Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the importance of routine HER2 testing in gastric/gastroesophageal (GEJ) cancer. 

Currently, routine HER2 testing is offered at most academic centers because first-line trastuzumab (Herceptin) is a standard of care for patients with HER2-positive metastatic gastric/GEJ cancer, Janjigian explains. However, in some areas of the world and in the community setting, HER2 testing is less widely available in this space. 

Notably, about 20% to 30% of patients with HER2-positive gastric/GEJ cancer will lose HER2 expression after they progress on first-line trastuzumab, Janjigian says. As such, routine HER2 testing is needed to inform the optimal second- and third-line therapy for patients. This becomes more relevant as more HER2-directed agents are introduced to the space, concludes Janjigian.

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Yelena Y. Janjigian, MD, discusses the importance of routine HER2 testing in gastric/gastroesophageal cancer.  



Dr. Janjigian on the Importance of Routine HER2 Testing in Gastric/GEJ Cancer 

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the expanding treatment armamentarium in HER2-positive gastric cancer. 

Currently, trastuzumab (Herceptin) in combination with chemotherapy remains the first-line standard of care for patients with HER2-positive, metastatic gastric cancer based on the results of the phase 3 ToGA trial, Janjigian explains. Over the past few years, several clinical trials have yielded negative findings in this space, including those evaluating lapatinib (Tykerb) plus chemotherapy in the frontline setting, pertuzumab (Perjeta) plus trastuzumab in the frontline setting, and ado-trastuzumab emtansine (Kadcyla; T-DM1) in the second-line setting.

However, findings from the phase 2 DESTINY-Gastric01 trial showed an improvement in objective response rate and overall survival with the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with previously treated HER2-positive gastric cancer. Additionally, therapies, such as tucatinib (Tukysa) plus trastuzumab, margetuximab-cmkb (Margenza), and the combination of trastuzumab and pembrolizumab (Keytruda) are currently in the pipeline for HER2-positive gastric cancer, concludes Janjigian. 

Yelena Y. Janjigian, MD, discusses the expanding treatment armamentarium in HER2-positive gastric cancer. 



Dr. Janjigian on the Expanding Treatment Armamentarium in HER2+ Gastric Cancer 

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the emergence of new treatment options in esophageal and gastric cancer.

In 2020, a host of data have emerged in the field of esophageal and gastric cancer​. Moreover, an FDA approval for fam-trastuzumab deruxtecan-nxki (Enhertu) ​for the treatment of patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer is highly anticipated. In May 2020, the FDA granted the agent a breakthrough therapy designation for these patients who have received 2 or more prior lines of therapy, including trastuzumab (Herceptin). Patients with HER2-positive disease represent an unmet need in the space, Janjigian says.

 Notably, with the number of treatment options currently available, along with new approaches in the pipeline, it’s paramount for the field to become familiar with all relevant research. New findings ​from clinical trials can often be applied to practice on a more widespread level, Janjigian emphasizes.

Yelena Y. Janjigian, MD, discusses the emergence of new treatment options in esophageal and gastric cancer.

Dr. Janjigian on the Emergence of New Treatment Options in Esophageal and Gastric Cancer

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the importance of selecting ​an optimal first-line therap​y in gastric cancer.

Gastric cancer is a complex disease, ​and the field continues to evolve​, says Janjigian. Notably, ​updated data or a new trial emerges into the paradigm every 3 to 6 months, Janjigian explains.

Careful consideration is needed when selecting the frontline therapy for a patient with newly diagnosed gastric cancer, Janjigian says. Moreover, initial therapy selection can have a tremendous effect on the patient’s ​treatment journey ​and long-term survival. As such, individualized consideration into the ​optimal agent ​and dosing ​regimen are needed to maximize the ​patient's potential response, while avoiding toxicities and maintaining ​adequate nutrition.

Gastric cancer encompasses at least 4 to 5 different molecular​ly distinct subtypes; thus, experts are eager to understand more ​about the presentation of this disease and is hopeful for what the future holds, Janjigian concludes.

Yelena Y. Janjigian, MD, discusses the importance of selecting ​an optimal first-line therap​y in gastric cancer.








