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ADC Components: Antibody

There are a couple of really important components that make up ADCs, or antibody drug conjugates, starting with the antibody backbone itself.

The antibodies used for ADCs are generally chimeric or humanized monoclonal IgG antibodies that are used to target something that is specifically expressed on the tumor surface. We will talk today mostly about HER2, TROP-2, and HER3, but this could be any number of targets.

ADC Components: Linker

The second piece is the linker.

The linker is there to connect the payload to the antibody, but what is important to note is we have cleavable linkers, whether that is something like a disulfide bond that is broken or something that is hydrolyzed within the tumor cell, or we could have non-cleavable linkers where the entire molecule, the whole antibody drug conjugate gets internalized to a lysosome, broken down, and then released from there.

So, two different main classes of linkers.

ADC Components: Payload

Finally, we have the payload, which is typically a very toxic chemotherapeutic agent. There are a number of factors within the payload that are important to consider, such as the drug-to-antibody ratio, which is simply how many of these toxins are tethered to an individual antibody, the lipophilicity, which impacts the ability of the drug to permeate into neighboring cells, and then the half-life, which of course could affect our toxicity and efficacy of the drug.

There are multiple different payloads that are being studied around the market today.

ADC Mechanism of Action

Looking more at the mechanism of action, the antibody drug conjugate binds to the target receptor on the cell surface, forming the ADC antigen complex.

After this binding happens, this complex is internalized and targeted for destruction within the tumor cell itself. The ADC is processed within endosomes or lysosomes, which releases that payload so that it could have  that cytotoxic effect, on the target cell of interest.

Increasingly important, though, is this concept of the bystander effect. Once the toxin is released from its antibody, it is able to migrate into neighboring cells. That could be a tumor cell that maybe is not highly expressing that surface receptor, or it could be a normal, healthy cell. Either way, this could have benefits and potential risks as well.

Finally, the antibody component of the ADC, in some cases, will engage with immune effector cells to trigger additional destruction via the ADCC mechanism.

ADC Mechanisms of Toxicity

There are a couple of mechanisms of toxicity that we want to be aware of, starting first with the expression of the target protein on non-cancer cells.

Certainly, the mechanism of the ADC relies on this target being expressed on the tumor cell, but as we know, some of these targets are also on healthy cells. Thinking about HER2 being expressed on the endothelium throughout the body, so the trastuzumab antibody drug conjugates are not only hitting the tumor cells, they are also potentially targeting the epithelium that is expressing HER2.

The location and mechanism of the linker cleaving is something else to be aware of. We want to make sure as much as possible that that linker is cleaved within the tumor cell, but there could be some leakage, to where the toxin is being released, either outside of the tumor cell, or the potential for migration of that toxin into neighboring cells if that toxin is membrane permeable or lipophilic.

If we are having this leakage of the toxin into the bloodstream or into neighboring cell areas, we could be damaging healthy cells in addition to the target.

Considerations for Currently Approved ADCs Targeting HER2, HER3, and TROP-2

Now we will move into some of the currently approved drugs.

HER2: A Key Targetable Biomarker in Cancer

Starting with our anti-HER2 therapies, many of you are probably familiar with HER2 being a transmembrane receptor. It functions by dimerizing with another member of the EGFR or Erb family, which could be HER1 through 4. After dimerization, there is downstream signaling through a few different pathways that ultimately leads to survival, proliferation, and angiogenesis within the tumor cell.

Anti-HER2 therapies have potential for use in a number of different cancers, starting with breast cancer, gastric cancer, and then a number of others as well.

The lining of the GI tract, the skin, the cardiac myocytes all express HER2 also, and that is where some of the toxicities that Danielle will speak about come into play.

Trastuzumab Emtansine: HER2-Targeted ADC

Trastuzumab emtansine was our first ADC in the HER2 space. It is the same trastuzumab backbone that we are well familiar with. Linked to it via a non-cleavable linker is a very potent emtansine derivative and antimicrotubule payload that is tethered to that antibody. The drug-to-antibody ratio is on the lower end, about four toxins per antibody.

T-DM1: 2 FDA-Approved Indications

The FDA-approved indications currently are both in the breast cancer space. In metastatic breast cancer, trastuzumab emtansine is approved on the basis of progression-free survival and overall survival for patients who were previously treated with trastuzumab and a taxane.

About six years later, it was approved in the adjuvant space, again on the basis of impressive disease-free survival and overall survival. Specifically, the drug is approved for patients who have received neoadjuvant treatment and have residual disease after completion of that neoadjuvant therapy, and that is where it has been shown to significantly reduce the risk of recurrence and overall survival.

