Brandon Scalea

Ibrutinib (Imbruvica) as a maintenance therapy for patients with mantle cell lymphoma (MCL) who respond to frontline induction therapy with or without autologous stem cell transplant (ASCT) appeared safe and feasible, according to the results of a recent study presented at the 2019 ASCO Annual Meeting.

Thirty-six patients with advanced stage (n = 28) and extranodal disease (n = 9), were included in this study; 50% of these patients had low-risk MIPI score (n = 18), while 19% (n = 7) and 31% (n = 11) had intermediate- and high-risk MIPI scores, respectively.

For induction, 47% of patients received bendamustine plus rituximab (Rituxan), 50% received a cytarabine-based regimen, and 3% received R-CHOP. Half of the patients underwent ASCT during their first complete remission (CR) prior to study enrollment.

Results from the initial safety report showed that 92% (n = 33) of patients achieved a CR, while 8% (n = 3) of patients had a partial response (PR) with induction therapy, with 1 PR to CR conversion observed with maintenance ibrutinib. At a median follow-up of 19 months, 67% (n = 24) of patients remain on ibrutinib maintenance therapy for a median 16.5 cycles (range, 1-49 cycles).

Treatment-related adverse events (TRAEs) led to dose reductions or interruptions in 69% (n = 25) of patients, with 25% (n = 9) needing to permanently discontinue therapy. One patient developed progressive disease on ibrutinib maintenance, and 1 patient died during therapy, noted Reem Karmali, MD, MS, who is lead study author and an assistant professor of medicine of Hematology and Oncology at Northwestern University Feinberg School of Medicine.

during the 2019 ASCO Annual Meeting, Karmali shared early data with ibrutinib maintenance therapy and highlighted recent advances and challenges in the treatment of patients with MCL.

: How would you describe the current MCL treatment paradigm?

MCL is a disease that remains incurable despite our best efforts, but several recent advances have been made. BTK inhibitors such as ibrutinib and acalabrutinib (Calquence) have shown profound activity in MCL. This isn't surprising since BTK is a very important part of B-cell receptor signaling, which we know is crucial to MCL differentiation, proliferation, and survival. BTK inhibitors are very active in relapsed/refractory MCL, with response rates in the 70% to 80% range. The question is, &ldquo;Can these agents can be moved into the frontline setting and improve outcomes in these patients?&rdquo;

This patient population as a whole is a significant unmet need because [the disease] is incurable. For the patients we treat, response rates are high, but relapse is very common. With subsequent lines of therapy, response rates tend to get shorter and shorter.

: Could you expand on some of the challenges that are still faced in this space?

We do get really high response rates with chemoimmunotherapy, but a big challenge is how to best treat patients in the frontline setting. There is no clear standard of care. Our treatments are variable, and they depend on several different patient factors. When we do see a patient with a relatively aggressive disease course who is symptomatic, treatments can range from rituximab monotherapy to chemoimmunotherapy with or without ASCT. It is unclear whether patients need to be consolidated with an ASCT and whether rituximab maintenance is appropriate, depending on what type of induction therapy the patient is started on. Certainly, there is an important ongoing US Cooperative Group study, in which investigators are looking to address this question of whether an ASCT is needed across the board in MCL.

Aside from picking the right therapy for patients, one of the biggest challenges is the fact that despite all of the effective therapies we have, patients still relapse. When they relapse, their outcomes tend to be quite poor.

Ibrutinib has significant activity in relapsed/refractory MCL, and that's on the basis of it being a BTK inhibitor, which we know targets an important protein in the disease. Ibrutinib is now being evaluated in the frontline setting, and the SHINE trial is looking at bendamustine plus rituximab with or without ibrutinib, and potentially ibrutinib maintenance following induction therapy. Other trials are looking at frontline ibrutinib as well.

: What was the rationale to use ibrutinib as a maintenance therapy?

With MCL, response rates are quite high with frontline therapy. The issue is that patients do relapse; that is to be expected. The question is whether we can improve upon frontline approaches. One way to do that is with maintenance therapy, and the optimal use of maintenance therapy [has not been] identified. We do know that rituximab improves progression-free survival (PFS) and overall survival (OS), but we want to know if we can do better than that. With ibrutinib having the level of activity that it does, it makes sense to consider it in the frontline setting. That's what we were hoping to do with our multicenter phase II study.

