Three women taking a selfie at bruch

Prevention

Aspirin Linked to Long-Term Reduction in Cancer Risk in Patients With Hereditary Cancer Predisposition

Lynch syndrome is an inherited condition associated with an increased risk of multiple types of cancers, including colorectal cancer. The lifetime risk of colorectal cancer is estimated to range from 20% to 80% among patients with this condition versus 4%-5% for the general population.37,38 Accumulated data from observational studies and registries suggest a protective benefit associated with aspirin in patients with Lynch syndrome.39 Twenty-year follow-up was planned as part of the CAPP2 study (ISRCTN registry, number ISRCTN59521990), which included 427 individuals randomly assigned to receive daily aspirin or placebo for 2 years. The analysis showed a significant, meaningful decrease of 44% in colorectal cancers among Lynch syndrome carriers who took aspirin compared with those who took a placebo.40 This benefit took more than 5 years to become detectable but persisted
beyond 20 years. Serious adverse events were comparable for the two groups. The optimal dosage and treatment duration remain to be determined.

Combination Therapies​

Tucatinib plus standard therapy delays progression of brain metastases in patients with HER2-positive breast cancer.​
Brain metastases have long been a challenge for patients with HER2-positive breast cancer, developing in up to half of patients.41 These metastases progress quickly, typically within 6-12 months, due to a lack of effective treatments beyond localized therapy.42,43

Results from the randomized, placebo-controlled HER2CLIMB study (ClinicalTrials.gov identifier: NCT03975647),44 changed this by showing that adding a new HER2 targeted therapy, called tucatinib, to standard trastuzumab and capecitabine significantly reduced the risk of brain metastases progression or death. Over the course of the study, this risk fell by just over two thirds (68%) compared with patients who received placebo with trastuzumab and capecitabine. Patients taking tucatinib also had longer overall survival—18.1 versus 12.0 months.

These strong efficacy results established tucatinib as a new standard of care for patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. The FDA approved tucatinib in combination with trastuzumab and capecitabine for this patient population.45

Immunotherapy before surgery may improve prognosis of early-stage, triple-negative breast cancer.
Triple-negative breast cancer is the most aggressive subtype of breast cancer.46 In this cancer, the three most common growth factor receptors that drive breast cancer growth are not expressed—estrogen receptor, progesterone receptor, and HER2. Advanced triple-negative breast cancer has an extremely poor prognosis,46 so preventing progression in patients with early-stage disease is a high unmet medical need and a critical area for research. A number of studies have demonstrated that achieving pathologic complete response—when no cancer cells remain in the breast or lymph nodes—from chemotherapy given prior to surgery (neoadjuvant chemotherapy) is strongly associated with better prognosis.47–49

The immunotherapy drug pembrolizumab has shown promise in patients with early triple-negative disease.50 With the phase III KEYNOTE 522 trial (ClinicalTrials.gov identifier: NCT03036488),51 patients with stage II or III triple-negative breast cancer were randomly assigned to receive neoadjuvant standard platinum-based chemotherapy with either pembrolizumab or placebo, followed by anthracycline and cyclophosphamide with either pembrolizumab or placebo. Patients then went on to surgery, followed by treatment with pembrolizumab or placebo. The addition of pembrolizumab to chemotherapy improved pathologic complete response (64.8%) compared with chemotherapy alone (51.2%) as well as event-free and overall survival. Pathologic complete response occurs when no signs of cancer can be found in tissue samples. These promising results suggest that the combination of chemotherapy with immunotherapy may improve long-term outcomes for patients with this disease.

This study supports progress in an area noted in ASCO’s Research Priorities to Accelerate Progress Against Cancer, most notably the increased use of immunotherapy in a difficult-to-treat disease. Patients who have a complete response to neoadjuvant (given prior to surgery) chemotherapy are more likely to have the option of breast conservation than those who have significant residual disease. 

