Small-cell lung cancer in the relapse/refractory setting still is an aggressive cell malignancy. Uniformly, almost all patients relapsed. So far, we’ve had topotecan as the only FDA-approved agent in the past 2 decades in second-line small-cell lung cancer, platinum-sensitive disease. Again, the challenge, as you mentioned, with topotecan is due to its modest clinical benefit; the objective response from various clinical trials range anywhere from 5% to 24%, and median overall survival from other topotecan studies that we could see is 6 to 8 months. In these patients who have shorter overall survival, they show some significant hematologic toxicity as well. We needed different drugs in our armamentarium, especially in the second-line setting and that are non–immuno-oncology (I/O).

Recently, several new agents failed to demonstrate benefit in the second-line setting. Enter, lurbinectedin. Lurbinectedin is a selective inhibitor of oncogenic transcription. By inhibiting active transcription in the tumor-associated macrophages, lurbinectedin downregulates IL-6, IL-8, CCL2, and begets. As we all know, a small-cell lung cancer is transcription-addicted tumor. Recently, 4 molecular small-cell lung cancer subtypes have been defined by differential expression of 4 key transcription regulators. Initial lurbinectedin antigen tumor activity in small-cell lung cancer was observed in phase 1 to 2 study in combination with anthracycline/doxorubicin. Interestingly, that trial showed an objective response rate of 37% and a duration of response of 5.2 months.

Most recently, lurbinectedin was FDA approved. This approval was based on a multicohort basket study. Efficacy was demonstrated in a PharmaMar-led basket study, which is a multicenter, open-label, multicohort study, with only 105 patients with metastatic small-cell lung cancer who had disease progression on or after platinum-based chemotherapy. I was one of the co-investigators for this clinical trial for this multiarm clinical trial that enrolled not only small-cell lung cancer patients but also aggressive tumor types like Ewing sarcoma and germ cell tumors. Again, this specific small-cell lung cohort enrolled 105 patients with metastatic SCLC (small-cell lung cancer) vibrations with metastatic small-cell lung cancer. Patients received 3.2 mg/m2 of lurbinectedin by intravenous infusion every 21 days until disease progression of unacceptable toxicity. The main outcome measures were confirmed overall response rate as determined by the investigative assessment using the RECIST version 1.1 and response duration. Among the 105 patients enrolled, the objective response rate was 35%, with a median response duration of 5.3 months. The objective response rate for independent review committee was 30%, with the median response duration of 5.1 months. The most common adverse event that we saw more than 20% of the time in these patients enrolled on the clinical trial was myelosuppression. This is a chemotherapy, and the most common adverse effects were myelosuppression, fatigue, and some patients had elevated creatinine. We need to be cognizant that these patients have all come from cisplatin-, platinum-, and etoposide-based therapy. They have borderline renal function, including some liver function abnormalities and this glucose, nausea, decreased appetite… Vomiting and cough were also seen together with diarrhea.

The recommended phase 2 dose for the FDA label was 3.2 mg/m2 every 21 days. It received an accelerated FDA approval. The benefit observed with lurbinectedin compares favorably with what we historically see with topotecan. This is a current standard of care in terms of both anti-tumor activity and safety. Lurbinectedin is FDA approved, and it was also added to the NCCN (National Comprehensive Cancer Network) guidelines on June 7, 2020.

Let’s talk to Dr Ganti and Dr Chiang on how they think the approval will impact the treatment armamentarium in small-cell lung cancer. First, Dr Ganti.

 Lurbinectedin is the first drug that has been approved in this setting for a long time, and we are all excited about it. We finally have some alternative to topotecan. As Dr Chiang mentioned earlier, topotecan was available, but no one really liked it because of the myelosuppression and the toxicity associated with it. As you mentioned earlier, the outcomes were not great. Response rates ranged between 10% and 25%, with a median overall survival between 6 and 8 months. There was a big need to improve upon that. Lurbinectedin seems to have done that, at lease in some measure. As far as my practice is concerned, I will be using more of this drug in this cohort of patients. From the phase 2 basket trial that you just described, it appears that the adverse effect profile was very manageable. Myelosuppression was not as significant compared with topotecan, with the understanding that these 2 drugs have not been compared head-to-head in a clinical trial. There is an ongoing phase 3 trial comparing the combination of lurbinectedin and doxorubicin with topotecan, and that will give us more details and a better idea of what the exact benefit of lurbinectedin is. Based on this phase 2 data, I think that this would be a useful addition to our armamentarium in regard to small-cell lung cancer.

