Experts Explain Their Top Five ASCO Abstracts

GASTROINTESTINAL CANCERS

Robert J. Mayer, MD

Dana-Farber Cancer Institute

REGATTA: Gastrectomy plus chemotherapy versus chemotherapy alone in advanced gastric cancer with a single noncurable factor. Abstract 200.

This relatively small but convincing clinical trial conducted in South Korea and Japan documents the futility of gastric surgery following the use of systemic chemotherapy in patients with metastatic stomach cancer.

KEYNOTE-012: Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with pembrolizumab. Abstract 4001.

This small phase II trial in patients with advanced gastric cancer whose tumors expressed PD-L1 demonstrated, with acceptable toxicity, a 22% response rate following treatment with the anti-PD-1 monoclonal antibody pembrolizumab.

Comprehensive genomic profiling of biliary tract cancers to reveal tumor- specific differences and frequency of clinically relevant genomic alterations. Abstract 4009.

This study reports genomic profiling data on DNA extracted from tissue from 412 intrahepatic cholangiocarcinomas, 57 extrahepatic cholangiocarcinomas, and 85 gall bladder carcinomas, showing significant molecular distinctions among the three subtypes of biliary tract cancers, and suggesting that these subtype-specific genetic patterns should be used as the basis for future clinical biliary tract cancer investigations.

PD-1 blockade in tumors with mismatch repair deficiency. Abstract LBA100.

This provocative phase II trial compared clinical activity of the anti-PD-1 antibody pembrolizumab in 13 patients with mismatch repair-deficient colorectal cancers, 25 patients with mismatch repair-proficient colorectal cancers, and 10 patients with mismatch repair-deficient cancers of types other than colorectal, showing a remarkably high likelihood of clinical response in the mismatch repair-deficient patients with no benefit whatsoever in the mismatch-proficient patients.

CALGB/SWOG 80405: Vitamin D status and survival of metastatic colorectal cancer patients. Abstract 3503.

This study measured plasma vitamin D levels in 1043 patients with metastatic colorectal cancer who were part of a large randomized trial in which no outcome difference was evident among the various treatment options, and showed a prolongation in survival in association with higher plasma levels of vitamin D, providing more evidence of the potential for vitamin D supplementation to improve the outcome in colorectal cancer patients.

BREAST CANCER

Joyce A. O’Shaughnessy, MD

Texas Oncology-Baylor Charles A. Sammons Cancer Center

PALOMA-3: A phase III trial of fulvestrant with or without palbociclib in women with hormone receptor—positive, HER2-negative metastatic breast cancer. Abstract LBA502.

Fulvestrant plus palbociclib is substantially superior to fulvestrant alone in aromatase inhibitor (AI)-pretreated patients. This is a new standard of care for patients who disease recurs/progresses on AI therapy.

Results from a phase II study of enzalutamide in androgen receptor (AR)— positive triple-negative breast cancer (TNBC). Abstract 1003.

Promising results showing benefit from AR inhibition in patients with metastatic TNBC with gene expression profile showing AR-dependent growth/survival. New therapeutic strategy for patients with metastatic AR-positive TNBC.

BEACON: Phase III etirinotecan vs chenmotherpy of physician choice in patients with metastatic breast cancer previously treated with anthracycline, taxane, and capecitabine. Abstract 1001.

Etirinotecan showed improvement in overall survival (OS) of borderline significance and significant improvement in OS in patients with liver metastases or brain metastases. This would be an excellent option to have to treat heavily pretreated patients with liver and/or brain metastases (ER-positive, HER2-negative, or triple-negative).

GeparSixto: Prediction of pathological complete response by homologous recombination deficiency (HRD) in patients with TNBC.

Trial update shows that HRD may predict for benefit from adjuvant carboplatin added to anthracycline/taxane chemotherapy. Awaiting results of HRD evaluation and benefit from adjuvant carboplatin in CALGB 40603.

MARIANNE: Phase III study of trastuzumab emtansine (T-DM1) with or without pertuzumab vs trastuzumab plus a taxane in locally advanced HER2-positive breast cancer. Abstract 507.

MARIANNE trial shows pertuzumab does not add to benefit from T-DM1 as first-line HER2-positive metastatic breast cancer. Because pertuzumab substantially improves OS when combined with taxane/trastuzumab, in my mind this triplet remains the first-line standard of care.

GYNECOLOGIC MALIGNANCIES

Maurie Markman, MD

Cancer Treatment Centers of America

MITO END-2: Randomized phase II trial of carboplatin/paclitaxel compared with carboplatin/paclitaxel/bevacizumab in advanced endometrial cancer. Abstract 5502.

This trial demonstrated that the addition of bevacizumab to carboplatin/ paclitaxel improves progression-free survival (PFS) in stage III/IV or recurrent endometrial cancer.

Interim phase Ib study results: Antitumor activity and safety of pembrolizumab in patients with PD-L1—positive advanced ovarian cancer. Abstract 5510.

This single-arm trial revealed objective activity with pembrolizumab in ovarian cancer, with a response rate of 11.5%.

Wee1 inhibitor: Phase II study with AZD1775 plus carboplatin in patients with TP53-mutated ovarian cancer refractory or resistant (<3 months) to standard first-line therapy. Abstract 2507.

Single-arm trial of the Wee1 inhibitor AZD1775 revealed objective activity in 9 of 22 patients (41%) in platinum-refractory disease recurrent ≤3 months after last platinum therapy.

ARIEL2: A phase II trial to prospectively identify patients with ovarian cancer likely to respond to rucaparib using tumor genetic analysis. Abstract 5508.

This study revealed that the PARP inhibitor rucaparib demonstrated higher PFS rates among patients with BRCA mutations and BRCA-like wild-type ovarian cancer compared with biomarker-negative tumors. The median PFS for mutation carriers was not reached after 9.4 months, compared with 7.1 months for patients with BRCA-like tumors and 3.7 months for participants who were biomarker negative.

TRINOVA-1: Impact of trebananib plus weekly paclitaxel on overall survival (OS) in patients with recurrent ovarian cancer and ascites. Abstract 5503.

A “negative” OS outcome for trebananib in a phase III trial, but in the subset of patients with ascites there appeared to be an OS benefit. This needs to be confirmed in a phase III study.

OncLive invited several experts to choose five practice-changing or noteworthy abstracts in their field from the 2015 ASCO Annual Meeting. Here are their selections, with accompanying commentary. Full abstracts are available at http://meetinglibrary.asco.org.