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Dr. Arbour:
Hello, this is CE on ReachMD, and I'm Dr. Kathryn Arbour, and I'm pleased today to be joined by Dr. Eileen O'Reilly.

Dr. O'Reilly, in this episode, we're going to touch on the unmet needs in lung cancer and pancreas cancer. And I’m wondering if you could start by reviewing where we are now in the treatment of pancreas cancer. What are the current unmet needs and need for additional treatment options for patients?

Dr. O’Reilly:
Yeah, thank you. I think this really sets the scene for what the future is holding. So pancreas cancer is a disease in need, right, of new therapies. Traditionally, we treat every stage of this disease with chemotherapy, and chemotherapy has had an impact in terms of ability to shrink cancer, control disease, and extend life with multiple randomness trials in the first- and second-line setting and also in the locally advanced disease setting and in the adjuvant setting that support the value. But I think the field and the community and, most of all, our patients would agree that we need new therapies and we need better therapies. And we've known forever, right, that pancreas cancer is the disease of RAS and recently advent of potential opportunities for effective targeting. And I know we'll come to this in later episodes, but just I think it's clear we have much to do in this disease and the time is ripe for change.

Dr. Arbour:
I think for lung cancer, it's really been an evolving field in terms of how we think about first-line therapy and what our options are really limited in the second-line setting and beyond. So for lung cancer, for patients with KRAS-mutant lung cancer or really no driver oncogene, our standard is really platinum doublet chemotherapy in combination with immunotherapy or given sequentially, so immunotherapy followed by chemotherapy. But beyond those two categories of treatment, then we're left with second-line chemotherapy options, and those are limited in terms of their effectiveness and really limited in terms of the side effects and the quality of life they really deliver for patients.

So our standard treatment when platinum doublet chemotherapy and immunotherapy have either not worked initially for patients or whose cancers have progressed despite these therapies after an initial response, we move on to the chemotherapy docetaxel in this setting.

And docetaxel has been around a long time. It's really our backbone for second-line therapy, but it certainly has its limitations. Response rates are low, typically of the 10% to 15% range across clinical trials. And even when the treatment is effective, responses are very short-lived with a short progression-free survival, and then that translates to a shorter overall survival for patients in that setting. So it's certainly something that we use, but it's not preferred by physicians, and we are constantly in search of how can we replace this as a second-line therapy, as an option.

For patients with lung cancer, it drives substantial toxicities as well, neuropathies, cytopenias, and kind of limitations on quality of life associated with that treatment decisions. So for patients with previously treated non-small cell lung cancer, it is a significant unmet need, especially in the second-line therapy setting for those patients who are no longer benefiting from our initial treatments.

I'm curious. In that setting, especially after initial treatments for pancreas cancer, what are the challenges you see in that setting, Dr. O'Reilly?

Dr. O’Reilly:
Yeah, thank you so much. And I think many parallels again in these two diseases and in the frontline, we expect to see response rates of 30%, maybe 40% progression-free survival of 6, 7, 8 months, depending on the regimen, and 10 to 12 months in terms of overall survival medians. In the second line, those benchmarks are substantially shorter, and median PFS is of the order of a couple of months. And if we look at multiple trials, multiple different largely cytotoxic agents, but many cytotoxic plus investigational therapies that haven't worked out, we'll see benchmarks for around 6 months in median overall survival in a second-line setting. So, again, large unmet need and opportunity for new treatments and similar worries and concerns in terms of fatigue, neuropathy, myelosuppression, infection, and the disease-specific morbidity of pancreas cancer with oftentimes pain, weakness, anorexia, guts, and other considerations.

So I think overall, in both diseases, new therapies warranted.

Dr. Arbour:
Absolutely. And so I think that's an important point to kind of think about as we think about novel therapies in this episode and look forward to future discussions. So thank you so much, and we'll see you next time.

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