Trastuzumab Deruxtecan: HER2-Targeted ADC

Moving into trastuzumab deruxtecan, this agent is, that same trastuzumab backbone.

Trastuzumab deruxtecan has a much higher drug-to-antibody ratio of about eight molecules of toxin to one antibody, and that payload specifically is a topoisomerase 1 inhibitor. The linker on this drug is cleavable, which allows for the bystander effect in combination with the fact that the toxin is membrane-permeable. So this is a very potent drug, and as such, it has been approved in many different areas.

T-DXd: 3 FDA-Approved Indications in Breast Cancer

Looking at the breast cancer indications briefly, we know that this drug is approved in metastatic breast cancer that is HER2-positive. That was its first approval.

It has actually moved up in the treatment algorithm to the second-line setting and that again is based on our PFS and overall survival benefits in the HER2-positive space.

The next indication was in HER2-low tumors. So these are tumors that basically did not quite meet the criteria for HER2 positivity. Our HER2-low definition is those who are IHC1+, or 2+, but had a negative FISH ratio. In the DESTINY-Breast04 trial, trastuzumab deruxtecan showed to be very positive for patients with HER2-low disease.

Last but not least, our more recent indication for breast cancer came from the DESTINY‑Breast06 trial that looked at patients who are either HER2-low, as previously defined, or HER2-ultralow. So HER2-ultralow is those with IHC0, but they do have some amount of membrane staining. So this is very, very minimal amounts of HER2 expression, but the drug seems to still be efficacious in that population.

I will add for that HER2-low and HER2-ultralow that patients have to be HR-positive or hormone receptor-positive as well to qualify on the basis of that study.

T-DXd: FDA-Approved Indication in HER2+ Advanced Gastric/GEJ Adenocarcinoma

Moving into our gastric and GE junction carcinoma, the DESTINY-Gastric01 trial found trastuzumab deruxtecan to be beneficial versus physician's choice chemotherapy.

PFS was improved, and overall survival also improved there as well. So that is an indication in the gastric and GI junction space after trastuzumab therapy.

HER2-Positive NSCLC

Non-small cell lung cancer is a little bit unique in that there is an additional qualifier for HER2 positivity that comes into play here. Specifically, about 2-4% of patients with non-small cell lung cancer have a HER2 gene mutation that can be detected on next-gen sequencing, specifically on exon 20. So where trastuzumab deruxtecan has its indication for non-small cell lung cancer is specifically in those patients with a gene mutation –

T-DXd: FDA-Approved Indication in HER2-Mutated mNSCLC

– as was studied in the DESTINY-Lung02 study.

PFS was pretty impressive at about ten months, which led to accelerated approval of trastuzumab deruxtecan for non-small cell lung cancer.

T-DXd: FDA-Approved Indication in Unresectable/Metastatic HER2+ Solid Tumors

Even more recently trastuzumab deruxtecan now has an indication for unresectable metastatic HER2-positive solid tumors across the board.

Data from a couple of different studies that led to this approval, the PanTumor02 trial especially included patients with a number of different tumor types, and then we could add the lung data as well as colorectal data into that, and this led to an accelerated approval across the board for HER2-positive solid tumors who previously received systemic treatment and have no satisfactory alternative treatment option available.

Key Data and Indications for ADCs Targeting TROP-2

Moving on, we will now look at our anti-TROP-2 agents.

TROP-2 as a Therapeutic Target

TROP-2, for a quick overview, is an epithelial adhesion molecule that regulates many different pieces of the cell cycle or the cell lifespan, including regeneration, growth, and transformation.

TROP-2 Overexpression Across Tumor Types

It is overexpressed on many different tumor types. We will specifically talk about breast, since that is where the drug has its indication currently, but you could see potential opportunities in multiple different tumor types as TROP-2 is highly expressed in several different cancers.

Sacituzumab Govitecan: TROP-2‒Targeted ADC

Sacituzumab is an anti-TROP-2 humanized antibody. It has a similar profile to trastuzumab deruxtecan, I would say, in that the drug-to-antibody ratio is about 8:1. This time we have a pH-sensitive, cleavable linker that aids in the release of that toxin within the tumor.

The payload is SN-38, which you might recognize as the active metabolite of irinotecan.

