ASCO Highlights: T-DM1 vs capecitabine and lapatinib in HER2 breast cancer; axitinib in glioblastoma

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Head and Neck Cancer

An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck

Zalutumumab showed reasonable efficacy in platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck patients. Dosing titration based on skin rash evaluation was feasible.

Phase II trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma

Efficacy for the combination of everolimus and erlotinib is reasonable. However, plasma markers of tumor invasion and hypoxia are associated with worse outcomes. Further biomarker analysis may define subsets of patients with significant therapeutic benefit.

Lung Cancer

CA184-156: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab plus etoposide/platinum versus placebo plusetoposide/platinumin patients with newly diagnosed extensive-stage disease small cell lung cancer

The primary endpoint is overall survival; secondary endpoints include overall survival among patients who receive blinded therapy, immune-related and mWHO progression-free survival, best overall response rate, and duration of response. The trial will also characterize safety, and is estimated to enroll 1100 patients.

Randomized phase III trial of gemcitabine and cisplatin versus gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status 2: CAPPA-2 study

Addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of performance status 2 patients with advanced NSCLC.

A phase III comparative study of nivolumab (anti-PD-1; BMS-963558; ONO-4538) versus docetaxel in patients with previously treated advanced/metastatic nonsquamous non-small-cell lung cancer

Central Nervous System Tumors

Use of axitinib, a new-generation tyrosine kinase inhibitor, to decrease glioblastoma growth despite primary resistance to the VEGF-antibody bevacizumab

Axitinib had significant effects on glioblastoma xenografts even with primary resistance to bevacizumab in a so far untreated tumor. There are currently two recruiting phase II trials with axitinib in glioblastoma multiforme. Further comparative studies with bevacizumab should urgently define the potential of this substance in glioblastoma therapy.

Melanoma

Response will be assessed (modified RECIST 1.1) at 9 weeks following treatment initiation and every 6 weeks thereafter until disease progression. The primary objective is to compare the overall survival of nivolumab versus docetaxel treated patients.Next-generation sequencing of genomic and cDNA to identify a high frequency of kinase fusions involving ROS1, ALK, RET, NTRK1, and BRAF in Spitz tumors

Phil Stephens, PhD

Next generation sequencing identified gene fusions in two thirds of Spitz tumors which are likely to be useful as diagnostic markers that may also serve as therapeutic targets for the rare subset of these tumors that metastasize.

Phase II double-blind, randomized study of selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for advanced BRAF-mutant cutaneous or unknown primary melanoma

Mark R. Middleton, PhD, FRCP

Clinical activity was observed in patients with BRAF mutation-positive melanoma treated with selumetinib + dacarbazine, reflected by a nonsignificant improvement in overall survival and a significant benefit in progression-free survival. Tolerability of this combination was generally consistent with the monotherapy safety profiles.

Genitourinary (Nonprostate) Cancer

Record-3: Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma

Robert J. Motzer, MD

Lymphoma

Randomized phase II study of mogamulizumab (KW-0761) plus VCAP-AMP-VECP (mLSG15) versus mLSG15 alone for newly diagnosed aggressive adult T-cell leukemia-lymphoma (ATL)

Tatsuro Jo, MD, PhD

The combination of mogamulizumab with mLSG15 was well tolerated and the study met its primary endpoint. These results suggest that mogamulizumab with mLSG15 is a rational treatment option for newly diagnosed aggressive ATL.

Breast Cancer

Noninferiority of progression-free survival for 1st-line everolimus compared with sunitinib was not achieved in this randomized phase II trial of mRCC patients. The treatment paradigm remains sunitinib→everolimus since the sequence achieved optimal clinical benefit.A randomized phase III study to determine the efficacy of capecitabine in addition to a taxane and bevacizumab as first-line therapy in patients with metastatic breast cancer

TABEA trial failed to show an improvement using the 3 drug regimen taxanes, bevacizumab, capecitabine in high-risk metastatic breast cancer patients.

Etirinotecan pegol target-specific pharmacodynamic biomarkers measured in circulating tumor cells from patients in the phase III BEACON study in patients with metastatic breast cancer

Etirinotecan pegol target-specific pharmacodynamic biomarkers can be reliably measured in circulating tumor cells isolated from patients participating in BEACON. Sample collection and analysis of pre- and post-treatment samples is ongoing.

MERiDiAN: A phase III, randomized, double-blind study of the efficacy, safety, and associated biomarkers of bevacizumab plus paclitaxel compared with paclitaxel plus placebo, as first-line treatment of patients with HER2-negative metastatic breast cancer

The co-primary endpoints are progression-free survival by investigator assessment in the intent-to-treat population, and progression-free survival in the subgroup with high baseline.

A randomized, multicenter, double-blind phase III study of palbociclib (PD-0332991), an oral CDK 4/6 inhibitor, plus letrozole versus placebo plus letrozole for the treatment of postmenopausal women with ER(+), HER2(—) breast cancer who have not received any prior systemic anticancer treatment for advanced disease

More on palbociclib in breast cancer:FDA Grants Breakthrough Therapy Designation for Palbociclib in Breast Cancer

Exposure—efficacy relationship of trastuzumab emtansine (T-DM1) in EMILIA, a phase III study of T-DM1 versus capecitabine and lapatinib in HER2-positive locally advanced or metastatic breast cancer

Gastrointestinal (Colorectal) Cancer

Bevacizumab continuation versus no continuation after first-line chemo-bevacizumab therapy in patients with metastatic colorectal cancer: A randomized phase III noninferiority trial (SAKK 41/06)

Dieter Koeberle, MD

Non-inferiority could not be demonstrated in this trial. The 95% confidence intervals for the TTP HR indicate superiority of bevacizumab continuation after stop of first-line chemotherapy. The median differences in TTP and in time between randomization and start of second-line treatment were of moderate magnitude being less than 6 weeks.

In EMILIA, no clear trends were observed between T-DM1 exposure and progression-free survival, overall survival, or overall response rate, following administration of T-DM1 3.6 mg/kg q3w. However, there was a suggestion of improved overall survival HR by stratified T-DM1 Cmin quartiles, albeit with mostly overlapping 95% CIs. Ongoing trials will further evaluate this potential relationship.

FOLFOXIRI/bevacizumab versus FOLFIRI/bev as first-line treatment in unresectable metastatic colorectal cancer (mCRC) patients: Results of the phase III TRIBE trial by GONO group

Alfredo Falcone, MD

Gynecologic Cancer

Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16)

Andreas Du Bois, MD

More on ovarian cancer:Adoptive T-Cell Therapy and Dendritic Cell Vaccine in Advanced Ovarian Cancer

FOLFOXIRI/bevacizumab compared to FOLFIRI/bevacizumab, significantly increases progression-free survival and response rate. Subgroup analysis suggests a possible interaction between prior adjuvant chemotherapy and progression-free survival benefit. Secondary resection rate does not differ between treatment arms.

Phase II trial of volasertib (BI 6727) versus chemotherapy (CT) in platinum-resistant/refractory ovarian cancer (OC)

Eric Pujade-Lauraine, MD, PhD

Single-agent volasertib showed antitumor activity in ovarian cancer in a range similar to chemotherapy. Adverse events with volasertib were mainly hematologic and manageable, with fewer non-hematologic adverse events than chemotherapy. Exploration of potential predictive biomarkers for volasertib activity is ongoing.

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