An update on some of the recent developments in the field of immuno-oncology.
The competition is getting tougher in the field of immuno-oncology (IO), especially with inhibitors developed to block the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway. Although chimeric antigen receptor T (CAR-T) cells have seen some success, the treatment is still in its early stages of development.
The following are some of the recent developments in IO, a treatment that is revolutionizing cancer care:
1. The going gets tough for nivolumab
Nivolumab (Opdivo), a PD-1 inhibitor developed by Bristol-Myers Squibb, was recently reported to have failed to improve progression-free survival in treatment-naïve patients diagnosed with non-small cell lung cancer (NSCLC), when compared with chemotherapy chosen by the participating physician. The comparator treatments for squamous NSCLC included gemcitabine + cisplatin, gemcitabine + carboplatin, or paclitaxel + carboplatin; and pemetrexed with either cisplatin or carboplatin for non-squamous NSCLC.
Nivolumab is currently approved as first line for inoperable or metastatic melanoma (in combination with ipilimumab for BRaf-positive melanoma), as second line to treat metastatic squamous NSCLC following progression on platinum-based treatments, as second line in renal cell carcinoma that has progressed on antiangiogenic drugs, and as second line in Hodgkin lymphoma that has relapsed following autologous stem cell transplant.
2. Merck gains advantage with pembrolizumab
Nivolumab’s closest competitor, pembrolizumab (Keytruda), meanwhile, performed quite well in the phase 3 KEYNOTE-024 study. Following recommendations by their Data Monitoring Committee, Merck stopped the trial early and has submitted a supplemental Biologics License Application to the FDA for the drug to be used in treatment-naïve patients who have developed PD-L1—overexpressing advanced NSCLC.
Pembrolizumab is currently approved as first-line in advanced melanoma; in platinum-resistant, PD-L1—positive NSCLC; and NSCLC resistant to EGFR or ALK inhibitors.
3. Atezolizumab approved for bladder cancer
In May this year, the FDA approved atezolizumab (Tecentriq), developed by Roche, to treat a common form of bladder cancer. A PD-L1—blocking antibody, atezolizumab is indicated for use as second line in patients with locally advanced or metastatic urothelial carcinoma who have progressed on platinum-based chemotherapy, either as neoadjuvant or adjuvant care. A complementary diagnostic test, Ventana PD-L1, has also been approved for use in tandem with atezolizumab, to enrich for positive responders.
With the growing prevalence of urologic cancers, the drug is expected to do well—Global Business Intelligence Research has expects “blockbuster” status for the drug by 2022, with an estimated revenue generation of $2.5 billion.
4. Juno Therapeutics faces minor setback with ROCKET trial
A leader in the development of the revolutionary CAR-T cell therapy in cancer, Juno’s ROCKET trial—a phase 2 study in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia—was briefly halted by regulators after the company announced the death of 2 patients enrolled in the trial. The study resumed within a week after Juno met with FDA authorities and provided additional data and a plan to alter trial design.
CAR-T cells are genetically reengineered T cells, drawn from the patient’s own body, that are forced to express chimeric antigen receptors on their cell surface to boost their ability to detect and destroy cancer cells. Following expansion in the laboratory, the cells are infused back into the patient to further multiply and attack the cancer.
5. What do payers think?
The opinion is mixed, according to Michael Kolodziej, MD, former national medical director, Oncology Strategies, at Aetna. These innovative treatments are expensive, with the drug cost alone in the $100,000 to $150,000 range. Combination and sequential treatments will further increase the cost of care when using IO agents. “I think there’s a little bit of concern among the payer community about the cost of these combination therapies. There’s also concern about the toxicities of combination therapies. At this point, most health plans would view that as an experimental approach for most patients, and they’re standing back to wait and see what happens,” Kolodziej said in his interview with The American Journal of Managed Care.