Sacituzumab Govitecan: 2 FDA-Approved Indications

In metastatic triple-negative breast cancer, this is where sacituzumab got its first approval via the ASCENT trial. We saw an improvement in progression-free survival as well as overall survival, and it now has a full FDA approval for patients with metastatic triple-negative breast cancer after two or more lines of prior therapy, one of those being in the metastatic setting.

It later got approved in the hormone receptor-positive breast cancer space, again with metastatic disease who were previously treated, and this has not quite as numerically impressive results as what we see in the triple-negative population, but at last, we do have a full FDA approval for sacituzumab in the HR-positive metastatic space also for breast cancer.

Datopotamab Deruxtecan: Novel TROP-2‒Targeted ADC

More recently, we have datopotamab deruxtecan, which is a newer anti-TROP-2 drug.

We now have a tumor-selective cleavable linker, again, a tetrapeptide-based linker, and its payload is a topoisomerase inhibitor, again, same one that we have seen with trastuzumab deruxtecan. The bystander effect is very important with this agent.

Dato-DXd: FDA-Approved Indication

Dato-DXd is approved based on TROPION-Breast01, which studied patients with HR-positive metastatic breast cancer, and what the results show is an improvement in overall response rate, an improvement in progression-free survival, and thus, we have an FDA approval for Dato-DXd.

There are also some investigation ongoing for non-small cell lung cancer.

Patritumab Deruxtecan (HER3-DXd): Novel HER3-Targeted ADC

And with that, I will turn it over to Danielle to take over on AE identification and management.

ADC AE Identification, Management, and Communication/Care Coordination

Dr. Danielle Roman (Allegheny Health Network): Thanks, Allison. We are going to move on to talking about side effect profiles, how to identify side effects, and also from the management end, how are we going to prevent these as well as manage them if they do occur.

Considerations for AEs Associated With HER2-Targeted ADCs

We are going to start with a discussion of the adverse effects associated with the ADCs that target HER2.

Common (in ≥30%) and Dose-Limiting/AESI Toxicities Associated With T-DM1 and T-DXd

So first a brief discussion of T-DM1. This is the agent we have had on the market for the longest period of time now, so do have pretty significant experience in managing these side effects.

So overall, I would say generally a well-tolerated agent but a couple of toxicities to note, certainly with fatigue, hepatotoxicity some myelosuppression particularly with thrombocytopenia and neuropathy are things to watch for.

Switching gears here, as we talk about trastuzumab deruxtecan, or T-DXd. Alopecia is something to note with this agent that somewhere between 20‑50% of patients will experience at least some thinning of the hair. And then certainly something of note here is interstitial lung disease or pneumonitis is listed at 9-12% of patients.

You again see a low risk of left ventricular ejection fraction decrease. There are also a risk of hepatotoxicity with increased AST and ALT nausea rates are fairly high which we will discuss in a little bit more detail as well. And then with the cytotoxic component we do see some neutropenia as well as thrombocytopenia and again, fatigue is something that we are monitoring very closely.

So in terms of those black box warnings with trastuzumab deruxtecan, ILD and pneumonitis as well as embryo fetal toxicity.

ADC-Related ILD/Pneumonitis

As we move on to specifically some discussion of ILD, this is something that we see with other agents. We can see it with cytotoxic chemotherapy with our taxanes and anthracyclines. We can also see this with targeted therapies, other targets against the anti-HER2. We see this with some of our oral targeted therapies such as our CDK4/6 inhibitors, osimertinib, everolimus, so a number of agents that we are using in oncology can have this toxicity, although, it is certainly one of interest as we talk about trastuzumab deruxtecan.

The interstitium is the space between the alveoli of the lung and the capillaries where oxygen taken to other parts of the body and distributed to organs. We need to have effective exchange of oxygen between the alveoli and the capillaries. Interstitial lung disease is damage to that interstitium, so disruption of alveoli structures and fibrosis that limits that gas exchange.

The mechanism here is not well elucidated.

As a high-level summary here, with sacituzumab govitecan really very limited to no risk of ILD.

If we look at T-DM1 and datopotamab deruxtecan, fairly limited risk. However, particularly when we look at T-DXd, this is where we see the highest risk, up to about 15% seen in some of the breast cancer trials. And I think what is particularly noticeable is that there were some cases of grade 5 or fatal ILD that were seen in many of these clinical trials. And this was despite understanding that the risk was there, and really intense monitoring that was happening in these trials. Fatality rates decreased, but we still continue to see some fatalities on these trials. Certainly, a side effect that is very notable with T-DXd and one that we need to monitor for very closely.

