Study reveals treatment patterns and raises new questions across gastrointestinal cancers


Jimmy Huang, M.D.

The therapeutic advances achieved so far for patients with gastrointestinal (GI) cancer are a direct result of the work of multidisciplinary experts in this field and face a variety of unsolved problems. Nevertheless, we continue to work together to achieve our common goal of improving and enhancing patient care. Outcome according to Jimmy Hwang, MD.

“cancer [care]perhaps more than any other disease, [requires] team [effort]’” Huang said in the following interview. on live® The State of the Science Summit™ on gastrointestinal cancer he chaired. “With that team working together, we have seen progress, maybe not as fast as we would have liked, but we are making progress.”

In an interview, Hwang discussed findings supporting the use of immunotherapy in hepatocellular carcinoma (HCC) and biliary tract cancer, potential benefits of antibody-drug conjugates in metastatic colorectal cancer (mCRC), esophageal squamous cell carcinoma, In the wake of unmet needs in (ESCC) and rectal cancer, and changes in standards of care, the increasingly important role of multidisciplinary approaches to addressing patient needs at all stages of treatment becomes increasingly important. has become

Phase 2 DESTINY-CRC01 trial (NCT03384940) showed efficacy of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2 immunohistochemistry (IHC) 3+ or IHC2+/in situ hybridization-positive mCRC . – increased by 62.4 weeks, eliciting an overall response rate of 45.3% (95% CI, 31.6%-59.6%).1 Hwang emphasized the importance of these results in the larger colorectal cancer (CRC) treatment paradigm. He also found that the addition of durvalumab (Imfinzi) to gemcitabine and cisplatin improved median overall survival by 12.8 months (95% CI, 11.1-14.0) vs. 11.5 months (95% CI, 10.1-12.5) compared to placebo. + gemcitabine and cisplatin.2

Hwang is a medical oncologist at Atrium Health’s Levine Cancer Institute in Charlotte, North Carolina.

on live®: Presentation by Alaa Muslimani, MD, Levine Cancer Institute, on Updates to Treatment of HER2-Positive mCRC: How DESTINY-CRC01 Study Results Support the Use of Trastuzumab Derctecan in Patients With Advanced HER2-Positive Disease disease?

fan: In patients with HER2-positive CRC, the findings are somewhat trivial in the sense that trastuzumab deruxtecan appears to have activity and therefore certainly suggests that it may be useful in these patients. bottom. The results were impressive enough to corroborate the data we’ve seen with other agents.

Caio Max Sao Pedro Rocha Lima, M.D., Ph.D., of Atrium Health Wake Forest Baptist Medical Center in Winston-Salem, NC, discussed novel treatment strategies in HCC. What are the limitations of first-line treatment options for this population of patients?

As of March 2023, many exciting new options are available outside the context of clinical trials for patients with well-preserved liver function, and more may emerge in the future.Emergence of Molecular Immunotherapy, Combination of Immunotherapy [agents] with other immunotherapies [agents] or immunotherapy [agents] Concomitant use with a VEGF inhibitor was beneficial compared to the previous standard of oral TKI. [outcome]but also in terms of total toxicity and tolerability, [which is] almost equally important.

One of the biggest challenges we have in this area is that this is a well-selected patient group, but the best for patients who don’t fit all of the nice, neat little boundaries that we’ve had in clinical trials. What are the treatment options for The reality is that immunotherapy has not been proven to be safe or tolerable in these patients. This is an important next step for the following patient groups: [around] 30% to 40% of all HCC patients.

Regarding the presentation on the role of immunotherapy in ESCC by Mohamed Salem, MD, Levine Cancer Institute, which biomarkers have not yet been determined in this field?

For esophageal squamous cell carcinoma, there are no definitive biomarkers for treatment. PD-L1 is the one we think he is, and certainly in adenocarcinoma of both the esophagus and stomach. [cancers, but] It is not clear that it is an important biomarker for ESCC.