 Do you have any other insight into this drug, Dr Chiang?

 I think this is a great option for our patients. We have this epic treatment plan built, we’ve been pushing to get this drug into patients, and it’s actually available. I just got an email this week. We’re very excited. I think that patients are excited. It’s well tolerated, and 35% overall response rate is much better than what we’ve seen with our standard agents. I think this is a great option.

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Data on FDA Approved Therapy for Relapsed/Refractory SCLC

 Thank you, Dr Chiang and Dr Ganti for sharing your perspectives on front-line management of small-cell lung cancer. Now that we’ve discussed frontline therapy, the next topic is the most challenging one in the clinic and for research, which is the relapse/refractory small-cell lung cancer. Dr Chiang, would you use an immunotherapy (I/O) regimen after progression chemo or chemo-I/O combination?

 I do have an investigator-initiated trial looking at IPI/NIVO (ipilimumab/nivolumab) for relapse disease with the idea of utilizing an anti–CTLA-4 and anti–PD-1 combination to salvage patients who progressed on ATEZO (atezolizumab). Obviously, the CASPIAN data with DURVA (durvalumab) and TREME (tremelimumab) was negative, but we’ve also seen in other instances that the DURVA/TREME combination may not be so active and mystic. I do think that IPI/NIVO has had a good track record in CheckMate-032 for small-cell, and this particular trial is really looking at biopsies and pretreatment to look at whether the ratio of CD8 to FOXP3 cells—the ratio of effector to T regulatory cells—can correlate with response, with the clinical question being can you use a combination to salvage progression on 1 single agent? I’ll comment in terms of looking at mechanisms of acquired resistance in non–small-cell. There are data in colorectal tumors that impaired antigen presentation, MHC (major histocompatibility complex), or beta-2 microglobulin defects that can be a mechanism. That’s something we’re interested in looking at because we know that, unfortunately, while we’re looking at the tail of the curve, the current data show that almost all these patients will progress and require second-line therapy if they have the performance status. There’s a possibility that we can salvage with combination I/O. Certainly, if we learn from the non–small-cell, if you use combination chemo-I/O upfront, then you usually go to a chemo regimen. I think we have some exciting new chemo options, at least one that we’ll talk about today, and then we may need to recycle some things so our patients who have good performance status can still continue with treatment.

One more question I had for you is, would you think about re-challenging with platinum and etoposide combination for the second-line?

 For small-cell, we do have literature talking about platinum-sensitive disease, which is typically if you are strictly looking at 6 months, although a lot of trials look at recurrence within making it through the 3-month range. I do think that is an approach that we’ve used with pre-immunotherapy. We don’t know how it looks for patients on maintenance ATEZO or maintenance DURVA. I think we would probably add back the platinum if it’s been a long time, for example, 3 or 6 months, but this is a bit of a data-free zone because we didn’t have the IO when we were looking at the platinum-sensitivity before.

 Do you have any insights to share on second-line therapy for small-cell, Dr Ganti?

 I have a slightly different take than Dr Chiang about re-challenging with immunotherapy. If you look at CheckMate-032 in the relapse setting, the addition of ipilimumab and the nivolumab added the increased response rate but did not necessarily increase the duration of response of survival. In that setting, adding IPI in someone who’s progressing while on maintenance DURVA or ATEZO… I’m not sure that I would necessarily use that. I would use a different agent in that setting. As far as re-challenging with platinum/etoposide is concerned, I agree with Dr Chiang that if it is for more than 6 months, and sometimes even more than 3 months, since the last dose of these agents, I would tend to re-challenge with them. If someone is on maintenance immunotherapy when they progress, I would use their duration from the last chemotherapy cycle to decide whether or not to re-challenge with platinum/etoposide. If I decide to use platinum and etoposide, I would not necessarily continue with checkpoint inhibitor; I would use chemotherapy alone. Again, there is very little evidence one way or the other because, like Dr Chiang said, the data on re-challenging with platinum/etoposide was done in an era when we did not have immunotherapy, and those patients were not on any treatment when they relapsed and were re-challenged with platinum/etoposide.