ILD Risk Factors: Pooled Analysis From 9 Phase I/II Trials of T-DXd in Solid Tumors

There was an interesting, pooled analysis that was done of nine phase I and II trials of T-DXd in solid tumors.

What they found in this pooled analysis is that the overall incidence of ILD was about 15%, so significant risk. However, most were grade 1/2, and most of the events occurred within the first year of therapy. So certainly, the risk does carry beyond a year, but recommending intense monitoring in that first year to pick up these cases hopefully early as a low-grade event.

Another important point that came out of this pooled analysis was looking at subgroup analysis. Hoping to identify risk factors that would help us understand the patients that carry the highest risk. What they found here was that these potential risk factors included patients that were younger age, so less than 65; those treated in Japan; those patients with lung comorbidities at baseline; those patients with some degree of renal dysfunction, so moderate-to-severe renal dysfunction as determined by the Cockroft-Gault formula; those patients that were more than four years out from their diagnosis; those with a higher dose, so greater than 6.4 mg/kg dose, which of note is doses that were using more in the gastric space; and as well as those patients with low baseline oxygen levels.

So these were risk factors that can potentially identify higher-risk patients. We do not necessarily have any specific differentiation in terms of screening strategies. However, for patients that have these baseline risk factors or potentially multiple baseline risk factors here, you may want to consider more frequent monitoring and certainly intense patient and caregiver education for people taking care of these patients.

Managing ILD/Pneumonitis With T-DXd

We are next going to talk about our treatment algorithm once we have a patient with ILD. Certainly, early identification being very, very important. This should be a part of our regular patient and caregiver education as we start patients on T-DXd. They should be counseled to immediately report any changes in their breathing, new onset cough, dyspnea, fever, really any new or worsening respiratory symptoms.

Based on this, we should do an assessment. High-resolution CT is the preferred test to confirm a diagnosis of ILD. However, you will rule out any other potential causes of respiratory changes before moving on here. So potentially involving our pulmonary colleagues as well as our infectious disease colleagues here to help just confirm the case of ILD.

For patients with asymptomatic disease this is considered to be grade 1 ILD, and the recommendation is to hold therapy until patients have resolved to a grade 0, or no evidence of ILD. There is also a consideration for corticosteroid treatment here. This is usually a 0.5 mg/kg prednisone dose, or potentially up to 1 mg/kg here For patients that are symptomatic they are diagnosed with a grade 2 or greater symptoms here, and the recommendation is to permanently discontinue the drug.

 These patients should initiate systemic corticosteroid treatment with 1 mg/kg of prednisone or equivalent for at least two weeks of treatment, followed by a taper for at least four weeks. Again, for those symptomatic patients, we are not going to re-challenge.

For those patients with grade 1 or asymptomatic disease that is caught oftentimes on routine monitoring, these patients can resume therapy once we have resolution. If that resolution has occurred at 28 days or less from the onset of ILD, we can restart with the same dose. However, for those patients that it takes longer, so greater than 28 days from onset to resolution, the recommendation is to dose reduce here. And once the drug is dose reduced, it is not recommended to re-escalate. Once patients get to that third dose reduction, it is recommended to permanently discontinue the agent.

I would like to also just mention there is not a specific recommendation in terms of our monitoring, besides we know we want to do a high-resolution CT scan as a monitoring strategy, and that is anywhere from every 6 to every 12 weeks.

Currently, in my practice, we are checking high-resolution CTs every nine weeks, which is around the time we are checking for disease response to therapy.

Detecting and Managing T-DXd–Related Interstitial Lung Disease: The 5 “S” Rules

A brief overview of 5 "S" rules for detecting and managing T-DXd related ILD.

Screening, we discussed, a very important component of treatment. So careful patient selection and making sure that those patients are getting those high-resolution CT scans every 6-12 weeks throughout therapy.

Scan, here being the second "S" we discussed.

Synergy. A team approach to identifying and managing these side effects. This is the patient and caregiver team, this is the oncology care team, including our nurses that are working very closely with these patients in the infusion centers, our clinic teams as well as often pulmonary and ID support.

Our fourth "S", suspending treatment. Stopping the drug immediately if ILD is suspected, and only resuming if a patient has grade 1 disease that has completely resolved.

And then finally, our fifth "S" here, steroids. Remembering that this is an important component. It is a consideration for grade 1 disease. It is often used in my experience in that setting, but certainly a necessary component for any patient that has symptomatic ILD.

