrease in the use of radiation in this setting, gastric and GEJ cancers shouldn’t be treated with neoadjuvant chemoradiation. The data are strong there; perioperative treatment is the better option there. With durvalumab now in the phase 3 MATTERHORN study showing those benefits over FLOT alone, I expect that will become the standard of care for GEJ and gastric [cancers].

In terms of esophageal squamous cell carcinoma, I think radiation still does have a big role to play. The CheckMate 577 study design with chemoradiation and surgery followed by a year of nivolumab is a standard of care in that disease setting. If you look at the squamous group, we had shown benefits there. There was a 19-month improvement in overall survival if you just looked at esophageal squamous [histology], so clearly this is still a standard of care.

Then, in that middle group, which [is] the esophageal adenocarcinomas, MATTERHORN did not look at that group, but we had previously seen a trial from Germany called the phase 3 ESOPEC trial, which showed a benefit of perioperative chemotherapy vs chemoradiation, although they did not compare it with chemoradiation followed by adjuvant nivolumab, which was the standard there. My take-home [message] there is we need to be a little careful.

In younger, fitter patients who can tolerate FLOT, I think that will become the new normal in esophageal adenocarcinoma. But there’s an older population who may be a bit frailer–– [those in] the community setting are struggling to give FLOT in a safe manner. There is clearly a learned behavior here in terms of cancer centers that are giving this, so I think for that [older] group, I would advise doctors to make a decision about tolerance of treatment.

Each individual oncologist will be in the best position to make that decision. What we don’t want is to give people treatment that then they get too frail or sick to tolerate a subsequent surgery. That’s not in the best interest of patients. Doctors will have a choice: In an older, frailer group, they may decide to do the CheckMate 577 [regimen], given the benefits we’ve shown with adjuvant nivolumab. In a younger, fitter patient population, they may decide to go with perioperative FLOT.

Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): first results of overall survival (OS) from CheckMate 577. 

 2025;43(suppl 16):4000. doi:10.1200/JCO.2025.43.16_suppl.4000

Janjigian Y, Al-Batran SE, Wainberg Z, et al. Event-free survival (EFS) in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). 

2025;43(suppl 17):LBA5. doi:10.1200/JCO.2025.43.17_suppl.LBA5

According to Ronan J. Kelly, MD, MBA, deciding whether to give nivolumab- or durvalumab-based regimens in gastric cancers may rely on a patient’s frailty.

Five-year follow-up revealed that patients treated with nivolumab vs placebo in the phase 3 CheckMate 577 trial experienced a “doubling” of survival.

Nivolumab Exhibits Enhanced DFS Outcomes in Resected Gastric Cancers

Ronan J. Kelly, MD, MBA, director of oncology at the Charles A. Sammons Cancer Center and W.W. Caruth, Jr. Endowed Chair of Immunology at Baylor University Medical Center in Dallas, Texas, spoke with CancerNetwork® about efficacy findings from a 5-year follow-up analysis of the 

 evaluating nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction cancer previously treated with chemoradiation

He presented these data in an oral session at the 

He began by outlining findings related to the primary end point of disease-free survival (DFS), expressing that after 5 years of follow-up, the median DFS favored the investigational therapy with an HR of 0.76. Additionally, he expressed that the separation of the Kaplan-Meier curves between the investigational and control regimens continued through 5 years of follow-up.

Furthermore, he expressed that distant metastasis-free survival, an exploratory end point, and overall survival (OS), a secondary end point, both numerically favored nivolumab, with respective HRs of 0.75 and 0.85. He concluded by explaining that although a clinically meaningful improvement was observed with OS, outcomes fell short of attaining statistical significance.

The primary end point of the [phase 3 CheckMate 577] study was disease-free survival. We’re now able to show 5 years of [follow-up]. It continued to show a clinically meaningful improvement for nivolumab vs placebo. With this longer follow-up, the median disease-free survival was 10.8 months in the placebo arm and 21.8 months in the nivolumab arm with the hazard ratio of 0.76 [while] maintaining that doubling of disease-free survival, which we’ve shown 5 years ago…. The shape of the curves shows that they separate at approximately 3 to 4 months. And if you look at the 5-year disease-free survival rate, it was 29% in the placebo group vs 37% in the nivolumab arm.

Distant metastasis-free survival was an exploratory end point in this study. Here again, we showed that nivolumab prevents distant metastasis. If we look at the [median] distant metastasis-free survival, it was 14.6 months with placebo vs 27.3 months with nivolumab, [with a] hazard ratio of 0.75. Again, the curves separate at that 4-month mark and remain separated. If you look at the 60-month or 5-year distant metastasis-free survival rates, it was 38% with nivolumab vs 29% with placebo.

Overall survival was a secondary end point, and here, for the first time, we showed the final results of overall survival after a minimum follow-up of 5 years, which was as per study design. What we showed was the median overall survival was longer with nivolumab vs placebo, 16.4 months longer, with a median OS of 35.3 months [with] placebo vs 51.7 months with nivolumab. Also, the 5-year overall survival rates were higher at 41% with placebo [and] 46% with nivolumab, suggesting a clinically meaningful improvement in overall survival, although statistical significance was not met with a hazard ratio of 0.85.