 I just want to make sure that I had responded about IPI/NIVO. That’s within the context of a clinical trial. Off-trial, I would not give IPI to those patients. I would move on to chemotherapy, and I think that the classes of chemotherapy that are effective in relapse small-cell are… Topotecan was previously the only FDA-approved therapy. There are a lot of people who don’t like topotecan and don’t think it’s effective, but it is an option for the patient to go on an oral therapy and take a break from IV therapy. I think taxanes are very active for small-cell. Temozolomide is also a good option, especially if you are worried about progression or disease in the brain. There are approaches with maintenance strategies combining I/O with PARP inhibitors that are now available in clinical trials, so I think there are different options for these patients if they have the performance status. I will say, just anecdotally, I had a patient who came off of maintenance atezolizumab, went onto my IPI/NIVO trial, and then subsequently went on topotecan and had an extended response to topotecan, over 8 months. I don’t know what these checkpoint inhibitors are doing to sensitize the body to boost them when you have chemotherapy and cytotoxic chemotherapy subsequently. I think postprogression chemo added to or after immunotherapy is very interesting.

Use of I/O Regimen in Relapsed/Refractory SCLC

 One more question I have now is, what tactical advice would you share about the expected toxicity management, especially if you want to combine them with radiation all in the COVID-19 (coronavirus disease 2019) era?

 One of the things that becomes difficult in the COVID-19 era is if you see pulmonary infiltrates, you don’t know what they are. Of course, it’s important not just to trust your scans but also talk to the patient, see what other kinds of symptoms that they are having. My approach has been that if they have not had other classic symptoms of an infection, like fever, then I would not necessarily blame it on COVID-19, but rather consider this immune-related pneumonitis. I would have an intermediate threshold for stopping the immunotherapy because, yes, it is very beneficial, but at the same time, you don’t want pneumonitis to get out of hand. I would monitor them closely, check their symptoms, monitor that; this becomes even more important in the setting of those patients we give thoracic radiation to. You have to be very clinically alert in distinguishing between the pneumonitis due to checkpoint inhibitors due to radiation if you offer them thoracic radiation. With COVID-19, I’m not aware of any CT scan findings that would differentiate 1 from the other, except that radiation pneumonitis is within the radiation field, and if you see something outside, you have to worry about other things. That is 1 practical aspect.

The other things is, we’ve been taught that we have to use steroids for immune checkpoint inhibitor–induced toxicity. At the same time we have to be a little concerned about the possibility of higher doses of steroids affecting the response rate to the treatments. That’s a fine balance. What I tend to do is if I have a patient who is overtly symptomatic, then I would stop the checkpoint inhibitor and start them on steroids and try to ween them off steroids as quickly as possible. Of course, we need to understand that some of these patients need a much longer taper and then hold them off. Whether to rechallenge with the immunotherapy drug depends on how severe their initial symptoms were and how quickly they respond to steroids. So those are some of the practical tips I’ve learned while using these drugs in this particular setting, especially in the COVID-19 era.

 Perfect. Thank you, Dr Ganti. Do you have anything else to add, Dr Chiang?

 These drugs are very well tolerated. The grade 3, 4 in the studies, adverse events were really in the 2% to 5% range with rash, hepatitis, and colitis the main things that people were worried about. Obviously, we do worry about pneumonitis. In the COVID-19 era, we see some of our patients with telehealth. Just to follow what Dr Ganti said, these are patients probably who would be better not being seen by telehealth but in person, so you can really evaluate their oxygen saturation and their vitals, listen to their lungs, and see how they’re doing. With regard to the steroids, many of our protocols allow patients who are on prednisone of 10 mg or the equivalent, or below, to be on trial getting checkpoint inhibitors. There have been data within that realm to show that that seems to be okay. Rechallenge is possible, although I think you really have to be careful. Hepatitis is not something that we generally rechallenge for.

Advice on Toxicity Management for SCLC Therapy

 Distilling from all these trials, what is your personal approach to treatment in a newly diagnosed patient that presents to your clinic? Let’s take it from Dr Ganti first.