: Could you discuss this phase II trial and the initial findings presented at the 2019 ASCO Annual Meeting?

We looked at ibrutinib maintenance in treatment-na&iuml;ve patients and required intensive induction therapy to begin with. Patients could be treated with chemoimmunotherapy with or without an ASCT, and for those who achieved a CR or PR, they could be enrolled on the trial and receive ibrutinib maintenance at a dose of 560 mg daily for up to 4 years or until disease progression. We accrued a total of 36 patients. In these 36 patients, it is important to note that these patients had some high-risk features. Over 75% of our patients had advanced-stage disease, and 50% had either an intermediate- or high-risk histology. Approximately 25% of our patients had extranodal disease. When we look at the treatment patterns here, 47% of our patients were treated with bendamustine plus rituximab upfront, 25% were treated with R-hyperCVAD [rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone] and the remaining were treated with R-CHOP with or without cytarabine-containing cycles.

With induction alone, 33 out of 36 patients actually achieved a CR. Therefore, that supports the idea that we can get high response rates with chemoimmunotherapy induction alone. It is important to note that 50% of our patients did get ASCT, so that plays into the high response rates. There were 3 patients who had a PR. With our 36 patients who went onto ibrutinib maintenance, there was 1 conversion of a PR to a CR. Of the remaining 2 patients in PR, 1 stayed there, and 1 developed progressive disease. We were able to feasibly give ibrutinib maintenance for prolonged periods of time.

Thus far, we have 19 months of follow-up, and with that, 24 out of the 36 patients continued to be on ibrutinib maintenance, which speaks to the feasibility. Of those patients, there is 1 patient with progressive disease, and 1 patient who has died.

: What does the toxicity profile look like for this regimen?

For the most part, we found that the toxicities were in line with what one would expect from ibrutinib's safety profile. With treatment exposures, patients tolerated the drug quite well for the most part. With our follow-up of 19 months, the median number of cycles delivered were 16.5. In fact, one-quarter of patients have already completed 2 or more years of ibrutinib maintenance. With these patients, 2 of them have even completed the full 4 years with our data at this point. In terms of the toxicities, about two-thirds of patients had TRAEs that required dose modification. About 20% of patients required a permanent dose modification or reduction, and 25% of our patients actually needed permanent discontinuation of drug.

The main reason for discontinuation seemed to be atrial fibrillation, which we saw in 9 patients. For the most part, however, ibrutinib was well tolerated and in line with what one would expect with ibrutinib.

: What are the next steps for this research?

The study shows that ibrutinib maintenance is feasible and the toxicities are manageable. The key is going to be longer-term follow-up, as well as looking at minimal residual disease (MRD) status in our patients. Our primary objective was to look at efficacy, and this is defined by 3-year PFS rates.

However, one of our exploratory analyses was to look at MRD status and an IgH polymerase chain reaction&not;based methodology. We expect that MRD will give us a better idea if we can deepen response with ibrutinib maintenance, and we hope to show there is benefit by correlating MRD status with PFS and OS. If we can show this, it will make the argument that ibrutinib maintenance ought to be explored further.

: Beyond this work, were there any other studies presented at the meeting that you were particularly excited about?

In MCL, it was very exciting to see data on CAR T-cell therapy. There was a subset analysis of the TRANSCEND study, which looked at lisocabtagene maraleucel (liso-cel; JCAR017) a CD19 construct. The trial itself included [patients with] aggressive B-cell lymphomas, but [there was a] subgroup of [patients with] MCL.

What they found was that responses were quite high, despite the fact that this was a high-risk population. Patients had a high Ki-67 and all patients had been previously treated with ibrutinib. There were even patients with blastoid variant disease, and we know these patients have poor outcomes. Therefore, we saw that liso-cel was able to achieve high responses in these patients with durable responses in a few of them. This is an important area of research that needs continued exploration.

Karmali R, Abramson JS, Stephens DM, et al. Ibrutinib maintenance following induction for untreated mantle cell lymphoma (MCL): initial safety report.

. 2019;37(suppl 15; abstr 7542). doi: 10.1200/JCO.2019.37.15_suppl.7542.

Articles

Ibrutinib as a maintenance therapy for patients with&nbsp;mantle cell lymphoma who respond to frontline induction therapy with or without autologous stem cell transplant appeared safe and feasible, according to the results of a recent study presented at the 2019 ASCO Annual Meeting.