CDK4/6 inhibitor reduces risk of early recurrence for high-risk early-stage HR-positive, HER2-negative breast cancer. 
It is estimated that up to 20% of patients with hormone receptor (HR)–positive, HER2-negative breast cancer will experience disease recurrence in the first 10 years after diagnosis.52 These recurrences are typically distant metastases and are often incurable. Given that over 150,000 patients are diagnosed with HR-positive HER2-negative breast cancer each year in the United States alone, advances in the treatment of this disease may have a substantial impact on the population.53

Abemaciclib is a cyclin-dependent kinase 4 and 6 (CDK4/ 6) inhibitor that works by blocking certain proteins to slow down the growth of cancer cells.54 It is approved by the FDA as initial therapy for advanced HR-positive, HER2-negative breast cancer based on clinical trials that showed substantially improved outcomes for women treated with abemaciclib and traditional endocrine therapy compared with endocrine therapy alone.55

In the phase III randomized monarchE trial (ClinicalTrials.gov identifier: NCT03155997),56 researchers evaluated the addition of abemaciclib to standard adjuvant endocrine therapy in patients with HR-positive, HER2-negative early breast cancer with positive lymph nodes and a high risk of recurrence within 5 years of cancer diagnosis. Abemaciclib combined with endocrine therapy showed a significant improvement in invasive disease-free survival (92.2 at 2 years [92.2%] compared with standard therapy alone [88.7%]). Most patients in the trial experienced at least one treatment-related adverse effect (97.9% in the abemaciclib group and 86.1% in the standard care group). The most frequent adverse effects were diarrhea, neutropenia, and fatigue in the abemaciclib group and arthralgia, hot flushes, and fatigue in the standard care group. There was a 16.6% treatment discontinuation rate in the abemaciclib arm.

Additional translational studies will help identify who is most likely to benefit from the addition of this therapy; longer follow-up will help determine whether the use of adjuvant abemaciclib will improve overall survival. However, these early findings are encouraging and represent the first treatment advance in 20 years in the adjuvant setting for this form of breast cancer.

Combination offers chemotherapy-free alternative first-line treatment for patients with advanced non–small-cell lung cancer. 
Over the past two decades, treatment has improved for non–small-cell lung cancers (NSCLC) with certain identifiable driver mutations, and in the last 5 years, immune checkpoint inhibitors have further transformed the treatment outlook—especially for patients with cancers that do not harbor driver mutations. Checkpoint inhibitors help the immune system identify and target cancer cells. Nivolumab and ipilimumab target different but complementary immune checkpoints.57 Nivolumab targets programmed death-ligand 1 (PD-L1), a protein that can slow down the immune system’s ability to target some cancer cells, whereas ipilimumab acts on a different protein.

In the open-label phase III randomized CheckMate 227 study (ClinicalTrials.gov identifier: NCT02477826),58 investigators demonstrated the nivolumab-ipilimumab combination significantly improved overall survival compared with chemotherapy alone (17.1 v 14.9 months) in patients newly diagnosed with advanced NSCLC and with PD-L1 levels of at least 1% (PD-L1 positive). Median overall survival was also improved with the combination therapy in patients with a PD-L1 expression level of less than 1%— 17.2 months with nivolumab-ipilimumab compared with 12.2 months with chemotherapy alone. Treatment-related serious adverse events of any grade were more common with the combination immunotherapy regimen (24.5%) than with chemotherapy alone (13.9%). Treatment-related adverse events leading to discontinuation were also greater with the combination immunotherapy therapy (18.1%) than with chemotherapy (9.1%).

The combination therapy allows certain patients to avoid chemotherapy, which can significantly limit quality of life. In May 2020, the FDA approved this combination for the treatment of patients with advanced NSCLC with a PD-L1 expression of 1% or greater.

Rituximab plus chemotherapy improves survival for children with mature B-cell non-Hodgkin lymphoma.
Over the last 30 years, therapies have been refined for children and adolescents diagnosed with mature B-cell non-Hodgkin lymphoma (primarily Burkitt lymphoma or diffuse large B-cell lymphoma) and resulted in improved outcomes.59 However, treatment options are still limited for those patients with high-risk features (higher stage, elevated levels of the protein lactate dehydrogenase, and CNS involvement) or those with cancer that does not respond to initial therapy. Although the addition of rituximab to standard chemotherapy has been shown to be effective in adults, it has not been tested in children and adolescents.60 Rituximab destroys both normal and malignant B cells, and although effective in treating B-cell cancers, it carries the risk of serious adverse effects.61