 There are a lot of things to consider than starting patients on treatment. One of the important things I have encountered in practice from a logistics standpoint is a lot of these patients may have to start treatment in the hospital, and there are some logistical issues with getting the checkpoint inhibitors while the patient is in the hospital. Oftentimes we have to start them with platinum/etoposide, get the first cycle in the hospital, and then once they are in the outpatient setting, add the check point inhibitor afterward.

As far as deciding which check point inhibitor to use, the 1 striking thing I’ve found from the IMpower133 and CASPIAN studies is that even though there were some slight differences in the inclusion and exclusion criteria—as Dr Chiang mentioned, asymptomatic brain metastases were allowed in the CASPIAN study—it is striking how similar those results are, suggesting that this benefit with check point inhibitors is real benefit. Oftentimes you see when you have different studies that some show more benefit compared with the others, but if you look at all 4 of these trials that we’ve talked about and forget the statistical significance part of it, if you look at the magnitude of benefit—the difference in benefit, the absolute overall numbers—they are so strikingly similar to one another, suggesting that this is a real benefit. Based on that, I would suggest that all these patients be treated with a check point inhibitor in the first-line setting. My personal preference has to do with where I live and the distances people have to travel to come visit me. If you look at IMpower133, it was an every-3-week regimen, with the maintenance given every 3 weeks. The CASPIAN study was chemotherapy given every 3 weeks, with maintenance given every 4. I have had patients tell me that they would do whatever if they can make fewer trips. For patients who come to me from 3, 4 hours away, I tend to use durvalumab, whereas with patients who live close by and don’t have problems making the trip, either option would be fairly reasonable.

 Thank you so much, Dr Ganti. Let’s turn to Dr Chiang. Dr Chiang, which regimen are you using in your own patients, and does your clinical experience match with what was seen in the clinical trials that we just saw?

 Yeah. The fact that both IMpower133 and the CASPIAN trial showed very similar overall survival provides good options, validation No. 1, and good options for our patients. Both of them are good drugs. Within the non–small-cell space, we’ve had experience using both drugs. Atezolizumab is very well tolerated, and durvalumab we’ve used for consolidation for stage III non–small-cell, also well tolerated. I will say that with the COVID-19 (coronavirus disease 2019) in this era, we did look at converting our atezolizumab from every-3-week to every-4-week administration. For durvalumab, we also considered doing it every 6 weeks just to keep people out of the office and out of the health care system if we could. For patients with asymptomatic brain metastases, I would prefer durvalumab.

I agree with Dr Ganti that many of these patients are sick and started out in the hospital. We can’t start the immunotherapy in house, so we end up starting it afterward. Are they interchangeable? I don’t think we have information that says that 1 is clearly different from the other. Aside from the brain metastases issue, we could probably use either 1. I have used both. Additionally, we used the atezolizumab that had FDA approval sooner, but now I have been using durvalumab as well. I would just mention that 1 issue that constantly comes up in our tumor board is if the patient has persistent disease, do you consider thoracic consolidation? A fight we have every week is between the radiation oncologists and the medical oncologists. The radiation oncologists say, “Gee, it’s certainly tolerated well with immuno-oncology and the radiation, and we think we can have a better benefit.” But clearly, the trials did not include thoracic consolidation, so if you’re a purist, you really try to follow the data. For me, unless there’s a clear reason to use radiation—for example, if the patient is symptomatic and there is a need for some local effect—then I hold off on that, but I know that’s a bone of contention. I don’t know what you guys do.

 I agree. That has been a challenge. What I tend to do is, if someone has had good response outside the chest and has a less severe disease within the chest—of course, we don’t know if this is inflammation with that tumor tissue—I at least talk to the patient about possibly considering thoracic radiation. I understand that neither of the trials allowed it, so it is a data-free zone if you will, but given what we know about the benefits of thoracic radiation and the kinds of people it will benefit, I would tend to offer that small portion of patients thoracic radiation. If I see a good response in the thorax, more than 90% shrinkage and good disease response outside the chest, then I’m not so sure those individuals necessarily need added radiation to the immunotherapy. I agree that we’ve done radiation with immunotherapy in multiple other diseases, and the combination seems to be well tolerated. We’ve not had too many adverse effects in that setting, so I don’t have any problems with that, but given that these trials did not include them, I would not offer it in everyone, just a select portion of patients for whom I think adding the radiation would help improve the quality of their response.

