Preview of ASCO 2017: Top Expert-Selected Studies

Preview of ASCO 2017: Top Expert-Selected Studies

At ASCO 2017, important results from many clinical trials are being reported. Below, expert faculty members have highlighted some of their most anticipated studies. Data from these abstracts will soon be available as downloadable slidesets and as a part of CME-certified online activities where experts will discuss the clinical implications of the data after the ASCO annual meeting.

Lung Cancer—Heather Wakelee, MD
For the upcoming ASCO Annual Meeting, here a few abstracts with new findings that I anticipate will be important for clinicians who treat patients with advanced lung cancer.

• The first study selected is a late-breaking abstract that may help to define whether alectinib should be the new standard of care for first-line therapy in patients with ALK-positive advanced NSCLC. The global phase III ALEX trial randomized 303 patients with newly diagnosed ALK-positive disease to receive either alectinib or crizotinib as first-line therapy. 
• In the first-line NSCLC setting, pembrolizumab was approved as a single agent in October 2016 and is now approved in combination with carboplatin and pemetrexed. At ASCO 2017, updated data from the KEYNOTE-024 trial with extended follow-up will be presented showing durable OS benefit and prolonged PFS after 2 lines of therapy.
• An expanding role of immunotherapy for advanced thoracic malignancies other than NSCLC seems to be supported by promising data from the phase I/II CheckMate 032 trial of nivolumab alone or in combination with ipilimumab for patients with advanced solid tumors including small-cell lung cancer.

For additional expert guidance in making decisions for your patients with advanced lung cancer, please use CCO’s Interactive Decision Support Tool for NSCLC at clinicaloptions.com/lungtool and our Interactive Algorithm for managing immune-related adverse events at clinicaloptions.com/immuneAEtool.

Breast Cancer—Sara Hurvitz, MD, FACP
At ASCO 2017, I am quite interested to see data from the phase III APHINITY trial, which is evaluating the use of adjuvant pertuzumab in combination with trastuzumab/chemotherapy. A press release indicates that the study is positive for its primary endpoint of invasive disease-free survival. As such, this will be the first study to show invasive disease-free survival benefit with the use of dual HER2-targeted therapy in the curative setting. I am also excited to see the MONARCH-2 data, which will be the first phase III trial reporting the activity of abemaciclib in combination with fulvestrant for treatment of hormone receptor–positive metastatic breast cancer. Abemaciclib is the only CDK4/6 inhibitor to be given continuously and to have demonstrated single-agent activity. Its toxicity profile appears to differ from that of ribociclib and palbociclib, with more gastrointestinal adverse events but less neutropenia. It will be interesting to evaluate its efficacy and tolerability profile in the context of this large randomized trial. The results of the phase III OlympiAD trial of olaparib monotherapy vs chemotherapy in HER2-negative metastatic breast cancer and a germline BRCA mutation should also be interesting.

Finally, I am eagerly anticipating the results of numerous clinical trials being presented that are comparing anthracycline-based therapy to nonanthracycline-based regimens for the treatment of early-stage disease, including the phase III PlanB and TRAIN-2 trials.

Hematologic Malignancies— Farhad Ravandi, MD
At this year’s ASCO annual meeting, numerous interesting and potentially practice-changing studies in hematologic malignancies are being reported. In ALL, I am most excited to see the CD19-directed 19-28z CAR T-cell therapy story continue to unfold, with progress being made toward identifying which patients with relapsed B-ALL will optimally benefit from this cutting-edge therapy. For our patients with relapsed/refractory AML, promising data on the mIDH2 inhibitor enasidenib in mutant-IDH2 relapsed/refractory AML and the FLT3/AXL inhibitor gilteritinib in FLT3-mutant relapsed/refractory AML forecasts potential new treatment options on the horizon for these hard-to-treat patient populations. My colleague Sagar Lonial, MD, highlights 2 of the most clinically relevant studies in multiple myeloma reporting at ASCO 2017: phase III results from a study of denosumab vs zoledronic acid for the treatment of myeloma bone disease and phase IIa results from a study of bortezomib, lenalidomide, dexamethasone, and elotuzumab in ASCT-eligible patients newly diagnosed with multiple myeloma. Finally, a suite of phase III studies in lymphoma and CLL reporting at ASCO 2017 piqued the interest of my colleague, John M. Burke, MD, including the 5-year follow-up results of the BRIGHT study on first-line BR vs R-CHOP or R-CVP in patients with indolent NHL or MC, the results of the planned interim analysis of the OPTIMAL>60 study on radiotherapy to bulky sites after immunochemotherapy in patients with DLBCL, and the potentially practice-changing results of the phase III GENUINE study of ublituximab and ibrutinib for previously treated, high-risk CLL (with no previous ibrutinib exposure).