Investigators conducted an open-label, randomized phase III study (ClinicalTrials.gov identifier: NCT01516580)62 including 328 children and adolescents 2-17 years with high-grade, high-risk, mature B-cell non-Hodgkin lymphoma. Initially, patients were randomly assigned to receive standard-of-care chemotherapy alone or with rituximab. Random assignment was stopped, however, after the first interim analysis because of the high efficacy of the rituximab chemotherapy combination, and all enrolled patients were allowed to receive the combination therapy. At 3 years, 93.9% of those who had received rituximab-chemotherapy and 82.3% in the chemotherapy-only group had no primary refractory disease, progression, relapse, a second cancer, or death from any cause. Overall survival at 3 years was also greater for those who received rituximab (95.1%) than those who received chemotherapy only (87.3%). However, patients who received rituximab experienced greater adverse effects, suggesting that longer-term monitoring, particularly for infectious complications, may be required. One-third of patients had infusion reactions during the first rituximab treatment, although this decreased with subsequent infusions. After the initial chemotherapy, grade 4 or greater adverse events were seen in the rituximab chemotherapy group (33.3%), compared with the chemotherapy-only group (24.2%). Grade 4 or greater neutropenia with fever and infection were both more common among patients who received rituximab.

Adding rituximab to chemotherapy has been adopted as the standard of care for patients with high-risk disease. This study was funded in part by NCI.

First new treatment for hepatocellular carcinoma approved in more than ten years.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death.63,64 When most patients with HCC initially seek care, they have tumors that cannot be removed surgically and have a poor prognosis.65 The targeted therapy sorafenib has been the mainstay of treatment for HCC that is inoperable, although adverse effects are common and often impair quality of life.66

In early trials, the combination of atezolizumab and bevacizumab showed antitumor activity against inoperable HCC and adverse effects were generally tolerable.67 Atezolizumab is a type of immunotherapy known as a PD-L1 inhibitor that helps the body’s immune system attack cancer cells.68 Bevacizumab is a vascular endothelial growth factor inhibitor that helps limit the blood supply to tumors.

Researchers confirmed the earlier findings of antitumor activity in the large, randomized phase III IMbrave150 trial (ClinicalTrials.gov identifier: NCT03434379),70 which included 501 patients not previously treated with systemic therapy. Patients were randomly assigned to receive either the atezolizumab-bevacizumab combination or sorafenib. Overall survival at 12 months was 67.2% for patients who received the combination compared with 54.6% for those in the sorafenib group. In addition, the estimated median time until the cancer progressed was 6.8 months for the combination treatment and 4.3 months for sorafenib alone. Serious adverse events were more common among patients who received atezolizumab plus bevacizumab—38% as compared with 30% with sorafenib. Grade 5 adverse events occurred in 4.6% of patients who received the combination compared with 5.8% with sorafenib.

The combination of atezolizumab and bevacizumab was approved by the FDA in May 2020 for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy.71 Inoperable HCC has been an area of great clinical need, and the approval marks the first immunotherapy combination to be approved for this cancer.

Drug combination extends survival in older patients with acute myeloid leukemia.
Acute myeloid leukemia (AML) can occur in people of any age, but the disease more commonly affects older individuals, with an average age of diagnosis of 68 years.72,73 Yet, older patients with cancer typically receive less aggressive treatment, often as a result of competing health issues or, in some cases, a lack of proven therapies.74 Azacitidine is a drug that blocks a protein that slows down cancer cell death.75 Early studies had suggested that adding venetoclax (a drug that works in a similar way) to azacitidine may improve survival over other available treatments.76

In the phase III VIALE-A trial (ClinicalTrials.gov identifier: NCT02993523), researchers compared the azacitidine-venetoclax combination with azacitidine and placebo77 among patients age 75 or older who had not received prior treatment and could not safely undergo intensive standard care. They found that overall survival was longer for patients who received the azacitidine-venetoclax combination (14.7 months) compared with those who received azacitidine and placebo (9.6 months). Serious side effects were common in both groups, occurring in 83% of patients who received the combination therapy and 73% who received azacitidine and placebo. Grade 3 or higher hematologic side effects included thrombocytopenia, neutropenia, and febrile neutropenia.