Personal Approach in Treatment Compared to Clinical Trials

 Turning to Dr Ganti, can you comment on the recent progress in treatment of extensive-stage small-cell lung cancer with the availability of immunotherapy-chemotherapy combinations?

 Sure. Small-cell lung cancer, especially extensive stage, was in need of some advances in the treatment paradigm. For the last 25 years, we’ve been using platinum and etoposide as our backbone regimen. Until recently, there was no other treatment that was shown to be superior to this combination, and it was not for lack of trying. The first study that showed a benefit over standard platinum/etoposide was the IMpower133 study, which showed that adding atezolizumab, a checkpoint inhibitor, to platinum/etoposide increases overall survival. Since then, there have been at least 2 other trials. The CASPIAN study that showed that adding durvalumab to platinum/etoposide was better than platinum-etoposide alone. More recently as the ASCO (American Society of Clinical Oncology) annual meeting a couple of months ago, the addition of pembrolizumab to the same platinum/etoposide backbone regimen was associated with an improved progression-free survival (PFS) compared with platinum/etoposide alone. A smaller randomized phase 2 study looked at nivolumab/platinum/etoposide and showed an improvement in progression-free survival and improvement in overall survival with the addition of nivolumab. We have 4 trials with different checkpoint inhibitors that suggest that adding a checkpoint inhibitor to platinum/etoposide is better than chemotherapy alone. Of these 2 drugs, durvalumab and atezolizumab have FDA approval in this indication.

 Thank you so much. Do you have any comments, Dr Chiang?

 Sure. I think this is a very exciting time, as Dr. Ganti said, for small-cell. We’ve had several approvals in the past year and that, compared to 30 years of no approvals, so we’re very excited. The IMpower133 trial and CASPIAN trial have really defined the frontline standard of care. The IMpower133 trial showing OS (overall survival) of about 12.3 months versus 10.3 months and a hazard ratio of 0.76. The updated CASPIAN data just presented at ASCO showing 13 months versus 10.3 months overall survival with a hazard ratio of 0.73. It’s interesting. The point made on the CASPIAN trial is that the separation of curves at 2 years, that survival improved from 14% to 20% on the experimental arm versus control arm. That is that tail of the curve. It’s something we’re really excited about and looking for in this population, which clearly doesn’t have the median overall survival; it’s about a little over a year. We definitely need more research and ongoing investigation into to new therapeutic agents and options, but the addition of immunotherapy does help us have hope that there are some patients who can have really long-term survival.

For the CASPIAN trial, the combination of tremelimumab and durvalumab did not help, so adding that anti—CTLA4 antibody did not help. Just a word on KEYNOTE-604, which was the pembrolizumab trial: This was not statistically significant but certainly did have the overall survival and progression-free survival trends in the right direction. It looks very promising, but because of the way the study was conducted, it did not have statistical significance. The nivolumab/platinum/etoposide trial, ECOG-5161, was phase 2 but looked promising. The primary end point was PFS. The last thing I would add is that we have a couple of options upfront. How do you decide? It’s not absolutely clear that 1 is much better than the other, which is great. We have options for our patients. I think 1 of the differences in the CASPIAN trial was that it did allow asymptomatic brain metastases. If I have a patient who does have asymptomatic brain metastases, I might be more inclined to use that durvalumab regimen in combination with chemotherapy.

Recent Progress in the Treatment of SCLC

® presentation, “Recent Advances in Small-Cell Lung Cancer.” We are going to spend the next 45 minutes focused on recent advances concerning both frontline and relapsed/refractory disease. I am your host, Dr Vivek Subbiah, a medical oncologist and clinical trials investigator from The University of Texas MD Anderson Cancer Center. Today, I am joined by my colleagues, who are experts in thoracic oncology: Dr Anne Chiang from the Yale University School of Medicine Smilow Cancer Hospital in New Haven, Connecticut; and Dr Apar Ganti from the University of Nebraska Medical Center in Omaha. Let’s get started.