Kunal Kadakia, M.D., Ph.D., of the Levine Cancer Institute, shared an update on pancreatic cancer. What is the importance of biomarker germline testing in predicting response to platinum-based therapy in pancreatic cancer?

The data clearly demonstrate that germline testing may help identify patients who respond to platinum-based therapy, and that it has potential benefits over other treatments thereafter. biomarker indication [approach] There is a germline test for pancreatic cancer.

Vernon Mackie, M.D., Ph.D., Levine Cancer Institute, described recent advances in advanced biliary tract cancer. What questions remain unanswered by findings from the TOPAZ-1 study?

TOPAZ-1 is an interesting study in terms of its results. The important thing for me, and for my patients, is to add immunotherapy. [agent] Like durvalumab and standard chemotherapy, patients were able to live longer than those who received chemotherapy alone. There are still questions about the optimal timing of the combination, the duration of the combination. But regardless of these important and nuanced issues, the addition of immunotherapy clearly improves patient survival.

Regarding the presentation on Surgical Perspectives in Rectal Cancer by Joshua Hill, MD, MS, Levine Cancer Institute, what are the most important aspects of multimodality therapy that can improve outcomes for patients in this population?

A growing body of data suggests that both the treatment and subsequent management of patients with locally advanced rectal cancer, regardless of biomarker choice, require a multimodal approach to achieve the best outcome. increase.Even in patients with mismatch repair deficiency [dMMR] Diseases that may benefit from immunotherapy alone still need to be monitored and are part of multidisciplinary care. seems to be important for obtaining the best possible results. [phase 2/3] PROSPECT Trial [NCT01515787].

What are your key messages to your colleagues about the current state and future direction of gastrointestinal cancer care?

The good thing about this group’s argument is that we’ve never seen as many home runs as we’ve seen with some other diseases and dMMR rectal cancer. [we have] A collection of data representing the efforts of thousands [researchers] And thousands of patients show us the progress we’ve made in a variety of diseases.Each step is an improvement in a patient’s life. Its progress required the support and cooperation of people from various fields.

Gastrointestinal oncology is a broad field and we are making progress in a wide range of areas. but, [we will] Continued efforts are needed across these areas to continue to improve as we have done in the past. We want to make sure these benefits reach all patients, not just those who are healthy enough to participate in clinical trials.

What gastrointestinal cancer research is currently underway at the Levine Cancer Institute that interests you most?

[We have] There is some interesting research going on here.We would love to see more studies for patients without disease that are candidates for targeted therapy. [trials] We are preparing to open one that includes targeted therapy for a smaller group of patients.

We are part of a Phase 1 expansion cohort [for the phase 1b/2 CodeBreak 101 trial (NCT04185883)] For patients with metastatic colon cancer class G12C– mutation. [This trial is combining] sotrasive [Lumakras] Panitumumab and [Vectibix]seeking to see if targeting that escape mechanism could improve outcomes, as has been seen in several other early-stage studies.

One of the other interesting studies was [the phase 3 BREAKWATER trial (NCT04607421)] in patients with Bluff– mutated [CRC]where we know encorafenib [Braftovi] plus cetuximab [Erbitux] Lateline settings can improve outcomes. [We are] I’m trying to check if I’m targeting [BRAF] Initial settings are expected to provide improved outcomes and an improved toxicity profile over standard chemotherapy.

References

  1. Yoshino T, Di Bartolomeo M, Raghav KPS, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in HER2-expressing metastatic colorectal cancer (mCRC) patients (pts): a phase 2, multicenter, open-label study (DESTINY- CRC01) final result. J Clin Onkol2022;40(suppl 4):119.doi:10.1200/JCO.2022.40.4_suppl.119
  2. Durvalumab in combination with gemcitabine and cisplatin in Oh DY, He AR, Qin S and other advanced biliary tract cancers. NEJM EvidMore.2022;1(8).doi:10.1056/EVIDoa2200015



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