ASCO 2015: Immuno-Oncology Again Takes Center Stage

Andre Goy, MD

Editor-in-Chief of Oncology & Biotech News

Chairman and Director Chief of Lymphoma Director, Clinical and Translational Cancer Research John Theurer Cancer Center at Hackensack University Medical Center

Although the ASCO annual meeting has become quite a spectacle (32,000 attendees this year!), it has retained its core purpose of providing a unique platform for oncologists to interact and exchange the latest practice-changing research. At this year’s meeting, there was again a great feeling of palpable excitement among oncologists, as we are definitely witnessing the dawn of a new era in cancer care. It is obviously beyond the scope of this column to summarize all of the significant ASCO data, but the few highlights below will help illustrate some of the ongoing dramatic changes in the field.

Likely the most striking research was the confirmation of the impact of checkpoint inhibitors across several cancer subtypes. First, a randomized trial in previously treated, advanced, squamous cell non—small cell lung cancer (NSCLC) comparing nivolumab to chemotherapy (docetaxel), showed significant improvement in both response rate (20% vs 9%) and survival (median overall survival [OS], 9.2 vs 6.0 months and 1-year OS, 42% vs 24%), regardless of PD-L1 expression level. Nivolumab was also shown to improve survival versus docetaxel in pretreated nonsquamous cell NSCLC (median OS, 12.2 vs 9.4 months and 1-year OS, 50.5% vs 39.0%).

In melanoma, data presented at the plenary session showed that the combination of two checkpoints inhibitors—nivolumab (anti—PD-1) and ipilimumab (anti– CTLA-4)—versus either agent alone was impressively superior for both median progression-free survival (11.5 vs 2.9 months for ipilimumab alone) and overall response rate (57% versus 19%). Though the combination was more toxic, this was manageable and the benefit was even seen in PDL1– negative tumors.

Not surprisingly, checkpoint inhibition is being explored as well in other tumors with encouraging data already in head neck cancers and hepatocellular carcinoma, as well as hematological malignancies.

There is no doubt that immunotherapy will play a big role in managing cancer moving forward, either as consolidation or, logically, in combination with chemotherapy, since damages induced by chemotherapy likely render cancer more immunogenic. This relatively new field of immunooncology is rapidly growing, taking advantage of other strategies, as well, from new monoclonal antibodies; to bispecific antibodies, such as blinatumomab and several others in the pipeline (aiming at rescuing the function of T cells or NK cells); and of course, cell therapies with CAR-T cells, the results of which were also updated at the meeting.

CAR T-cells so far have shown amazing activity in a number of B-cell malignancies, particularly in acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma, while other targets are being explored, including in solid tumors and myeloma. An intense race is on for armed modified T-cells, with no fewer than 17 companies currently involved just in CAR type T-cell therapies.

Besides being a core tool in immunotherapy, monoclonal antibodies also serve as drug carriers (ie, antibody-drug conjugates), several of which were updated at ASCO, both in solid tumors (eg, TDM-1 in breast cancer) and lymphoma.

Meanwhile, the field of small molecules or targeted therapies continues to grow, as well. For example, impressive results from the PALOMA-3 trial were presented for the CDK 4/6 inhibitor palbociclib in ER-positive metastatic breast cancer. The study was stopped early after an after interim analysis showed more than double disease control duration in the experimental arm, also providing an opportunity to delay chemotherapy in endocrine resistant metastatic breast cancer. Similarly, the HELIOS trial explored the integration of ibrutinib, the first-in-class BTK inhibitor, with chemotherapy (bendamustine/ rituximab plus ibrutinib or placebo) in relapsed/refractory CLL, showing an impressive 80% reduction in the risk of progression, with no significant added toxicity.

One of the other major focuses of cancer meetings these days is trying to take advantage of high throughput technologies to tackle the extraordinary diversity of cancer to help refine treatment decisions (ie, precision medicine). Besides the rapidly evolving and growing complexity of the numerous technologies and platforms explored, there is a similarly enormous and needed effort to cope with big data to try to create usable practical knowledge. This process should definitely focus on optimization of types and sequences of therapies to improve patient outcomes and hence, reduce costs along the way (reducing variance of management, redundancy, and wrong choices!).

As I introduced Jay Freireich as one of the winners of the third annual Giants of Cancer Care Awards, it seemed very appropriate to be acknowledging him in 2015, as he is the father of modern oncology (first chemotherapy regimen in ALL: VAMP), the discoverer of platelets transfusion, and made several other enduring contributions. Like when Jay started his career, we are definitively entering a new era in oncology, one in which we will not only start to shy away from chemotherapy in some diseases, but some of the emerging novel options—particularly immuno-oncology— will lead to improved outcomes that will not be measured in months, but in years...and hopefully, decades.