ASCO Recap: Leaning in at the Plate, Swinging for the Fences

Everyone loves a grand slam: the crack of the bat, the arc of the ball as it sails over the fence, a tip of the batter’s cap, a triumphal trot around as the bases empty out, but really, it’s the lesser efforts that made it all possible—a double, a single, a walk—it’s the incremental gains that win the game. It’s called Small Ball.

This year’s ASCO, absent the heavy hitters, was all about the small ball and the following is a summary of some of the more interesting players that made it on base:

First Base

NBTXR3 - Manufactured by Nanobiotix, of Paris, France, NBTXR3 is a nanoparticle formulation of hafnium oxide crystals. Hafnium is a heavy metal normally used in filaments and electrodes, and, because of its energy absorbing properties, control rods in nuclear power plants. Nanobiotix has repurposed hafnium to enhance radiation therapy for cancer treatment.

“The key property of the particles is their ability to absorb radiation,” said Bernd Muehlenweg, head of business development at Nanobiotix, presenting the results of a phase I, proof of concept at ASCO. When injected in to a tumor, the presence of NBTXR3 facilitates a nine-fold increase in the radiation delivered.

The study looked at the use of NBTXR3 in conjunction with radiotherapy (RTX) in patients with soft tissue sarcoma (N=17). “At diagnosis, 60% of these patients are unresectable,” explained Muehlenweg, therefore, tumor(s) must be debulked prior to surgery. Unfortunately, conventional RTX is often suboptimal, leaving the surgeon to choose between removing too much healthy tissue to get a clean margin, or not enough tissue, thereby risking cancer recurrence.

Using hafnium nanoparticles to enhance RTX, results of this pilot study showed that 100% of patients were able to go on to successful resection. “The data seen here in soft tissue sarcoma is unprecedented,” said Muehlenweg.

Second base

Lurbinectedin - Manufactured by Zeltia, this drug started out life at the bottom of the ocean as a molecular component of a sea squirt. Many years of development, thousands of squirts, and the synthesis of a few chemical analogs later, lurbinectedin was compared with the standard-of-care, topotecan, in a phase II study of platinum resistant, advanced ovarian cancer patients (N=81).

The results of this investigation, presented by Andres Poveda, MD, of the Fundacion Instituto Valenciano de Oncologia in Spain, demonstrated an overall response rate of 54% for lurbinectedin vs. roughly 15% for topotecan. More importantly, progression-free survival was 5.7 months vs. 1.7 months, favoring the contribution of the squirt, and further, the overall survival for topotecan was 8.3 months, while at the time of ASCO reporting, overall survival for lurbinectedin had yet to be reached.

“The response rate was especially impressive in patients with platinum resistance,” said Dr. Poveda.

A phase III trial with lurbinectedin is already underway, and Zeltia divers are continuously undersea, looking for the next potential blockbuster natural compound.

Third base

Ramucirumab - This monoclonal antibody, manufactured by Eli Lily, targets the vascular endothelial growth factor receptor (VEGFR). Targeting the VEGF receptor interferes with tumor-based signaling intended to trigger angiogenesis, thereby blocking the formation of the new blood vessels required for sustained tumor growth.

Put to the test in REVEL, a phase III investigation, ramucirumab plus the standard-of-care, docetaxel, was compared to docetaxel alone as second-line treatment in a cohort of individuals with advanced non-small cell lung cancer (N=1,253).

The endpoint in this study was overall survival; typical survival in this setting being 7-9 months.

Results of treatment with the addition of ramucirumab showed that overall survival was extended to 10.5 months, versus 9.1 months for docetaxel alone (p=0.023).

“This is the first treatment to show a significant survival advantage over chemotherapy alone in second-line, non-small cell lung cancer,” said Gregory Masters, MD, of the ASCO communications committee. “It’s nice to see incremental progress in this disease. It may seem small—but it’s cumulative—so we’re excited to have another agent that shows activity, especially in this very difficult to treat patient population.”

Homerun

Ibrutinib - Pharmacyclics, in collaboration with Johnson & Johnson, has developed this first-in-class, once-daily oral formulation of a Bruton’s tyrosine kinase inhibitor, which was approved by the FDA in February 2014 for use in chronic lymphoid leukemia (CLL), the most common form of adult leukemia.

The standard-of-care in CLL is chemotherapy followed by rituximab. However, elderly patients, which represent the largest demographic diagnosed with CLL, often cannot tolerate this regimen. The only treatment option for such patients is the anti-CD20 drug, ofatumumab, which is easier to take, but much less effective than chemotherapy.

To address this unmet medical need, ibrutinib was compared to ofatumumab in a cohort of elderly CLL patients (N=391). 

The results were striking. “The progression-free survival at six months was 88%,” said study presenter, John Byrd, MD, professor of medicine at Ohio State University. This rate translates into a reduction in expected deaths of an astonishing 78%.

“This is a very important, practice changing study,” concluded Olatoyosi Odenike, MD, an ASCO spokesperson. “We now have compelling evidence that an oral therapy provides significant efficacy with a high degree of tolerability in patients with treatment refractory CLL.”

Practice changing indeed.

Play ball!