Antibody-Drug Conjugates in NSCLC: Update on TROPION-PanTumor01 Data - Episode 5

Future Outlook

Melissa Suk Heist, MD, MPH, and Solange Peters, MD, PhD, reflect on treatments being developed in the non-small cell lung cancer space that they are excited for and provide some key takeaways and advice for colleagues.

Rebecca Suk Heist, MD, MPH: How would this data change practice? In the current setting, Dato-DXd (datopotamab deruxtecan) is only available in clinical trials. It is worthwhile to enroll patients in clinical trials of this drug because of the signals of activity that we’ve seen. With the data coming out of World Conference For Lung Cancer and ESMO [European Society for Medical Oncology], there is a lot of interest in using this drug in patients with lung cancer. For patients who have progressed on first-line treatments, it’s worthwhile to think about enrolling with clinical trials of ADCs [antibody-drug conjugates] such as this to see if we can improve on patients’ outcomes and help benefit them.

There’s an explosion of new treatments for non–small cell lung cancer. We’ve seen in the past year new approvals for KRAS-G12C target therapies, there are new drugs that can target exon 20. We have drugs that can target HER2. There are an increasing number of drugs that we have at our disposal to use for patients in specific subsets. There’s interest in new mechanisms of action, new immunotherapies, and possibly combinations such as TIGIT and others that are showing some promising activity, and it would be interesting to see what the further clinical trial data shows. There’s advances being made based on the clinical trials and the research that’s ongoing, and not only in the metastatic setting but another area to watch in the future is going to be in the adjuvant and neoadjuvant settings as some of these treatments move up earlier, either before surgery or after surgery or in the setting of chemoradiation. With all of those advances, hopefully, we can start to impact how long people are able to live and survive with their lung cancer.

Solange Peters, MD, PhD: The new treatment paradigms in non–small cell lung cancer have been, until recently, 2 types. First, the development of targeted therapies starting from EGFR. Here I would guess that we got the low hanging fruits, like we say. We have identified the most important drivers; those are the ones which are recurrent from 1 disease type to the other one. Here we can still develop stronger molecules. But there won’t be any major discovery for a large subset of patients. We still have to discover new immunotherapy mechanism. We are at the early days, we were with platinum based chemotherapy. Beyond PD-1, PD-L1 ,and CTLA-4, there are many other pathways which will enlarge the role of immunotherapy front line or second line, including everything about T-cell engineering. It looks impossible today but remember, sequencing was impossible 10 years ago. It’s a new technology about creating an army of T cells against cancer. I believe in the new generations of immunotherapy compounds as well as T-cell engineering in general. Last but not least, in general in the past 2 years, we saw these antibody-drug conjugates. It’s a new engineering process in making them more potent but maybe again, it’s just a beginning. Combination with antibody-drug conjugates will be something which will help us move forward and have a third kind of new weapon in cancer, in lung cancer in particular. And to this end, I’d like to remind you the data presented at ESMO because it’s comparative of the trastuzumab deruxtecan versus a TDM1 in breast cancer. It’s just about drug engineering. It’s the same target but different molecules in terms of how the molecule is constructed. You see this hazard ratio is 17.0 It should be something about how we become powerful and skilled in building new molecules.

Rebecca Suk Heist, MD, MPH: The one point to emphasize is that there is a lot of drug development and promising drug development that’s being done. For patients who have progressed on first- or second-line therapy, enrolling in clinical trials and participating in these trials is something that would be a huge benefit and could be something that could help people. I would encourage people to look for clinical trials and think about them for their patients.

Solange Peters, MD, PhD: If I have to tell the community of doctors treating lung cancer what they should follow today, for me, it’s mainly 2 fields. The first field is the early disease. Before [tyrosine kinase inhibitors] we had adjuvant chemotherapy, improving after surgery 5% survival long term. Now we have 5 neoadjuvant and 5 big adjuvant trials, which will all show some benefit of immunotherapy in early disease, mimicking what we know from cancers such as renal and melanoma. Pay attention to the early disease because the paradigm and the treatment changes will be extremely important in the next 2 to 3 years. The second thing is, we spoke about it before, the unmet need of second line treatment. What will be second line treatment? Antibody-drug conjugates? New immunotherapies? The combination of both? Once you have improved the frontline strategy, and we did in lung cancer, now we need to find a way out as a second line treatment. That’s about following this data which will come with some sitravatinib combination, for example, the new checkpoint inhibitors as well as monoclonal antibodies. We really need to follow what’s being developed in second line because patients like to know what they get front line, but they also want to know that you have good thoughts for the subsequent lines of treatment. And I still believe docetaxel is an old-fashioned kind of opportunity.

This transcript has been edited for clarity.