Welcome to another week of updates in cancer research news! Last week, we talked a good bit about EHA. Now, we’re out of the weeds of one of the busiest seasons for conferences, and we’re left to ponder what else the year has in store for us.
I will note that ASCO 2018 results continue to be worth considering. If you haven’t seen it already, consider checking out my series called “Mining ASCO 2018’s Gold.”
- Early breast cancer
- More breast cancer
- Brain cancer
- Radiation and immunotherapy combos
- Important targeted therapy developments
- Immunotherapy combinations
- Colorectal cancer
- Liver Cancer
- Prostate Cancer
- Gynecologic tumors
- Head and neck cancers
- Hematologic malignancies
- Lung and thoracic malignancies
Of course, that does’t mean that the news has stopped flowing, either. What happened last week?
The two big pieces of cancer news on June 23 were the initiation of a pair of trials. One dealt with Regeneron’s PD-1 inhibitor called cemiplimab, in combination with a pair of therapeutic vaccines from Inovio. This combo is being studied in glioblastoma, which remains a major unmet need in cancer. While the news isn’t particularly actionable, it is important for the field, since we need more treatment options for this tumor type.
We also heard for the first time in a while from Novartis’s recently acquired company: Advanced Accelerator Applications. These guys, if you recall, developed Lutathera for the treatment of certain kinds of neuroendocrine tumors. Now, they’re just getting started with a phase 1/2 trial targeting castration-resistant prostate cancer.
While not quite as big a deal as glioblastoma, we continue to need better treatment options for patients with advanced prostate cancer, as many of them will eventually expend all available treatment options.
Day’s impact for cancer medicine: Low, since it’s just the start and planning of a few new trials
The only piece of cancer-related news covered on June 24 was a doozy. Bristol-Myers announced that the FDA accepted their supplemental new drug application for the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) in patients with non-small cell lung cancer and no prior treatment.
The catch is that patients have to have a feature called high tumor mutational burden to qualify for this type of therapy. This is measured by taking the patient’s tumor, sequencing part of the “exome” (that is, the part of the genome that is responsible for encoding actual proteins), and figuring out, on average, how much mutation has occurred in the tumor.
Due to the relationship between lung cancer and carcinogen exposure (particularly cigarette smoke), this form of cancer is associated with a typically high level of tumor mutational burden. And Bristol-Myers showed recently that the combo of Opdivo and Yervoy can be better than chemotherapy in patients with high mutational burden.
I, for one, am not certain how the application will go, since we don’t have the techniques for measuring this burden reliably. It is not standardized, and it is not available in most clinical sites at this time. So there is controversy surrounding the use of this tool. I remain hopeful for its use, though, and I expect that this approval will eventually go through.
Day’s impact for cancer medicine: High, a chemotherapy-free combination makes a big difference in first-line lung cancer
The highlight for June 25 was the modification of pembrolizumab’s (Keytruda) and atezolizumab’s (Tecentriq) approvals. Now, patients who are not good candidates for platinum chemotherapy can still receive one of these drugs instead. However, now their tumor has to test positive for PD-L1 using a companion diagnostic.
This isn’t the biggest setback, because it doesn’t apply to any other approval for these drugs. However, it does signify the ongoing confusion about how exactly the PD-L1 test should be applied for patients. The big problem is that we have seen, in many cases, that being PD-L1 “negative” doesn’t mean you won’t respond to therapy.
In fact, tumor mutational burden (discussed above) is shaping up to be one of the important substitutes, once we figure out how best to use it.
But the impact here should be low, because the modification was based specifically on findings from two clinical trials in the first-line setting, which showed no benefit for immune checkpoint inhibitors if patients were PD-L1 negative. This limits the spread of this news by quite a bit.
Day’s impact for cancer medicine: Intermediate, as there is still controversy across oncology surrounding the best use of immune checkpoint inhibitors, and this is just one more skirmish in that war.
The biggest news covered on June 26 was the revelation that Roche’s atezolizumab (Tecentriq), when added to chemotherapy, can significantly improve overall survival in patients with small cell lung cancer. This form of lung cancer represents around 15% of all lung tumors, and it’s a major unmet need.