Patients treated with nivolumab in the phase 3 CheckMate 577 trial were less likely to experience progression-related treatment discontinuation vs placebo.

No Deaths Observed Related to Nivolumab in Resected Gastric Cancers

No nivolumab (Opdivo)-related deaths were observed among patients with resected esophageal or gastroesophageal junction cancer previously treated with chemoradiation in the 

phase 3 CheckMate 577 study (NCT02743494),

Kelly, director of oncology at the Charles A. Sammons Cancer Center and W.W. Caruth, Jr. Endowed Chair of Immunology at Baylor University Medical Center in Dallas, Texas, spoke with CancerNetwork® about efficacy findings from the phase 3 study as well as key findings regarding patient characteristics and safety insights. He exhibited findings from the study in an oral presentation he gave at the 

2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

He began by describing the baseline characteristics for patients enrolled in the trial, explaining that most patients had esophageal cancer and that the most common histology was adenocarcinoma. He further remarked that most patients had node-positive disease, a poor prognostic factor, as well as histologically “hot” tumors, or ones with a PD-L1 combined positive score (CPS) of 1 or greater.

Kelly then described findings from the trial, highlighting that all patients had concluded therapy, with nearly half successfully completing treatment. He further expressed that disease progression occurred at a greater rate among patients treated with placebo vs nivolumab, with both arms experiencing a similar duration of treatment and number of doses. He concluded by explaining that more deaths occurred in the placebo arm vs the nivolumab arm and that no deaths were observed that were attributable to nivolumab treatment.

The [phase 3 CheckMate 577] data that we showed at the ASCO Annual Meeting had a data cutoff [date of] November 7, 2024. The median follow-up time was 78.3 months, and the minimum follow-up was 5 years. In terms of the baseline characteristics for patients who [were enrolled] in the study, the salient points are that [regarding] tumor location, 59% had esophageal cancer and 41% had gastroesophageal junction cancer. Adenocarcinoma was the predominant histology, with 71% of patients having adenocarcinoma [and] 29% having squamous cell carcinoma.

The poor prognostic factor of lymph node–positive disease occurred in 58% of the patients. And then we looked at PD-L1, broken down into both TPS [tumor proportion score] and CPS, and we know in this disease setting CPS is now the better assessment of PD-L1 status. Here, for the first time, we’ve shown that approximately 10% of patients had immunologically cold tumors defined as a CPS of less than 1 and the remaining patients had [a CPS of] greater than 1, or immunologically hotter tumors, so that was also interesting information.

In terms of exposure and disposition, there were no patients currently on treatment with the study drug. Forty-nine percent completed treatment, and then if we look at those who discontinued treatment, 29% [experienced] disease progression in the nivolumab arm whereas 44% [experienced] disease progression in the placebo arm. The median duration of treatment and the median number of doses were similar across both arms. In terms of death, we [observed] more deaths due to disease progression [with] placebo vs the nivolumab arm and there were no [nivolumab-related] treatment deaths.

Prolonging systemic therapy in patients with gastric or gastroesophageal junction cancers may offer better outcomes than radiation therapy.

Radiation Therapy Does Not Improve Survival in Gastric/GEJ Cancers

CancerNetwork® spoke with Yelena Y. Janjigian, MD, chief attending physician of the Gastrointestinal Medical Oncology Service at Memorial Sloan Kettering Cancer Center, about developments in gastric or gastroesophageal junction (GEJ) cancers that she believes has the potential to change clinical practice.

Highlighting results from 2 clinical trials—the phase 3 TOPGEAR (NCT01924819) and the phase 3 ESOPEC (NCT02509286) trials—Janjigian stated that radiation therapy in patients with gastric and GEJ cancers will not improve survival in this population.

Furthermore, she expressed that for immunotherapy in the perioperative setting, the fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) regimen was the optimal therapy. She added that in the event that FLOT was unable, dose reductions or the removal of docetaxel were viable treatment strategies. Furthermore, she advised against the use of another combination, known as the CROSS regimen, which is composed of paclitaxel plus carboplatin (CarboTaxol) plus radiation, in patients with gastric or GEJ cancers.

Janjigian explained that patients should not be rushed to undergo radiation therapy if they are unable to receive an R0 resection, instead suggesting prolonged systemic therapy with either a triplet or a doublet regimen with immunotherapy. Only after the disease biology declares itself should one consider performing surgery. She concluded by emphasizing that FLOT with durvalumab (Imfinzi) is the optimal regimen to treat this systemic disease in the perioperative setting.

Other developments in gastric and esophageal cancer that are critical to recognize are that we have now had 2 randomized studies published in the 

, just in the past year: the phase 3 TOPGEAR study and the phase 3 ESOPEC study showing that radiation does not improve survival in these patients. Radiating the gastroesophageal junction or stomach will not help your patients live longer.

