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Dr. Banerjee: 
Treatment options for advanced solid tumors remain limited. Why is that, and how are clinical researchers navigating those challenges?  

This is CME on ReachMD, and I am Professor Susana Banerjee. 

So historically, treatment options for advanced solid tumors such as gynecological cancers, biliary tract, pancreatic, and bladder cancer has been limited. Limited in terms of options that yield meaningful efficacy, and then also taking into consideration the toxicities of treatments, the impact on quality of life for our patients, and the life expectancy that's gained with traditional treatments in these malignancies. So if we take gynecological malignancies, for example, up until recently for endometrial cancer and cervical cancer, the treatment has been cytotoxic chemotherapy such as carboplatin and paclitaxel. And then for recurrent disease, treatment options which are effective are very limited, again, to chemotherapy. 

More recently, things have changed with the development of immunotherapy, but there is a need for more treatments. So what's been limiting for our current treatments, our traditional treatments? Well, for cytotoxic chemotherapy agents, it's really about managing those toxicities and the ability to continue treatments for as long as possible as long as patients are benefiting, balancing the toxicities, which have been limiting.  

So it's very attractive to have different options, for example, targeting the delivery of cytotoxic agents with the aim of targeting the tumor cell and then limiting the off-target side effects so that the toxicities may well be more acceptable or different to traditional cytotoxic therapies. It's also important that such an approach may be able to be biomarker driven according to the targeted therapy that we are using for new drug classes, such as antibody-drug conjugates [ADCs]. These hold that promise of limiting toxicities by targeting delivery to tumor cells, but they may well have other effects, such as immunomodulatory effects, which could be beneficial in terms of attacking the tumor, surrounding tumor cells that may harbor the target itself, but also limiting toxicities.  

So advances in solid tumors, the main progress in recent years has been immunotherapy, immune checkpoint inhibitors, for example, in endometrial cancer. This has transformed the care in MMR-deficient endometrial cancer in recurrent disease and now in the first-line setting, and also cervical cancer, looking at immune checkpoint inhibition, the first-line setting in recurrent disease.  

Antibody-drug conjugates have entered this arena, and I think the most promising right now is the HER2-directed ADCs. But in ovarian cancer we have folate receptor-targeted ADC mirvetuximab, and in cervical cancer, tisotumab vedotin targeting tissue factor. Antibody-drug conjugates targeting HER2 have profoundly transformed the treatment landscape for breast cancer. And for HER2-expressing tumors without approved HER2-targeted treatments, and that includes gynecological malignancies, there remains this unmet need for more effective therapies, particularly for patients with recurrent disease who are refractory to conventional therapy that's available in practice. So HER2-directed ADCs are set to change management for these cancers, and it's a new era for precision medicine across other solid tumors. I do believe the future looks really promising, integrating HER2-positive-targeted therapy and ADCs, in general, for HER2-positive solid tumors. It's really important welearn how to assess HER2, the expression across different tumor types. Different levels of HER2 expression may yield different amounts of efficacy in different tumor types, and it's also important, hand in hand, to manage toxicities.  

So please tune in to hear more about how new HER2-targeted therapies are being used to treat solid tumors.  

This has been CME on ReachMD. 

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