Gastrointestinal Cancer—Alan P. Venook, MD
The virtue of studies of adjuvant therapy is that the results inform us of how to cure more patients. The problem is that these studies take many years to mature and the field may have moved on by the time the results are in. At ASCO 2017, we will see the data from adjuvant studies in colon and biliary cancers that remain relevant. The plenary session will feature a presentation of the IDEA collaboration, which is a pooled analysis of 6 international trials in stage III colon cancer aimed at determining if 6 cycles of oxaliplatin-based chemotherapy is as good as the standard 12 cycles. Meanwhile, we will also see the results of the BILCAP trial from Europe asking if capecitabine is better than no treatment for patients with resected biliary cancers. Also, on the heels of its newly approved pan-tumor indication in MSI-H/dMMR solid tumors, we will see data from 2 cohorts of the KEYNOTE-059 study evaluating pembrolizumab in patients with treatment-naive and previously treated advanced gastric/GEJ cancer.

Genitourinary Cancer—Elizabeth R. Plimack, MD, MS
There are several practice-changing abstracts in the GU Nonprostate Track at ASCO this year. We will see an update of the KEYNOTE-045 data. This is the first randomized trial showing superiority of a new therapy (pembrolizumab) over chemotherapy in postplatinum urothelial cancer. We will also see an update on the KEYNOTE-052 study of pembrolizumab in cisplatin-ineligible first-line treatment of urothelial cancer. Although not randomized, we will learn how the response rate and landmark survival have evolved and how well the biomarker performs with longer follow-up. I am particularly interested in 2 novel agents reporting results from phase I expansion trials: the antibody–drug conjugate enfortumab vedotin (AGS 22CE) in bladder cancer and IDO inhibitor epacadostat combined with pembrolizumab in both RCC and urothelial carcinoma cancer. In the kidney cancer space, 2 groups will report their experience using sunitinib on an adjusted dose/schedule, and the negative results of the PROTECT adjuvant trial of pazopanib vs placebo will be reported so we can parse the details of that trial relative to the previous reports from ASSURE and S-TRAC. For those looking to kick off the meeting with a bang, there will be an excellent clinical science symposium on Friday on genetics and genomics in GU cancer with new data emerging from some novel investigations—“Expanding the Actionable Landscape: Bladder Cancer Genomics.”

Melanoma—Jeffrey S. Weber, MD, PhD
Remarkable progress in the development of new systemic therapies for the treatment of metastatic and high-risk resected melanoma has been achieved in recent years with more advances coming this year at the ASCO annual meeting in Chicago. First, we will hear about long-term outcome data from the phase III KEYNOTE-006 study examining whether the superior PFS and OS with pembrolizumab vs ipilimumab in ipilimumab-naive advanced melanoma patients is durable. In another important study, the initial efficacy results of the prospective phase II CheckMate 204 study will be reported, in which patients with brain metastases from melanoma, a major cause of death in this disease, were treated with nivolumab plus ipilimumab. Finally, we will also hear about data on cutting edge combination strategies in advanced melanoma, including primary results from the randomized, open-label phase II study evaluating the combination of T-VEC with ipilimumab in unresected stage IIIB-IV melanoma and preliminary results from the open-label phase I/II ECHO-204 study evaluating addition of the IDO inhibitor epacadostat to nivolumab in patients with advanced cancer, including melanoma.

Gynecologic Cancers—Ursula Matulonis, MD
This year at ASCO, we will have results from the LION study assessing the efficacy of systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancer with both intra-abdominal complete resection and clinically negative lymph nodes. In addition, follow-up data from SOLO-2 will help us understand both the potential for adverse events as well as the impact on QoL for patients receiving maintenance olaparib. For women with endometrial cancer, the question on the use of chemotherapy with radiotherapy remains. A phase III trial exploring the use of cisplatin and tumor volume–directed irradiation followed by carboplatin/paclitaxel (TC) vs TC for optimally debulked advanced endometrial cancer showed that the combined modality regimen did not increase relapse-free survival vs TC alone for this patient population. Finally, the PORTEC 3 trial investigated the benefit of adjuvant chemotherapy during and after radiotherapy vs pelvic radiotherapy alone for women with high-risk endometrial cancer singles out patients (those with stage III disease) who may benefit from the addition of adjuvant chemotherapy to radiotherapy.