Promising Data in CRC and Cholangiocarcinoma, European Approval in Myeloma, and More

Today-

Promising findings in colorectal cancer and cholangiocarcinoma, disappointing data in triple-negative breast cancer, and a European approval in multiple myeloma.

Welcome to OncLive News Network! I’m Gina Columbus.

In the phase III BEACON CRC trial, the triplet regimen of encorafenib, binimetinib, and cetuximab led to a 48% reduction in the risk of death compared with cetuximab and irinotecan-containing regimens in patients with BRAF V600E-mutant metastatic colorectal cancer who previously received up to 2 lines of therapy, meeting both primary endpoints of the study.

Results showed that the triplet therapy was associated with a median overall survival of 9.0 months compared with 5.4 months for those who received cetuximab/irinotecan-containing treatment. The overall response rate, which was assessed by blinded independent central review, was 26.1% and 1.9%, respectively.

Array BioPharma, Inc., the manufacturer of encorafenib and binimetinib, stated that it intends to submit these data for approval in the second half of 2019. The triplet regimen was previously granted a breakthrough therapy designation for this patient population in this setting.

Also, in March 2019, the National Comprehensive Cancer Network updated their Clinical Practice Guidelines in Oncology for Colon and Rectal Cancer to include encorafenib in combination with binimetinib and an anti-EGFR antibody as a category 2A treatment for patients with BRAF V600E-mutant mCRC, following failure of 1 or 2 prior lines of therapy for metastatic disease, based on the safety lead-in BEACON CRC data.

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In cholangiocarcinoma, ivosidenib demonstrated a statistically significant improvement in progression-free survival by independent radiology review compared with placebo in patients with IDH1-mutant previously treated cholangiocarcinoma in the phase III ClarIDHy trial.

Full findings of the study are expected to be presented at the 2019 ESMO Congress. Agios Pharmaceuticals, the developer of the IDH1 inhibitor, stated that it plans to submit a supplemental new drug application for ivosidenib in this patient population by the end of 2019.

Additionally, a next-generation sequencing assay is being provided by Thermo Fisher Scientific to detect IDH1 mutations for all tumor samples as inclusion criteria for study enrollment. The company will also develop and commercialize the companion diagnostic.

In the phase III ClarIDHy trial, patients with previously treated IDH1-mutant cholangiocarcinoma with disease progression after 1 or 2 systemic therapies were randomized to single-agent ivosidenib at 500 mg daily or placebo. Crossover to ivosidenib was permitted at time of progression.

Prior phase I results showed that 4 patients experienced a confirmed partial response, and 41 patients experienced stable disease. Additionally, the median PFS was 3.8 months, and the 6- and 12-month PFS rates were 38.5% and 20.7%, respectively.

In breast cancer, single-agent pembrolizumab did not meet a prespecified endpoint of superior overall survival compared with chemotherapy as a second- or third-line treatment for patients with metastatic triple-negative disease, therefore missing the primary endpoint of the phase III KEYNOTE-119 trial.

Because the primary endpoint was not met, other endpoints were not formally tested as per the study protocol. Moreover, the safety profile of pembrolizumab was consistent with what has been observed with previous studies of the PD-1 inhibitor, and no new safety signals were identified.

In the phase III KEYNOTE-119 trial, investigators randomized 622 patients 1 to 1 with metastatic TNBC to receive pembrolizumab monotherapy compared with single-agent physician’s choice chemotherapy, which included capecitabine, eribulin, gemcitabine, or vinorelbine.

Prior data seen in the phase II KEYNOTE-086 trial had demonstrated clinical activity with pembrolizumab in this patient population. At a median follow-up of 10.9 months results showed that of 170 patients, there was 1 complete response and 7 partial responses with the PD-1 inhibitor. Twenty-seven percent of patients had a decrease in target lesion size from baseline, and progressive disease was reported for 60.6 % of patients.

Full findings of the KEYNOTE-119 trial will be presented at an upcoming medical meeting.

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The European Commission has granted an approval to lenalidomide in combination with bortezomib and dexamethasone for the treatment of adult patients with previously untreated multiple myeloma who are ineligible for stem cell transplant.

The agency also approved pomalidomide in combination with bortezomib and dexamethasone for the treatment of adult patients with myeloma who have received 1 or more prior treatment regimen that included lenalidomide.

The approval for the lenalidomide triplet is based on results from the phase III SWOG S0777 study, in which the regimen demonstrated a 12-month improvement in progression-free survival and overall survival versus lenalidomide/dexamethasone alone as a frontline therapy for patients with myeloma without an immediate intent to undergo autologous stem cell transplant.

Results also showed that the median PFS was 42 months with RVd versus 30 months with Rd alone, and the median OS was 89 months and 67 months with RVd and Rd, respectively. The overall response rate was 82% with the triplet regimen compared with 72% with lenalidomide/dexamethasone; this included complete response rates of 16% and 8%, respectively.

For the pomalidomide-based regimen, the approval was based on results of the phase III OPTIMISMM trial, in which the pomalidomide-based regimen led to a significant improvement in PFS compared with bortezomib and dexamethasone alone.

At a median follow-up of 16 months, data showed that the median PFS with PVd was 11.2 months compared with 7.1 months in the Vd arm, which led to a 39% reduction in the risk of disease progression or death.

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This week, we sat down with Ursula Matulonis, of Dana-Farber Cancer Institute, to discuss recommended approaches to treating patients with ovarian cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.