Following a dynamic congress like the 2023 ASCO Annual Meeting, it’s only natural to scan headlines in hopes of finding the newest or most unexpected advances that were showcased. And while there are years that yield a new technology or modality that drastically alters the oncology treatment landscape on whole, this year was a reminder that the reality of practice changing data is just as much shaped by tenacious clinicians and scientists who push great drugs and discoveries incrementally forward to work, not just harder, but smarter for patients.
It felt particularly impactful to be reminded of this dedication during a congress with a theme that emphasized the importance of partnering with patients in medicine and clinical research. At the end of the day, the greatest medical and technical innovations may have limited impact if they are not delivered to the right patient, at the right time.
Take, for example, results shown from AstraZeneca’s Duo-O trial of durvalumab in newly diagnosed advanced stage ovarian cancer. Immuno-oncology (IO) assets have struggled to find a foothold in this setting, but the bevacizumab/durvalumab/olaparib maintenance triplet from this trial was found to significantly improve progression-free survival (PFS) over bevacizumab monotherapy.
Notable differences in the Duo-O trial that may begin to explain this initial positive data are the novel combination of PARP inhibitor and immune checkpoint inhibitor (ICI) in this setting, and the exclusion of patients with BRCA mutations. Further work will clarify the clinical impact of these findings and will hopefully see the PFS improvement translate to an overall survival benefit. Nonetheless, at present, the data suggests that the right drug combination in the right patient population may prove key to unlocking the potential of IO options in ovarian cancer.
Several of the presentations at ASCO also underscored the importance of a crucial nuance that is often overlooked – that the right drug may look like the wrong drug when it’s not used in the correct setting. Promising news was presented for TIGITs, another ICI that remains an enticing therapeutic target in oncology despite several clinical misses from high profile trials in lung cancer, including Merk’s vibostalimab and Roche’s tiragolumab. TIGIT blockade likely holds the most promise when combined with other immunotherapies, such as PD-1/PD-L1 inhibitors. Results from the MORPHEUS-liver study showed that addition of tiragolumab to first-line standard of care atezolizumab + bevacizumab resulted in higher overall response rates (ORRs) and longer PFS compared to first-line standard of care alone in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma.
While the addition of tiragolumab to atezolizumab had previously failed to improve PFS in patients with non-small cell lung cancer, the results from the MORPHEUS-liver study suggest the combination may deliver survival advantage in this particular tumor type and patient population, a result that will hopefully be supported by larger phase 3 trials.
IO undoubtedly holds tremendous promise across the oncology landscape, however, data presented from the CONTACT-03 study provided a cautious reminder about the role of timing in untested and unapproved treatment paradigms. CONTACT-03 was the first clinical trial to investigate retreatment with ICIs (in this case, anti-PD-L1s) in any tumor type. In particular, the study enrolled patients with renal cell carcinoma who had previously progressed on PD-1/PD-L1 inhibitors, treating them with either cabozantinib plus the PD-L1 inhibitor atezolizumab, or with cabozantinib monotherapy. In this instance, the trial did not meet its primary endpoint, improved PFS, suggesting that while ICIs have sometimes been used in patients post ICI progression, this does not appear to be the right treatment sequence for this patient population.
Given my experience working on acute myeloid leukemia, and in the hematology space in general, the excitement of seeing novel data from IDH inhibitors ivosidenib and enasidenib revealed during past professional congresses remains top of mind. At ASCO this year, IDH1/2 inhibitors moved into the brain, as Servier presented results from INDIGO, a trial investigating vorasidenib in patients with low-grade glioma, wherein IDH1/2 are often mutated. Vorasidenib is a new IDH1/2 inhibitor that is brain penetrant. INDIGO found that vorasidenib increased PFS by nearly 2.5-fold compared with watchful waiting in patients with gliomas, although significant liver toxicities were present in nearly 10% of patients. If approved, this would provide the first targeted therapy for low-grade glioma, spurred by the therapeutic advancement of rationally designing an IDH1/2 inhibitor that can cross the blood-brain barrier and deliver the right drug to more of the right patients.
When thinking about the complexities of determining the right treatment for the right patient at the right time, a drug that has efficacy across tumor types can be a great boon to clinicians and patients alike. While other tumor/tissue agnostic drugs have been approved in the oncology space, they have more often involved small patient populations defined by a particular molecular or gene expression profile (i.e., NTRK, MSI-H, or dMMR).
Results from AstraZeneca and Daiichi Sankyo’s DESTINY-Pantumor02 trial suggest that Enhertu, an antibody drug conjugate targeting HER-2, may have the ability to target HER-2 expressing tumors regardless of their location in the body. Enhertu, currently approved for breast, lung, and gastric cancers, showed consistent ORRs in cervical, endometrial, ovarian, bladder, and biliary tract cancers. Combining the potential for broad use with the fact that HER-2 testing tends to be widely available, means that these results may help more of the right patients receive the right treatment.
Whether it’s the next big thing that reshapes the landscape of oncology treatment, or a stalwart drug that has shown success in a surprising new setting, our job at MERGE is to bring the science forward in a way that is equally exciting and activating, regardless of the type of innovation. Our medical and brand teams have both broad and deep oncology experience to navigate the challenges and seize the opportunities that come with different marketing scenarios.
For example, introducing a drug like the first approved CAR-T is inherently bolstered by the excitement for a new treatment modality, but it also requires our deep technical knowledge to translate the novelty into a broader understanding of how this modality works and may fit into the treatment paradigm. Conversely, incremental improvements with established drugs may not automatically generate abundant enthusiasm, but by leveraging our extensive knowledge of the oncology space with our cross-functional expertise in omnichannel marketing, we at MERGE find promotional opportunities and avenues that can drive earnest excitement for even modest treatment improvements by connecting the right drug to the right patient at the right time.
Want to connect with a MERGE subject matter to discuss how MERGE can help drive your organization forward in the field of oncology treatment? Visit us here!
BRCA=breast cancer gene; CAR-T= chimeric antigen receptor T-cell therapy; dMMR=deficient mismatch repair; HER-2=human epidermal growth factor receptor 2; IDH=isocitrate dehydrogenase; MSI-H=microsatellite instability; NTRK= neurotrophic tyrosine receptor kinase; PARP=poly-ADP ribose polymerase; PD-1=programmed cell death protein 1; PD-L1= programmed death-ligand 1; TIGIT=T cell immunoreceptor with Ig and ITIM domains.