Based on these results, in October 2020 the FDA approved venetoclax in combination with azacitidine, or decitabine, or low-dose cytarabine in adults age 75 or older newly diagnosed with AML who are ineligible for intensive chemotherapy or who have comorbidities that preclude the use of intensive induction chemotherapy. This approval provides an important new effective treatment option for older patients with AML.

Targeted Therapies

Response to HER2-targeting antibody-drug conjugate seen in patients with lung cancer.
Trastuzumab deruxtecan has shown efficacy in the treatment of patients with breast cancer and gastric cancer that makes too much of a protein called HER2-positive (see Antibody-Drug Shows Promise in GI Cancers). The treatment has also shown promise for NSCLC. HER2 positivity has been recognized in lung adenocarcinoma for some time, occurring in about 2% of cases.78 However, trials of HER2 inhibitors to date have disappointed.

Data from the phase II DESTINY-Lung01 trial (ClinicalTrials.gov identifier: NCT03505710),79 which was presented in the virtual scientific program of the 2020 ASCO Annual Meeting, were more encouraging. In the data presented, 61.9% of pretreated patients with advanced HER2-positive NSCLC who received trastuzumab deruxtecan had a confirmed response. The time to disease progression was estimated to be 14 months. More than half (52.4%) of patients had treatment-related adverse events of grade 3 or greater, including decreased neutrophil count and anemia. Five patients developed drug-related interstitial lung disease. Although longer-term data are needed, trastuzumab deruxtecan represents the most promising treatment to date for this population of patients with lung cancer.

Postsurgery targeted therapy doubles disease-free survival in early, EGFR-positive non–small-cell lung cancer.
Platinum-based chemotherapy following surgery has been the recommended treatment for patients with stage II-IIIA NSCLC, although this treatment only reduces the risk of recurrence or death by around 16% compared with surgery alone.80,81 Data from the phase III ADAURA trial (ClinicalTrials.gov identifier: NCT02511106)82 offer a promising new option for patients with tumors that have a mutated epidermal growth factor receptor gene (EGFR). The trial found that giving the EGFR-targeted drug osimertinib after surgery with or without platinum-based chemotherapy at the clinician’s discretion improved 24month disease-free survival (the time from treatment to either disease return or death) to about 90%, compared to 44% among patients who received the same surgery and chemotherapy regimen plus placebo. In fact, the trial was unblinded early after this dramatic improvement. Of patients with stage II-IIIA NSCLC receiving osimertinib after surgery, the risk of disease recurrence or death was reduced by 83%.

The improvement in disease-free survival seen in this study strongly supports the use of this targeted therapy in earlier stage disease and is practice-changing for resected, early-stage, EGFR-mutation-positive NSCLC.

Targeted therapy prompts response in patients with NSCLC carrying specific mutation.
It is estimated that 1%-2% of patients with NSCLC carry a type of genetic mutation called RET fusion, which is involved in the production of abnormal proteins that promote the growth of cancer cells.83 Selpercatinib is a targeted therapy that works to block these proteins. In the phase I-II LIBRETTO-001 trial (ClinicalTrials.gov identifier: NCT03157128),84 researchers evaluated the efficacy and safety of the drug in patients with RET fusion–positive NSCLC who had previously received platinum-based chemotherapy (49 patients) and also those who were previously untreated (39 patients). Across both patient groups, researchers observed high, long-lasting responses. Of patients who had received previous treatment, 64% had an objective response, defined as complete or partial response, or disease that did not progress; responses lasted for a median of 17.5 months. Among patients who had not previously been treated, 85% had a response; 90% of these patients continued to respond at 6 months of follow-up. Grade 3 or 4 hypertension was the most common adverse event. Six grade 5 adverse events were observed, although these were not determined to be related to selpercatinib. Overall, treatment-related adverse events did not require dose interruption or modification. Although larger trials are needed to confirm these findings, the efficacy of selpercatinib combined with its safety holds promise for patients with NSCLC that harbors RET fusion alterations. The FDA approved selpercatinib for the treatment of adult patients with metastatic RET fusion–positive NSCLC in May 2020.85

Photo of Xin Zheng and her husband, Zhigang Wei, PhD “All patients should have access to genomic sequencing and to clinical trials. I would not be here today if I had not been privy to advancements in precision oncology. I want every person with cancer to have that same opportunity to live with their cancer and not die of it.”