Dr. Janjigian on the Importance of First-Line Therapy Selection in Gastric Cancer

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the importance of biomarker testing in gastrointestinal (GI) cancers.

Biomarker testing can play a key role in personalizing and optimizing sequencing strategies for patients with metastatic GI cancer, Janjigian says. Notably, molecular profiling should be conducted early on so that HER2, PD-L1, and Epstein-Barr virus status can be determined. In addition, next-generation sequencing is beneficial in terms of looking at the tumor as a whole and understanding germline predisposition, Janjigian explains.

For example, in gastric cancer, targetable germline alterations are commonly found ​irrespective of family history. This identification can assist in the treatment selection process, Janjigian concludes.

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the importance of biomarker testing in gastrointestinal cancers.

Dr. Janjigian on the Importance of Biomarker Testing in GI Cancers 

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses updated results from the ​phase 2 DESTINY-Gastric01 trial​ in previously treated patients with HER2-positive gastric cancer.

The multicenter study was conducted in Asia where heavily pretreated patients ​with HER2-positive disease were randomized to receive either chemotherapy or fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu). Despite the challenges, the overall response rate was remarkable, says Janjigian. Notably, the overall response rate was 51% ​with T-DXd versus 14% with chemotherapy. The median overall survival was at 12.5 months ​and 8.4 months, respectively.

These data compare favorably to several other standards of care, Janjigian explains. Moreover, due to the exciting data, a breakthrough therapy designation was granted to T-DXd by the FDA for the treatment of patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

This would be extremely beneficial to our patients in the 3rd line setting, Janjigian exclaims. The risk of pulmonary toxicity is an area of concern with T-DXd as grade 5 treatment-related adverse events (TRAEs), including interstitial lung disease, have been observed in patients with HER2-positive breast cancer and colorectal cancer.

Yelena Y. Janjigian, MD, discusses updated results from the ​phase 2 DESTINY-Gastric01 trial​ in previously treated patients with HER2-positive gastric cancer.

Dr. Janjigian on Updated Results from the DESTINY-Gastric01 Trial in HER2+ Gastric Cancer

, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the rationale behind the plasma and tumor-based biomarker analysis of pembrolizumab (Keytruda) in combination with trastuzumab (Herceptin) and chemotherapy in HER2-positive metastatic esophagogastric cancer.

Patients on the trial experienced an unprecedented overall response rate (ORR) of 91%, according to Janjigian; this compared favorably with the historical control combination of chemotherapy and trastuzumab (Herceptin), as seen in the phase 3 ToGA study. In that study, chemotherapy plus trastuzumab demonstrated a 47% ORR in HER2-positive gastric cancer, says Janjigian.

Furthermore, the combination of pembrolizumab plus trastuzumab, capecitabine, and oxaliplatin resulted in durable progression-free survival, with 70% of patients progression free at 6 months, meeting the primary end point of the trial. The median overall survival in this population was 27 months, which was very impressive, according to Janjigian. Based on these data, the phase 3 KEYNOTE-811 study is accruing patients and the goal is to confirm the robust survival benefit seen with this approach.

Results from an analysis of tissue- and blood-based biomarkers conducted as part of the phase 2 study was presented at the 

. With this analysis, investigators were trying to determine how to predict which patients will respond and have durable responses to this treatment approach. Most patients will respond, says Janjigian; 100% of patients experienced a reduction in tumor burden. Since 16% of patients in this study experienced complete responses, it's important to determine which patients can potentially achieve cure with this combination in the long term, concludes Janjigian.

Yelena Y. Janjigian, MD, discusses the rationale behind the plasma and tumor-based biomarker analysis of pembrolizumab in combination with trastuzumab and chemotherapy in HER2-positive metastatic esophagogastric cancer.

Dr. Janjigian on Pembrolizumab Triplet in HER2+ Esophagogastric Cancer

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses data examining surgery plus extensive intraoperative peritoneal lavage (EIPL) versus surgery alone in patients with gastric cancer.