What’s more, so far the results of immune checkpoint inhibition in this disease have been underwhelming. But if you add a PD-L1 inhibitor to chemotherapy, you can apparently make a meaningful difference in extensive-stage disease. This is a groundbreaking discovery, and it has big implications for continued development of atezolizumab.
On the flipside, however, was Pfizer’s news that their CDK4/6 inhibitor palbociclib (Ibrance) did not end up improving overall survival in patients with advanced breast cancer in the pivotal PALOMA-3 study. This hasn’t had a major impact in the oncology community, though, because it was understood that this would be a tough bar to clear.
Why? Because of crossover. Patients who progressed on the placebo in PALOMA-3 were not barred from participating in other trials or receiving other treatments. So the benefit that they realized from palbociclib could have been masked by the subsequent therapies they received. Also, overall survival was not the main objective of the study.
The more catastrophic bad news I covered related to Erytech Pharma, who announced that they would be terminating their study involving a new version of asparaginase in acute lymphoblastic leukemia. They are now undertaking a much riskier pancreatic cancer study, and the stock has responded accordingly:
I am hoping that their new trial in pancreatic cancer goes well, but for now they would appear to be radioactive.
June 27’s coverage was about something that surprised me greatly. Puma Biotechology, despite the rejection their drug neratinib received earlier this year, has gotten the reversal. Their appeal of the negative opinion has yielded what looks like a near guarantee of approval in the European Union.
If you recall, neratinib is a small molecule tyrosine kinase inhibitor that has been studied in HER2-positive breast cancer. It was approved last summer in the United States as “extended adjuvant” treatment for early-stage disease. Extended adjuvant refers to a drug that is given for some long period of time after surgery. In this case, “long” means one year.
The European Medicines Agency (EMA) did not share the FDA’s assessment of the risk/benefit ratio for neratinib originally, as the drug has long been shown to be associated with high rates of severe diarrhea. Addition of preventative medication using loperamide (Immodium) made a big enough difference that the FDA allowed their application through.
Now, it looks like they’ll get the approval in Europe, after all. And Puma now sits at roughly 20% higher than its recent trend. The big question now is whether they’ll recover to the $90 per share that they fell from on announcement of the CHMP’s negative decision earlier this year?
On June 28, I covered some huge events. In my opinion, the biggest was that AstraZeneca was able to show that their PARP inhibitor olaparib (Lynparza) was able to improve progression-free survival for women with ovarian cancer. This relates specifically to when it is used as “maintenance” therapy following a response to platinum-based chemotherapy. These results, from the phase 3 SOLO-1 trial, are the first validation of PARP inhibitor efficacy in the first-line treatment setting, and I’m absolutely psyched to hear it!
In other news, we saw Pfizer submit a new drug application for their inhibitor of a protein called “smoothened.” The drug is called glasdegib, and it has been studied in acute myeloid leukemia in the BRIGHT 1003 study. This comes as a surprise, since we have heard very little from Pfizer on this drug, save for some top-line phase 2 data at ASH 2016. Given the bit of efficacy we’ve seen, it looks like glasdegib could be making a pretty big difference in AML and MDS. Now we wait until December to see if the FDA agrees!
Finally, the news kept on rolling as Array Biopharma got their approval from the FDA for the combination of encorafenib/cobimetinib in the treatment of BRAF-mutated melanoma. This news, along with their deep clinical pipeline, has triggered questions as to the likelihood that ARRY will be bought out by another company, a topic I covered in some depth recently. Needless to say, this first approval is a watershed moment for Array Biopharma!
Most of the news on June 29 focused on non-oncology indications, leaving just one event to come out of cancer medicine. Actinium announced that they were initiating a trial of their radioactive drug Actimab-A in a new setting of AML treatment.
Specifically, patients who have persistent minimal residual disease following first-line therapy will receive “consolidation” treatment using chemotherapy and Actimab-A. The intent here is to try and achieve total eradication of the tumor cells.
This trial is another move in a growing trend toward targeting minimal residual disease as a clinical endpoint. We saw recently that the European LeukemiaNet came to a consensus on the definition and measurement of minimal residual disease in AML, which helps to legitimize and spread the use of this tool to a wider range of patients. Hopefully, Actinium has on their hands a tool to help clinicians annihilate the tumor cells.
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