Small-cell lung cancer (SCLC) is a highly aggressive, lethal, and widely metastatic lung cancer that kills an estimated 250,000 people worldwide yearly. This is based on the fact that small-cell lung cancer has an estimated 15% global lung cancer incidence and a 7% 5-year survival. Small-cell lung cancer is categorized by rapid tumor growth, high vascularity, genomic instability, early metastatic dissemination, and almost universal inactivation of 

 genes and frequent disruption of several characteristics signaling networks. Almost all patients with small-cell lung cancer are current or former heavy smokers. At this point, after decades of research, the prognosis for small-cell lung cancer patients remains poor, and treatment options are limited. Small-cell lung cancer is associated with more paraneoplastic syndromes than any other cancer type. To begin, let’s jump on frontline therapy for extensive-stage small-cell lung cancer.

Around 70% of patients with small-cell lung cancer present with extensive-stage disease on diagnosis. The remaining 30% of patients have limited-stage disease, in which the tumor involvement is confined to 1 hemithorax and can be treated in a tolerable radiation field. Let’s turn to an expert, Dr Apar Ganti from Nebraska. What has been the progress in identifying predictive biomarkers? Do you test for PD-L1 or tumor mutation burden (TMB) in small-cell lung cancer?

 Currently, there is no evidence to suggest that either PD-L1 levels or tumor mutation burden have a predictive role in small-cell lung cancer. Unlike non–small-cell lung cancer, where we know that increasing PD-L1 expression predicts increased response to checkpoint inhibitors, we do not have the same evidence yet in small-cell lung cancer. None of the recent frontline trials used either PD-L1 expression or tumor mutation burden as inclusion criteria, so the current standard of care is to not to check for either PD-L1 expression or tumor mutation burden in this cohort of patients.

 We know that small-cell lung cancer is an immunogenic tumor with high somatic mutation rates. This is mainly because these patients have tobacco exposure or a history of tobacco exposure resulting in potential new antigens, the presence of suppressed new responses, and the occurrence of paraneoplastic disorders. Dr Chiang, can you comment on PD-L1 and TMB in SCLC?

: As Dr Ganti said, PD-L1 expression is not predictive. It’s typically very low in small-cell, so that’s different from non–small-cell. There is 1 trial with pembrolizumab that looked at the combined positive score to take into consideration both the expression on tumor cells and immune cells. But on the whole, if you look at the regular assays that we use, small-cell is pretty much a negative tumor. There’s a lot of interest in TMB. It’s not standard of care, but the idea is that small-cell is a tumor. It’s within the top 10 tumor types. If you have a very high TMB and the presence of multiple antigens, there are more neoantigens that can boost the immune system response. Look at the original CheckMate 032 trial, which was presented at World Conference on Lung Cancer a couple of years ago. If you look at the response rate to immunotherapy, either nivolumab alone or nivolumab/ipilimumab, that was much higher in the TMB high—up to 46% response rate in that population. It’s a very intriguing marker. We’ll talk a little about that in the frontline trials that we’ll discuss, but so far, it hasn’t changed our standard of care to order those studies upfront on small-cell.

Introduction and Identifying Predictive Biomarkers

Vivek Subbiah, MD, associate professor in the Investigational Cancer Therapeutics Department and center clinical medical director of the Clinical Center for Targeted Therapy, of the Cancer Medicine Divistion, at The University of Texas MD Anderson Cancer Center, discusses the utility of tivozanib (Fotivda) in renal cell carcinoma (RCC).

An unmet need for patients with RCC in the second-, third-, and fourth-line setting remains, says Subbiah. With multiple TKIs FDA approved and available in the clinic, it is a phenomenal time to think about how to sequence and combine these drugs. The goal is to offer the right treatment to the right patient at the right time, adds Subbiah. In this context, the phase 3 TIVO-3 study, results of which were published in the 

now comes into play. In this study, investigators compared the efficacy and safety of tivozanib with sorafenib (Nexavar) in the treatment of patients with metastatic RCC in the third- and fourth-line setting. Results showed a median overall survival of 16.4 months with tivozanib and 19.7 months for sorafenib (HR, 0.99; 95% CI, 0.76-1.29; 

= .95). At a median duration on study of 32.5 months, 20 patients remained progression free on tivozanib versus 2 patients on sorafenib.