Unfortunately, were mostly negative studies were presented at the 2020 Gastrointestinal Cancers Symposium, says Janjigian. For example, a negative phase 3 study from Asia in surgical cases with gastric cancer was presented. No clear benefit was observed with peritoneal lavage or peritoneal-directed washings in patients with gastric cancer and cytology-positive disease. The question that repeatedly arises is, “Should more localized therapy be conducted to try and cure these patients?”

Patients enrolled were diagnosed with cT3/4 stomach cancer and undergoing curative resection. They were randomized to either surgery and EIPL or surgery alone. After a median follow-up of 29 months, the 3-year cumulative incidence of all-cause mortality was 23.1% and 23.3% for EIPL and surgery alone, respectively (HR, 1.09; 95% CI, 0.78-1.52, 

 =.615). The 3-year cumulative incidence of recurrence were 28.0% and 25.9%, respectively (HR, 1.01; 95% CI, 0.74-1.37, 

 =.947), and 7.9% and 6.6%, respectively, for peritoneal recurrence (HR, 1.33; 95% CI, 0.73-2.42; 

Data from this presentation suggest that these patients have advanced disease and unless patients are selected for specific biology in tumor subsets, the treatment is palliative in intent and no role for these peritoneal therapies exists, concludes Janjigian.

Yelena Y. Janjigian, MD, discusses data examining surgery plus extensive intraoperative peritoneal lavage versus surgery alone in patients with gastric cancer.

Dr. Janjigian on Extensive Intraoperative Peritoneal Lavage in Gastric Cancer

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses results from the phase III JAVELIN Gastric 100 study evaluating avelumab (Bavencio) in gastric or gastroesophageal (GEJ) cancer.

Although data from the phase III study were eagerly awaited, the agent was not found not improve overall survival (OS) as frontline maintenance following induction chemotherapy in patients with unresectable, locally advanced, or metastatic HER2-negative gastric or GEJ cancer, according to Janjigian.

Avelumab missed both of the trial’s OS-based primary end points. Specifically, the median OS was 10.4 months (95% CI 9.1-12.0) in the avelumab arm versus 10.9 months (95% CI 9.6-12.4) in the chemotherapy arm; the 24-month OS rates were 22.1% (95% CI 16.8-28.0) versus 15.5% (95% CI 10.8-20.9), respectively.

This was a relatively small study considering the question it was trying to answer regarding maintenance therapy, which has been a very exciting research question that has been postulated in gastric cancer, adds Janjigian. Unfortunately, overall, this was a negative study that essentially put a break on maintenance strategies in this disease, according to Janjigian.

Another study examining maintenance ipilimumab (Yervoy) was similarly negative, notes Janjigian. As such, the field needs to go back and really consider how to target this disease, determine what the appropriate therapy is, and how to best select patients based on biomarker studies, concludes Janjigian.

Yelena Y. Janjigian, MD, discusses results from the phase III JAVELIN Gastric 100 study evaluating avelumab in gastric or gastroesophageal cancer.

Dr. Janjigian on the JAVELIN Gastric 100 Study With Avelumab in Gastric/GEJ Cancer

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the improvement in efficacy and toxicity with patients with hepatocellular carcinoma (HCC) who are treated with bevacizumab (Avastin) and atezolizumab (Tecentriq) when compared with sorafenib (Nexavar).

Results from the ongoing phase III IMbrave150 trial, which were presented at the 2019 ESMO Asia Congress, showed that the combination of bevacizumab and atezolizumab had a favorable toxicity profile when compared with sorafenib in patients with HCC. However, grade 3/4 adverse events were more common in the combination arm (57%) versus the sorafenib arm (55%). The combination of bevacizumab and atezolizumab was better tolerated by patients, and there was also an improvement in quality of life.

The median OS has not yet been reached compared with 13.2 months for sorafenib. This is a new form of treatment that could change the landscape of HCC, says Janjigian.

Yelena Y. Janjigian, MD, discusses the improvement in efficacy and toxicity with patients with hepatocellular carcinoma who are treated with bevacizumab and atezolizumab when compared with sorafenib.
 

Yelena Y. Janjigian, MD

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