Managing Clinically Significant Nausea and Vomiting With T-DXd

Another important consideration with T-DXd is the significant nausea and vomiting risk. This agent is categorized as highly emetogenic by NCCN guidelines, and it is recommended that we premedicate with a 3 to 4 drug regimen here to prevent chemo-induced nausea and vomiting.

So this is generally a steroid, a 5-HT3 receptor antagonist, NK1 receptor antagonist plus or minus olanzapine. And an important note that the side effect may be delayed. We want to make sure that we are covering patients not just on that day 1 of treatment, but also for about the first four days after treatment with prophylactic antiemetics and making sure that they have a take-home antiemetic to use as needed beyond that.

Managing Neutropenia With T-DXd

Another important adverse effect with T-DXd is neutropenia. This is likely an adverse effect that many of you are familiar with managing in many other anti-cancer therapies. However, here educating patients on the potential for neutropenia, it is important to note that this is usually a low-grade, low-risk of febrile neutropenia here. We do want to monitor a CBC with differential before starting treatment, before each dose, so this is every three weeks, and as clinically indicated. The median onset for neutropenia is usually somewhere in the 2-3 day range after starting treatment.

It is recommended to hold the drug if the patient's ANC is less than 1000 or if they have neutropenic fever. Dose reductions are warranted for a patient with grade 4 neutropenia or those patients with grade 3 febrile neutropenia.

Discontinuation of the drug should be considered for patients if they have required multiple dose reductions. So if you get to your third dose reduction, discontinuation is recommended. G‑CSF could be a consideration here for patients that do present with neutropenia, so potentially doing this as secondary prophylaxis and for patients that have a significant history of prior neutropenia complications.

Monitoring Left Ventricular Dysfunction With T-DXd

Left ventricular dysfunction is something that we are familiar with monitoring with other HER2-targeted therapies, and it has been reported at about 2-8% in clinical trials with this agent. However, we do want to monitor LVEF prior to initiation of T-DXd, this is either with an echo or a MUGA scan, and at regular intervals throughout treatment. This is not well-delineated in the prescribing information of the drug. In my clinical practice, we, at least as we initiate the drug, do this every three months. However, occasionally space this out as patients are stable on this drug for long periods of time.

The recommendations for management here are based on that absolute LVEF that is determined on the echo or MUGA scan as well as comparing to previous echo or MUGA scans to look at the absolute decrease from baseline. It is important that if you start with a MUGA, ideally you continue with that versus starting with "echo" continue with an echo so that you are comparing apples to apples here.

If we have a patient with an LVEF of 40‑45% and an absolute decrease from baseline of 10-20%, this is a patient where it is recommended to hold the drug and to reassess the LVEF within three weeks. If the patient has not recovered at baseline, it would be recommended to discontinue. If recovered within 10% from baseline, you can resume. And then for patients that either have an LVEF of less than 40% or an absolute decrease from baseline from greater than 20%, the recommendation is to hold it, and reassess within three weeks. If this is confirmed again, it would be recommended to discontinue the agent.

And then for a patient with a diagnosis of CHF, it is recommended to discontinue T-DXd.

Considerations for AEs Associated With TROP2-Targeted ADCs

We are now going to move on to considerations for adverse effects with our TROP-2-targeted ADCs.

Common (in ≥30%) and Dose-Limiting/AESI Toxicities Associated With Sacituzumab Govitecan vs Dato-DXd

There are a few notable things here with sacituzumab govitecan. A significant risk of fatigue, fairly significant risk of hypersensitivity reactions, that we will briefly mention. Alopecia is a concern in up to 50% of patients. Significant risk of nausea and vomiting. Over half of patients experiencing that. Diarrhea risks that are very high. And a significant risk of neutropenia as well at 64%.

A brief overview of the Dato-DXd. Again, alopecia is an adverse effect in up to 40% of patients. In Dato-DXd we see a risk of ocular events and stomatitis, low risk of ILD. Nausea is something of concern here. Again, fatigue is something that is notable with this agent. And then a low risk of hypersensitivity reactions.

SG does carry the black box warnings for neutropenia and diarrhea.

Sacituzumab Govitecan and the UGT1A1*28 Genotype

The prescribing information for sacituzumab govitecan. It does mention UGT1A1 testing. UGT1A1 is an enzyme that breaks down that SN-38 payload of this agent, and genetic polymorphisms in this can result in reduced activity and therefore increased toxicity with this agent. In particular, patients that are *28/*28 diplotypes can have poor metabolism of the agent. So early identification may be helpful to identify those patients that may be at greater risk for toxicity, may need early dose reductions. This potentially could be baseline as patients start the agent, but certainly for patients that are presenting with excessive toxicity, it may be worth checking for this particular genetic polymorphism.