Previously, results from the phase 3 TIVO-1 study led to the approval of tivozanib in the first-line setting in Europe, Subbiah adds. In the United States, however, that was not the case, says Subbiah. Interestingly, the TIVO-3 study was one of the first phase 3 studies to randomize patients to sorafenib or a VEGF TKI in post-immunotherapy patients in the third-line and beyond setting. Again, that is why this study is significant, because it demonstrates that VEGF is still active and a VEGF inhibitor with a longer half-life is still active in the relapse/refractory space, explains Subbiah. The long-term follow-up data from this trial is expected in the future, thus generating a great deal of excitement in this space. These results may shed further light on how best to sequence these therapies, says Subbiah. That is how tivozanib becomes important in the relapsed/refractory setting of RCC, concludes Subbiah.

Vivek Subbiah, MD, discusses the utility of tivozanib in renal cell carcinoma.

Dr. Subbiah on the Utility of Tivozanib in RCC

Vivek Subbiah, MD, associate professor in the Investigational Cancer Therapeutics Department and center clinical medical director of the Clinical Center for Targeted Therapy, of the Cancer Medicine Divistion, at The University of Texas MD Anderson Cancer Center, discusses the utility of tivozanib (Fotivda) in renal cell carcinoma (RCC).

An unmet need for patients with RCC in the second-, third-, and fourth-line setting remains, says Subbiah. With multiple TKIs FDA approved and available in the clinic, it is a phenomenal time to think about how to sequence and combine these drugs. The goal is to offer the right treatment to the right patient at the right time, adds Subbiah. In this context, the phase 3 TIVO-3 study, results of which were published in the 

now comes into play. In this study, investigators compared the efficacy and safety of tivozanib with sorafenib (Nexavar) in the treatment of patients with metastatic RCC in the third- and fourth-line setting. Results showed a median overall survival of 16.4 months with tivozanib and 19.7 months for sorafenib (HR, 0.99; 95% CI, 0.76-1.29; 

= .95). At a median duration on study of 32.5 months, 20 patients remained progression free on tivozanib versus 2 patients on sorafenib.

Previously, results from the phase 3 TIVO-1 study led to the approval of tivozanib in the first-line setting in Europe, Subbiah adds. In the United States, however, that was not the case, says Subbiah. Interestingly, the TIVO-3 study was one of the first phase 3 studies to randomize patients to sorafenib or a VEGF TKI in post-immunotherapy patients in the third-line and beyond setting. Again, that is why this study is significant, because it demonstrates that VEGF is still active and a VEGF inhibitor with a longer half-life is still active in the relapse/refractory space, explains Subbiah. The long-term follow-up data from this trial is expected in the future, thus generating a great deal of excitement in this space. These results may shed further light on how best to sequence these therapies, says Subbiah. That is how tivozanib becomes important in the relapsed/refractory setting of RCC, concludes Subbiah.

Vivek Subbiah, MD, discusses the utility of tivozanib in renal cell carcinoma.

Dr. Subbiah on the Importance of Tivozanib in RCC

Vivek Subbiah, MD, associate medical director, Clinical Center for Targeted Therapy, assistant professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the safety and efficacy findings of BLU-667 in 

-altered solid tumors in an interview during the 2018 AACR Annual Meeting.

According to the findings from the open-label, first-in-human, phase I ARROW trial, the next-generation tyrosine kinase inhibitor BLU-667 appeared to be well tolerated and had broad clinical benefit among patients with advanced,

-altered solid tumors who progressed on prior therapies.

BLU-667 demonstrated broad antitumor activity with a best overall response rate (ORR) of 37% (95% CI, 20%-56%) in those with 

alterations who received doses ≥60 mg and had at least 1 post-baseline response assessment (n = 30). Patients with non—small cell lung cancers and medullary thyroid cancers had a best ORR of 50% and 40%, respectively.

Vivek Subbiah, MD, associate medical director, Clinical Center for Targeted Therapy, assistant professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the safety and efficacy findings of BLU-667 in RET-altered solid tumors in an interview during the 2018 AACR Annual Meeting.

Vivek Subbiah, MD, MD Anderson Cancer Center

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