Ibrutinib Maintenance Appears Safe in MCL Following Induction Therapy

Dostarlimab (TSR-042), an investigational antiPD-1 therapy, demonstrated durable responses across subgroups of patients with&nbsp;microsatellite instability&ndash;high (MSI-H) and microsatellite stable (MSS) advanced or recurrent endometrial cancer, according to results&nbsp;from the phase I/II GARNET study.

The findings showed that treatment with dostarlimab (TSR-042) led to an overall response rate (ORR) of 29.6% in the general patient population. In the subgroup of patients with MSI-H tumors, the ORR was even higher at 48.8%; in those whose tumors were MSS, it was 20.3%. Furthermore, the disease control rate was 52.8% in the entire study population, 63.4% in those with MSI-H tumors, and 46.8% in patients with MSS tumors.

The median duration of response with the antibody was not reached at a median follow-up of 10 months. Of the overall population, 89% of patients remained on treatment for >6 months, while 49% continued for >1 year.

&ldquo;Taking into account the amazing results we have observed, there is a phase III trial that will analyze the activity of dostarlimab in patients with frontline advanced or recurrent endometrial cancer,&rdquo; said Ana Oaknin, MD, the lead author of the study.

, Oaknin, who is also head of the Gynecologic Tumors Unit, Medical Oncology Department, senior medical oncologist, and attending physician, at Vall d&acute;Hebron University Hospital, provided insight into the implications of the GARNET trial and the promise of dostarlimab in the field.

Could you discuss the GARNET trial and the key takeaways from this research?

: The GARNET trial was a very well-conducted phase I/II trial. It's the largest trial analyzing the role of antiPD-1 therapy in patients with advanced or recurrent endometrial cancer. In this trial, dostarlimab demonstrated clinically meaningful response rates in all the patients, regardless of MSI status. ORR in the overall population was about 30%. When we sort this out in terms of MSI status, we saw a 20% ORR in the MSS population and about 49% in those with MSI-H tumors.

The most important point to mention is the duration of the response. Although we haven't achieved the median duration of response, 89% of the responders have been on treatment for more than 6 months. Almost 50% have been on therapy for over 1 year. This is important for this poor-prognosis population who have advanced or recurrent endometrial cancer. Approximately 50% of the patients enrolled received at least 2 prior lines of chemotherapy; this means they are a heavily pretreated patient population.

Could you expand on the rationale for this study?

In endometrial cancer, we have patients with both MSS and MSI-H tumors. This is very important, and this is the key difference from pembrolizumab (Keytruda). The antiPD-1 therapy pembrolizumab is FDA approved under the umbrella of MSI-H solid tumors. However, pembrolizumab was not exclusively addressing endometrial cancer; it was addressing all solid tumors. We are looking to see [what the effectiveness of] anti&ndash;PD-1 [agents specifically, looks like] in endometrial cancer.

Why home in on the MSS population specifically?

We have previous data suggesting that patients with both MSS and MSI-H respond to antiPD-1 therapy. For example, the first trial with pembrolizumab, KEYNOTE-028, enrolled patients with MSS and MSI-H tumors. Another study in endometrial cancer combined pembrolizumab with lenvatinib (Lenvima). We saw responses in both of these patient populations, regardless of MSI status. To say that we have never seen immunotherapy response in the MSS population is not completely true.

Could you speak to the toxicity profile of dostarlimab?

Dostarlimab has a wonderful safety profile. In 70% of patients [in the GARNET trial], we observed some sort of treatment-related adverse events (AEs). However, in terms of immune-related AEs, less than 6% of patients developed grade 3 or 4 events. Remarkably, there were no deaths associated with the drug.

What is the agent&rsquo;s mechanism of action?

Dostarlimab is an investigational, humanized antibody that prevents the interaction between PD-1 and PD-L1. It also stimulates the immune system so that it will fight the tumor cells.

Oaknin A, Duska LR, Sullivan RJ, et al. Preliminary safety, efficacy, and pharmacokinetic/pharmacodynamic characterization from GARNET, a phase I/II clinical trial of the antiPD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-H and MSS endometrial cancer. Presented at: 2019 SGO Annual Meeting; March 16-19, 2019; Honolulu, HI. Abstract 33.