Managing Diarrhea With Sacituzumab Govitecan

We mentioned diarrhea an AE of interest here, and important to first consider grading. So we are looking at our stools over baseline. For patients with grade 1 or 2, so this would be less than or equal to six stools over baseline, we need to first consider the time frame for which the diarrhea is occurring. So for patients with an onset that is during or shortly after their infusion, this is generally considered an early or acute diarrhea that is associated with a cholinergic syndrome. Think of irinotecan here. This is very similar to what is occurring with SG. You do not necessarily need to use atropine as a primary prophylaxis here, but it should be the drug that we are reaching for than patients that experience this adverse effect. If patients have this prophylaxis with atropine during, future infusions would be recommended, and we can continue SG at the same dose.

For those patients with delayed onset, you are going to think of again, typically what we would do for irinotecan in this setting, where loperamide is our agent of choice as well as dietary management.

For patients that do not have resolution, you can escalate this to high-dose loperamide 4 mg at the time of first loose stool and then 2 mg every 2 hours around the clock. If that does not resolve things, you can look at other things like octreotide for refractory diarrhea, and certainly important to also still be considering infectious causes of diarrhea here.

For those patients that have greater than or equal to seven stools over baseline, so a grade 3 or grade 4, these are patients that are going to need to be more aggressive. So potentially considering hospital admission, octreotide, considering antibiotic therapy as well as here, and then potential considerations for dose reductions once you have patients who do not recover quickly or have grade 4 diarrhea.

Managing Neutropenia With Sacituzumab Govitecan

We mentioned another toxicity of interest with SG is neutropenia, which can potentially be severe. Onset here is about 2-3 weeks after treatment, median duration of six days. It is important to check a CBC with differential before dosing each treatment. So this would be on days 1 and 8 of each cycle. For patients that have an ANC of less than 1500/μL on day 1 or less than 1000/μL on day 8 or those patients that present with neutropenic fever, we should be holding drug. Management with G-CSF is important. Considerations for anti-infective therapy for patients that have febrile neutropenia.

And the dose reductions here are really dependent on how long it takes for the patient's counts to recover. So if the patient has delayed recovery by about 2-3 weeks, then dose reduction would be warranted.

Management of Additional Toxicities Associated With SG

Additional toxicities: We are not going to cover those in great detail, but risk of hypersensitivity reactions, so premedication is very important. Prolonged first infusion here at 3 hours and close observation of patients. Nausea and vomiting it is a high risk here, so a 3/4 drug regimen, as we previously discussed for T-DXd is also appropriate for this agent.

Management of Stomatitis/Mucositis Associated With Datopotamab Deruxtecan

From a prevention standpoint, you have a risk of mucositis with datopotamab deruxtecan. So advising the patient on steroid containing mouthwash four times a day. They should swish for one to two minutes and then spit. Another important here is cryotherapy, so holding ice chips or ice water in the patient's mouth during the infusion to try to limit blood flow to the mucosa.

Management would include continuing the steroid mouthwashes. If patients are not using that four times a day in the prevention setting, they should be doing that in the management setting, and may need pain management strategies.

Management of Ocular Toxicities Associated With Datopotamab Deruxtecan

And then finally, our ocular toxicity management here with datopotamab deruxtecan. Ophthalmologic exam is recommended at baseline and annually on treatment. Patients should also be using a preservative-free lubricant eye drop at least four times a day and as needed

Median onset is usually within about two months. It is often dry eye, but can be a number of other ocular complications. It is recommended that patients avoid contact lenses.

Management of Additional Toxicities Associated With Datopotamab Deruxtecan

There is a hypersensitivity risk with this agent, so premedication is necessary. Nausea and vomiting risk is also high here. So I would actually recommend a 3/4 drug regimen. This is now NCCN high emetic risk category. And then a low risk of ILD, and that really mirrors what we have talked about already with T-DXd in terms of management strategies.

Key Takeaways for Oncology Pharmacists on ADCs Targeting HER2, HER3, and TROP‑2

A number of takeaways here. The ADC class certainly has a growing role in the management of a number of different solid tumors. Most ADCs have unique side effect concerns, many that we have talked through today. A number of ADCs are currently under development, so we will likely see more indications for these in the coming months to years.