Yelena Y. Janjigian, MD

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.

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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.

Author | Yelena Y. Janjigian, MD

Articles

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

Dr. Janjigian on Pembrolizumab Triplet in HER2+ Esophagogastric Cancer

Dr. Janjigian on Extensive Intraoperative Peritoneal Lavage in Gastric Cancer

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