Dostarlimab (TSR-042), an&nbsp;investigational anti&ndash;PD-1 therapy, demonstrated durable responses across subgroups of patients with&nbsp;microsatellite instability&ndash;high and microsatellite stable advanced or recurrent endometrial cancer, according to results&nbsp;from the phase I/II GARNET study.

Dostarlimab Effective in Endometrial Cancer Regardless of MSI Status

Early data indicate that pembrolizumab (Keytruda) is a feasible option for patients with high-risk nonmuscleinvasive bladder cancer (NMIBC) who are unresponsive to Bacillus Calmette-Gu&eacute;rin (BCG), explained Arjun V. Balar, MD.

Data for cohort A of the phase II KEYNOTE-057 study, which were presented at the 2019 Genitourinary Cancers Symposium, showed that pembrolizumab induced a 3-month complete response (CR) rate of 38.8%. Among the 40 patients who achieved a CR at 3 months, 72.5% maintained a CR at a median follow-up of 14 months; median CR duration had not been reached at the time of presentation. However, 80.2% of patients had a CR lasting &ge;6 months.

Cohort A was comprised of 102 patients with NMIBC who had carcinoma in situ with or without papillary disease, said Balar, who is lead author of the trial. Patients received pembrolizumab at 200 mg every 3 weeks for up to 24 months. Grade 3/4 treatment-related adverse events were observed in 12.6% of patients; 1 death was considered to be related to treatment.

, Balar, director of the Genitourinary Medical Oncology Program,  and assistant professor in the Department of Medicine, at NYU Langone&rsquo;s Perlmutter Cancer Center, highlighted the KEYNOTE-057 study findings and provided insight into the role of immunotherapy in bladder cancer.

What was the rationale for the KEYNOTE-057 study?

KEYNOTE-057 aimed to test pembrolizumab, a PD-1 antibody, in a specific population of patients with NMIBC. These are patients with high-risk disease who have received BCG, an intravesical immunotherapy, in the past. These patients did not respond to BCG therapy. Historically, this population is treated with radical cystectomy, meaning surgical removal of the bladder. The reason we do this is because BCG-unresponsive disease has a natural history of progressing to muscle-invasive and eventually metastatic disease. Historically, radical cystectomy has been the only curative therapy available for these patients. In this context, pembrolizumab was tested as a means to achieve responses in the bladder and to help patients preserve their bladders.

What findings were presented at the 2019 Genitourinary Cancers Symposium?

I presented the preliminary analysis of 102 patients enrolled in cohort A of the study. Overall, this trial focused on 2 cohorts: cohort A focused on patients with carcinoma in situ with or without papillary disease, and cohort B focused on patients with papillary disease alone without carcinoma in situ. At a median follow-up of about 14 months, results for 102 patients in cohort A showed CR rates of about 40% with pembrolizumab. Additionally, the median duration of response at this point for CR is about 12.5 months. About 53% of patients will have CRs lasting 9 months or longer, which is quite encouraging. Of course, these are early data, and longer-term follow-up will be necessary.

What are the next steps for this research?

The next steps for this trial are to follow up on these patients who have achieved a CR and truly see how long and durable these responses are. It is also worth noting that this needs to be tested in a randomized setting, and that's what the KEYNOTE-676 trial is addressing. While this study has the potential for registration implications for pembrolizumab in this population, the randomized phase III study is also important. That will focus on patients with BCG-refractory disease after induction BCG and will be randomizing patients to receive either BCG reinduction alone or BCG reinduction plus pembrolizumab.

Is it likely that BCG will retain its role in this space?

BCG has a longstanding history in NMIBC treatment, and I believe it will have a firm role for decades to come; this is largely because it is still very active. In fact, about 70% of patients with carcinoma in situ will achieve a CR with BCG; it is very effective. What I envision in the future is not that BCG will get replaced, but that it will be augmented by the addition of other synergistic agents, like PD-1 antibodies.

Where do we stand in terms of predictive biomarkers of immunotherapy response in bladder cancer?

Certainly, in metastatic disease, some advancements have been made in terms of biomarkers to help us select who should and should not receive immunotherapy. For instance, PD-L1 expression certainly has value in the first-line metastatic setting. In high-risk NMIBC, I also presented data on the role of PD-L1 expression [at the 2019 Genitourinary Cancers Symposium]. Interestingly, we found that PD-L1 expression does not really predict the rates of CR in the bladder in this space. However, other biomarkers certainly need to be tested. For example, in the metastatic setting, we are also looking at tumor mutational burden.

