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High Response Rate in HER2+ Esophagogastric Cancer

SAN FRANCISCO — Almost 90% of patients with metastatic HER2-positive esophagogastric cancer had objective responses following induction therapy with pembrolizumab (Keytruda), trastuzumab (Herceptin), and chemotherapy, according to a small study reported here at the Gastrointestinal Cancers Symposium.

The induction led to an overall response rate of 87% in 32 evaluable patients. Historical data for similar patients treated with chemotherapy alone showed a 47% response rate. Progression-free survival at 6 months — the primary endpoint — was 67%, and 35 evaluable patients had an estimated 12-month overall survival of 76%.

“I hope that we were clear that there is some synergy and benefit for this combination in metastatic gastric and G-junction tumors,” said Yelena Y. Janjigian, MD, of Memorial Sloan Kettering Cancer Center in New York City.

Patients eligible for the trial had untreated stage IV HER2-positive gastric or gastroesophageal junction adenocarcinoma, irrespective of PD-L1 expression status. In 26 patients evaluable for PD-L1 status, 12 were positive and 14 were negative. Confirmation of HER2 status at enrollment was not required, and six patients were found to have HER2-negative tumors.

PD-L1 expression status did not influence response to the induction regimen, said Janjigian. In contrast, ERBB2 nonamplification by next-generation sequencing was associated with a shorter duration of response.

Combination Active in HCC, Biliary Tract Cancer

Combined immune checkpoint inhibition led to disease control rates of 70% and 50% in two small cohorts of patients with unresectable advanced hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), respectively.

Two of 10 patients with HCC had partial responses and five had stable disease with the combination of CTLA-4 inhibitor tremelimumab and the PD-L1 inhibitor durvalumab (Imfinzi). One of 12 patients with BTC had a partial response and five others had stable disease, reported Charalampos S. Floudas, MD, of the National Cancer Institute in Bethesda, Maryland.

The trial design excluded patients with prior immunotherapy; prior systemic therapy, large-field radiotherapy, or surgery within the previous 2 weeks or receipt of an investigational agent within the previous 28 days; prior liver transplant; or a history of autoimmune disease.

Two patients each developed hyponatremia and lymphopenia. No other adverse events occurred in more than one patient, and three patients had grade ≥3 adverse events.

The clinical activity of the combination was promising, given the poor prognosis for HCC and BTC (5-year overall survival rates of <20% and <10%, respectively), Floudas and colleagues concluded in a featured poster presentation.

Short-Course Neoadjuvant CRT Safe, Feasible for Rectal Cancer

Total neoadjuvant therapy (TNT) with short-course radiotherapy (SC-TNT) proved to be at least as effective as conventional chemoradiation (CRT) for locally advanced rectal cancer, according to a retrospective comparison of the two strategies.

SC-TNT led to tumor downstaging more often than CRT did by two different assessments: pathologic complete response (25% of 152 patients vs 19% of 236 CRT-treated patients) and low neoadjuvant rectal score (36% vs 28%).

“Neither of these differences is statistically significant, but we do believe these trends are moving toward a significant difference, with higher downstaging achieved by the short-course regimen,” said William Chapman, MD, of Washington University in St. Louis.

Recurrence rates were similar over comparable follow-up durations (14.3% vs 14.9%), as was disease-free survival (DFS).

SC-TNT achieved outcomes similar to the CRT group despite having higher-risk patients, Chapman noted. The SC-TNT cohort had significantly more patients with stage III (77.0% vs 67.4%, P=0.04) and N2 disease (36.8% vs 17.4%, P<0.01), as well as fewer low tumors (33.1% vs 55.1%, P<0.01). A DFS analysis limited to lower-risk patients produced a trend in favor of SC-TNT.

The SC-TNT strategy, which has become standard care at Washington University, the authors noted, consists of hypofractionated radiation therapy (~25 Gy dose in five fractions) followed by 3 to 4 months of oxaliplatin-based chemotherapy, and then surgery. The regimen reduces total treatment time by about 2 months compared with standard CRT, which consists of a 50 Gy radiation dose in 25 to 28 fractions with concurrent chemotherapy followed by surgery and adjuvant chemotherapy.

The short-course regimen also has been better tolerated, said Chapman.

Janjigian disclosed relationships with Bristol-Myers Squibb, Lilly, Merck, Merck Serono, Pfizer, Amgen, Bayer, Boehringer Ingelheim, Genentech, and Roche. The study was sponsored by the Memorial Sloan Kettering Cancer Center.

Floudas disclosed a relationship with Illumina; the study was sponsored by the National Cancer Institute.

Chapman disclosed a relationship with Allergan.