Photo courtesy © ASCO/Scott Morgan 2019

Compiled by Alexey Rumyantsev, MD in the Department of Clinical Pharmacology and Chemotherapy of the N.N. Blokhin National Medical Research Center of Oncology, RakFond’s grantee, IDEA (International Development and Education Award) awardee and this year’s presenter at the ASCO meeting.

MAINTENANCE TREATMENT WITH OLAPARIB IN PATIENTS WITH PANCREATIC CANCER: POLO TRIAL

Aim of the study: to evaluate the efficacy of maintenance treatment with olaparib in patients with germline BRCA-mutated metastatic pancreatic cancer.

Study design: randomized multi-center phase III trial. Patients with germline BRCA-mutated pancreatic cancer, who had received the first-line platinum-based chemotherapy, were enrolled. Patients were randomized at 3:2 ratio to olaparib 300 mg BID or placebo. Treatment continued until progression or unacceptable toxicity.

Results: 154 patients were randomized. Patients’ characteristics were well balanced between the arms. Median progression-free survival was 7.4 months in the olaparib arm vs. 3.8 months in the placebo arm (hazard ratio, HR 0.53; p = 0.0038). After 24 months of treatment, no progression was seen in 22% and 10% of patients, respectively. No difference in overall survival was demonstrated at the interim analysis (the data is not sufficiently mature).

Why it is important: metastatic pancreatic cancer has unfavorable prognosis. Germline BRCA mutations are detected in 4-7% of patients with this disease, however, improvement of treatment outcomes even in a small proportion of patients can become an important step on the route to develop novel therapeutic regimens.

Detailed study results:

Kindler HL et al. Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial. https://meetinglibrary.asco.org/record/174488/abstract.

PEMBROLIZUMAB VS. CHEMOTHERAPY IN THE FIRST-LINE TREATMENT OF GASTRIC CANCER: RESULTS OF THE PHASE III KEYNOTE-062 STUDY

Aim of the study: to compare the efficacy of pembrolizumab and chemotherapy in the first-line treatment of advanced gastric or gastroesophageal junction cancer.

Study design: randomized phase III study to compare the efficacy of immunotherapy with pembrolizumab (anti-PD-1 monoclonal antibody) and standard chemotherapy in patients with advanced gastric cancer. Patients were randomized at the 1:1 ration to pembrolizumab 200 mg every three weeks (until disease progression) or chemotherapy (cisplatin + capecitabine or fluorouracil) with a placebo instead of pembrolizumab.

Results: 506 patients were randomized; patients’ characteristics were well-balanced between the arms. Median overall survival in the general study population was 10.6 months in the pembrolizumab arm vs. 11.1 months in the chemotherapy arm (HR 0.91; p = 0.162). However, among PD-L1+ patients (CPS≥10), median overall survival was 17.4 months vs. 10.8 months, respectively (HR 0,69).

Why it is important: the study should be formally declared negative since its primary endpoint wasn’t reached. However, among the patients with high PD-L1 expression, pembrolizumab demonstrated higher efficacy vs. chemotherapy, which provides a rationale for further research of this drug in gastric cancer.

Detailed study results:

Tabernero J et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. https://meetinglibrary.asco.org/record/173187/abstract.

NEOADJUVANT CHEMOTHERAPY FOR COLON CANCER: RESULTS OF THE PHASE III FOxTROT TRIAL

Aim of the study: to evaluate the efficacy and safety of neoadjuvant therapy in patients with colon cancer.

Study design: patients with T3-4, N0-2, M0 were enrolled. Patients were randomized at the 2:1 ratio to the neoadjuvant chemotherapy with oxaliplatin and fluoropyrimidines for 6 weeks or control surgery. After surgery, all patients received adjuvant therapy for 24 weeks.

Results: 1052 were randomized; patients’ characteristics were well balanced between the arms. In the neoadjuvant chemotherapy arm, the risk of incomplete resection (not achieving R0) was decreased (4.8% in the neoadjuvant chemotherapy arm vs. 11.1% in the control surgery arm), with a lower risk of postoperative complications. The trend toward improved relapse-free survival was seen in the neoadjuvant chemotherapy arm (HR 0,75; p = 0,08).

Why it is important: despite the fact that the trial hasn’t demonstrated a significant increase of relapse-free survival, the obtained differences in the frequency of postoperative complications and R0 resections after a short course of neoadjuvant chemotherapy provide the rationale to use the developed regimen as one of the standard approaches to the treatment of patients with colon cancer.

Detailed study results:

Seymour TM et al. FOxTROT: an international randomized controlled trial in 1052 patients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer. https://meetinglibrary.asco.org/record/171160/abstract.

ENZALUTAMIDE IMPROVES OVERALL SURVIVAL IN PATIENTS WITH METASTATIC HORMONE-SENSITIVE PROSTATE CANCER: RESULTS OF THE PHASE III ENZAMET TRIAL

Aim of the study: to evaluate the efficacy of adding enzalutamide to the standard-of-care therapy for metastatic hormone-sensitive prostate.

Study design: randomized phase III trial. Patients were randomized at the 1:1 ratio to receive enzalutamide 160 mg QD or standard nonsteroidal anti-androgen (bicalutamide, flutamide, or nilutamide). All patients received androgen-deprivation treatment.

Results: 1125 patients were randomized; patients’ characteristics were well balanced between the arms. At 3 years, overall survival was 79% in the enzalutamide arm vs. 72% in the control arm (HR 0,66; p = 0,002).

Why it is important: another trial has demonstrated that early administration of the most effective drugs for prostate cancer prolongs patients’ lifespan.

Detailed study results:

Sweeney C et al. Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial. https://meetinglibrary.asco.org/record/174531/abstract.

---