Is immunotherapy the path forward in the treatment of patients with bladder cancer?

Immunotherapy is here to stay in bladder cancer, and it will be firmly established, even as frontline therapy. KEYNOTE-361 and IMvigor130 are 2 randomized trials comparing platinum chemotherapy alone with immunotherapy alone as well as platinum-based chemotherapy plus immunotherapy. Many of us in the field anticipate that platinum-based chemotherapy plus immunotherapy will be a new standard of care for patients in the frontline setting. However, even for patients who are not eligible for any chemotherapy, immunotherapy will still have a role, because we know the majority of patients who can't tolerate chemotherapy can feasibly receive immunotherapy.

Were there any other bladder cancer updates presented at that conference that you were excited about?

I was particularly excited about the data that Scott T. Tagawa, MD, MS, of Weill Cornell Medicine, presented from the phase I study of sacituzumab govitecan. This is an antibody-drug conjugate (ADC) that is particularly important for patients who are not responsive to PD-1 antibodies. We know that about 20% of patients will respond in the second-line setting to immunotherapy, meaning that we need treatment options for the remaining majority of patients. It seems that ADCs are quite attractive in terms of inducing responses and achieving disease control.

What does the outlook for patients with bladder cancer look like today versus 5 years ago?

The conversations I used to have with patients with metastatic bladder cancer were quite somber. We were talking about platinum-based chemotherapy and then single-agent chemotherapy or best supportive care upon progression. Many times, in the second-line setting, patients would opt for best supportive care because the treatments we had did not lead to meaningful responses and certainly not an improvement in survival.

Fast forward to 2019, we have 5 different agents targeting the PD-1 pathway available in the second-line setting and 2 of these agents are indicated for use in the frontline space. Several studies are also testing novel compounds that could potentially have significant impact in the clinic in the near future. These [approaches] include ADCs, targeted therapies that hit

, as well as other experimental immunotherapy compounds.

Balar AV, Kulkarni GS, Uchio EM, et al. KEYNOTE 057: phase II trial of pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-gu&eacute;rin (BCG).

. 2019;37(suppl 7, abstr 350). doi: 10.1200/JCO.2019.37.7_suppl.350.

Arjun V. Balar, MD,&nbsp;highlights the KEYNOTE-057 study findings and provides insight into the role of immunotherapy in bladder cancer.

Expert Discusses Promising Data With Pembrolizumab for Unmet Need in NMIBC

For several years, it has been known that tumor sidedness plays an integral role in the prognosis of patients with colorectal cancer (CRC). Research is now focusing on the role of primary tumor location in recurrence and how that information can be used to improve outcomes, said Scott Kopetz, MD, PhD, FACP.

&ldquo;We now have a much better knowledge of the biologic underpinning of, &lsquo;why does right versus left matter?&rsquo;&rdquo; said Kopetz, an associate professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. &ldquo;Together, with the strong clinical data and our understanding of the biology, we are at a point where our practice should be changing.&rdquo;

Several studies have indicated differences in response to targeted therapy between left- and ride-sided tumors. Patients with right-sided CRC often have poor responses to EGFR-targeted therapies, said Kopetz, and therefore should not receive agents such as cetuximab (Erbitux) or panitumumab (Vectibix), regardless of their molecular status. In contrast, EGFR inhibition appears to improve overall survival (OS) for patients with left-sided disease.

For example, results of a retrospective analysis of the phase III CRYSTAL trial, which examined first-line FOLFIRI plus cetuximab and irinotecan in patients with

wild-type disease, showed that patients with left-sided tumors had a better prognosis with the EGFR inhibitor cetuximab compared with those with right-sided disease.

&ldquo;In my practice, this information is indeed being utilized in the standard of care. For patients with a left-sided tumor, we are improving OS with EGFR inhibitors in the frontline setting,&rdquo; added Kopetz. &ldquo;I would discuss the perhaps longer duration of skin rash [with EGFR inhibitors for most patients], but for most, that improved OS is worth it.&rdquo;

, Kopetz explained the biologic difference between left- and right-sided CRC and highlighted recent research on tumor sidedness and its impact on clinical practice.

What are the differences between left- and right-sided CRC?