The critical piece to [remember] is that you cannot radiate with FLOT, and if you are going to use immunotherapy in the perioperative setting, FLOT is the best option. If the patient is not able to get FLOT, if you want to dose reduce once you get started or drop docetaxel, that’s okay. One important factor to [remember] is that for adenocarcinoma, the CROSS regimen, or [paclitaxel plus carboplatin (CarboTaxol)] plus radiation, should never be used. I have not used this regimen in over 6 years. That [is an] important development: that radiation does not improve survival.

If the patient is not able to get a complete resection or R0 resection––sometimes oncologists say, “we radiated because the R0 section was not possible.” That’s not the patient that you should be rushing to the [operating room] with; radiation will not help this patient live longer. You need to prolong systemic therapy, perhaps starting with either a triplet with immunotherapy or a doublet with immunotherapy. Only once the disease biology declares itself you could consider doing surgery. 

The reason why the R0 resection rates are [higher] with radiation but do not translate to survival benefit is because this disease is systemic in nature. If you do not recognize that you are doing your patients a disservice and are ignoring the big factor that in patients who [receive radiation], R0 resection does not translate to survival benefit, that is the critical point. We need to treat systemic disease, and in the perioperative setting, FLOT plus durvalumab offers that important option.

Leong T, Smithers BM, Michael M, et al. Preoperative Chemoradiotherapy for Resectable Gastric Cancer. 

 2024;391(19):1810-1821. doi:10.1056/NEJMoa2405195

Hoeppner J, Brunner T, Schmoor C, et al. Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer. 

 2025;392(4):323-335. doi:10.1056/NEJMoa2409408

Most adverse effects observed in combination therapies for gastric cancers are associated with chemotherapy, according to Yelena Y. Janjigian, MD.

Durvalumab Plus FLOT May Not Significantly Increase AEs in Gastric Cancer

Most adverse effects (AEs) observed in previously published interim 

 results, assessing durvalumab (Imfinzi) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT), come from chemotherapy, according to Yelena Y. Janjigian, MD.

CancerNetwork® spoke with Janjigian, chief attending physician of the Gastrointestinal Medical Oncology Service at Memorial Sloan Kettering Cancer Center, about how the AE profile of durvalumab in combination with FLOT compared with that of chemotherapy alone in patients with resectable locally advanced gastric and gastroesophageal junction (GEJ) cancers.

She initially expressed that previously exhibited interim results from the phase 3 MATTERHORN trial showed that chemotherapy accounted for the majority of AEs in patients receiving durvalumab plus FLOT. Additionally, she added that immune-related AEs from anti–PD-1 or anti–PD-L1 agents happen infrequently but may be serious if observed.

Janjigian reiterated the idea that chemotherapy accounted for most AEs with combination therapy by highlighting results from the phase 2/3 FLOT-4 trial (NCT01216644).

Furthermore, she touched upon potential immune-related AEs, as well as skin toxicities, before explaining that the greatest difficulty regarding the safety profile of the durvalumab/FLOT regimen will be in administering FLOT safely.

Additionally, Janjigian supported the utilization of dose reduction and antiemetics such as olanzapine (Zyprexa) for AE management in this patient population, particularly dose reduction with or without growth factor support to help mitigate white blood cell count decreases. Citing previous success with managing the safety profile of adjuvant nivolumab with chemotherapy in patients with a high risk of recurrence from gastric or GEJ cancers, she suggested that the same could be expected from the durvalumab combination regimen in MATTERHORN.

Previous safety results from the phase 3 MATTERHORN trial revealed that the safety profile of durvalumab and FLOT were comparable with prior reports of each respective agent.

In terms of the [adverse] effects of chemotherapy in general, we know from the metastatic setting and also from the data that were already presented from the MATTERHORN study—which is [assessing] the FLOT plus durvalumab combination–that most of the adverse effects come from chemotherapy. The immune-related [adverse] effects from anti–PD-1 or anti–PD-L1 agents are relatively rare but could be serious.

When we think about a triplet combination, most of the [adverse] effects are from the chemotherapy because you are giving them fluoropyrimidine, oxaliplatin, and docetaxel. If an oncologist is able to give these drugs and has done that in their practice for quite some time—which we have; the [phase 2/3] FLOT-4 data came out years ago, and since then, those of us that see this disease have been using FLOT—the addition of durvalumab does not cause [many adverse] effects.

You could have immune-related [adverse] effects, which can commonly affect the skin, or other mild [adverse] effects. You could have endocrinopathies, thyroid abnormalities, and glucose metabolism abnormalities. But most of the [adverse] effects are well managed. The steepest learning curve will be managing and [administrating] FLOT safely. Certainly, that’s doable.

Dose reductions are our friend and our patients’ friend, [as well as] antiemetics––using drugs like olanzapine as an antiemetic per the ASCO guidelines. Perhaps using dose reductions and/or a growth factor support for a patient who will [experience] decreases in white blood cell count will be important.

Suffice to say, the data suggest that you could do it––that’s what we have already seen. Durvalumab maintenance, [which patients continue for 1 year following surgery], is also part of what the patients are already getting used to because of the culture of high-risk disease recurrence. We have done that with adjuvant nivolumab now, and so we do not anticipate any issues with that approach.

Gastric Cancer

Latest News