: In CRC, we've known for many years that there are differences between the left and the right side of the colon. The clinical implications of this have increasingly become apparent over the last several years. Part of the discussion is focused on what those [different] features are. What are the clinical data, and how do we actually use [these data to inform our actions] in clinic? We have known for years that the prognosis of patients with right-sided CRC is particularly poor and that patients have a shorter duration of survival and lower progression-free survival (PFS) with standard therapies. [Primary tumor location] also plays a role in recurrence after liver metastasis resection. The questions more recently have focused on how we should use this information and if there is an impact on chemotherapy.

Many studies and meta-analyses have been completed that have shown that there is differential response to targeted therapy on the right [versus the] left side of the colon. This is particularly evident with cetuximab or panitumumab. What we have seen is that patients with tumors on the right sideeven though they may have a tumor that doesn't have a

mutationstill have a poor response to EGFR inhibitors. This would manifest with lower PFS.

The question for all of this then becomes, &ldquo;Which therapies should we use for which patients?&rdquo; Similarly, we have seen that when [patients with] left-sided tumors are treated with EGFR inhibition compared with a VEGF inhibitor, there are improvements in OS. For example, the CRYSTAL study showed a fairly large improvement in OS for left-sided patients who were treated with EGFR inhibitors.

The second component is really understanding why this is. Certainly, compelling randomized data are always helpful. However, for me at least, it is always good to know why that is the case. Why are we seeing a difference in biology? Here, it's important to take a step back and recognize the differences between a right- and left-sided tumor. A left-sided tumor actually derives from very different embryologic remnants of this concept of a hindgut versus midgut, back to the embryology days of medical school. It is this idea that these are very different tissues that form, and that there are many differences in the environment of the normal gastrointestinal tract. This is manifested in several different ways. We also see differences in the epigenetics, the methylation that occurs with aging normal epithelium. There are differences in the exposure to different carcinogenic biallelic [mutations] in these patients.

Therefore, it's not surprising that the end result is a very different tumor. We see that the polyps are different on the right side, with a higher rate of sessile adenomas. Together, this helps explain differences in the mutation profile of the RNA-based classification.

:There is continued work to try to understand how tumor sidedness integrates with several different biomarkers that we have been interested in. For example, how do we integrate sidedness into our understanding of other molecular alterations and other epigenetic features such as microRNAs that have been proposed as predictive biomarkers? We are starting to realize that sidedness is incorporating many of these biomarkers that we had been interested in in the past. It provides a "poor man's biomarker" as we like to say, where just by looking where the tumor arises, we can understand a lot of biologic features. Several ongoing studies are trying to dissect out how much of the biology can be attributed purely to the sidedness [of the tumor]. How much benefit is still present in patients who test for benefit with EGFR inhibition?

What still needs to be understood about left- versus right-sided tumors?

: There are now questions about how to design studies that recognize the differences between left- and right-sided CRC. Now, we need to start asking questions within a very distinct subgroup about how to best optimize treatment. For example, within left-sided tumors, it may be that now there are biomarkers, such as the consensus molecular subtypes or

, that within a left-sided tumor may very clearly distinguish the potential for benefit with EGFR therapies relative to VEGF inhibition.

What is your take-home message to your colleagues?

: As we understand the context of colon tumors, we have to better understand the complexities of tumor location. We then need to start to understand how to apply some of those characteristics in our understanding of the carcinogenesis of these tumors to some other major issues we are facing in the field. One of those issues is early-onset CRC; increasingly, this is occurring in rectal, low-lying colon cancer. We don't have a good understanding as to why that is. However, as we understand the normal biology of these low-lying left-sided tumors, that helps us to better define the landscape of etiology for challenges like early-onset colon cancer.

Tejpar S, Stintzing S, Ciardiello F, et al. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials.

. 2017;3(2):194-201. doi: 10.1001/jamaoncol.2016.3797.

Scott Kopetz, MD, PhD, FACP, explains the biologic difference between left- and right-sided CRC and highlights recent research on tumor sidedness and its impact on clinical practice.

Brandon Scalea | Authors

Articles

Ibrutinib Maintenance Appears Safe in MCL Following Induction Therapy

Dostarlimab Effective in Endometrial Cancer Regardless of MSI Status

Expert Discusses Promising Data With Pembrolizumab for Unmet Need in NMIBC

Kopetz Sheds Light on Complexities of Tumor Location in Colorectal Cancer