—Xin Zheng (pictured left with husband, Zhigang Wei, PhD), is a survivor of non-small–cell lung cancer.

Excerpted from an article in The ASCO Post in which she writes about her experience with clinical cancer trials.

PARP inhibitor doubles progression-free survival for men with hormone therapy-resistant prostate cancer.
Metastatic prostate cancer that grows and continues to spread despite hormone therapy is often referred to as metastatic castration-resistant prostate cancer (mCRPC). Although there have been significant therapeutic developments in this setting, it remains an incurable disease.86 Recent evidence demonstrates that about a third of patients with mCRPC harbor specific gene mutations that inhibit the repair of DNA damage, with the most prominent of these being mutations in BRCA 1/2 and ATM. Data suggest that men with these gene mutations may benefit from treatment with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, such as olaparib and rucaparib.87-89

The phase III PROfound trial (ClinicalTrials.gov identifier: NCT02987543)90 examined the efficacy and safety of olaparib. Patients with mCRPCwith at least one alteration in BRCA 1, BRCA 2,or ATM were randomly assigned 2:1 to receive olaparib (162 patients) or the treating clinician’s choice of enzalutamide or abiraterone (83 patients). At the time of data cutoff, the median time to disease progression was twice as long for patients receiving olaparib (7.4 months) compared with those receiving enzalutamide/ abiraterone (3.6 months). The median overall survival was significantly longer in the olaparib group (19.1 months) than in those receiving enzalutamide or abiraterone (14.7 months). There were more grade 3 and 4 events in the olaparib arm with the most common toxicities being anemia, nausea, fatigue, and loss of strength.

Based on data from the PROfound trial, in May 2020 the FDA approved olaparib for mCRPC with mutations in certain genes involved in DNA repair, in disease that has progressed following prior treatment with enzalutamide or abiraterone.91

Targeted therapy improves survival and symptoms in lung cancers that spread to CNS.
Leptomeninges are part of the inner layers of the tissue surrounding the brain and spinal cord, which protect the CNS. Although metastasis to the leptomeninges is not common in patients with advanced lung cancer (3%-4%), the incidence of leptomeningeal metastasis is greatest (9%) among patients with EGFRm NSCLC.92,93

A phase I trial, the BLOOM study (ClinicalTrials.gov identifier: NCT02228369) showed dramatic reductions in leptomeningeal metastases and related symptoms among patients with EGFRm NSCLCs with the use of osimertinib, a drug that targets a specific mutation in EGFR.94 Inadisease state where median overall survival has traditionally been measured in weeks, median overall survival for the 41 patients in the trial was 11 months. Median progression-free survival was 8.6 months. In addition, over half of the patients who had neurologic symptoms at baseline (57%) improved with treatment. Adverse events and tolerability of osimertinib were similar to those that typically accompany treatment with the drug. The most common adverse events of any grade were rash or acne, diarrhea, and nausea.

Other Therapies

Maintenance immunotherapy following chemotherapy extends survival for patients with advanced urothelial cancer. 
The introduction of immunotherapies—including checkpoint inhibitors—over the last several years has improved the care of patients with metastatic urothelial cancer. Checkpoint inhibitors target the proteins PD-1 or PD-L1, blocking cancer cells from turning off the immune system.

In the JAVELIN Bladder 100 trial (ClinicalTrials.gov identifier: NCT02603432),95 researchers explored the addition of the PD-L1 inhibitor avelumab to best supportive care in patients with metastatic urothelial cancer that was stable or had responded to platinum-based chemotherapy. The researchers found that maintenance therapy with avelumab extended overall survival (21.4 months) compared with best supportive care alone (14.3 months). Best supportive care is aimed at improving quality of life for patients. Adverse events of grade 3 or higher occurred more frequently (47.4%) in patients who received avelumab compared with those who did not (25.2%).

The study results represent the largest survival benefit seen in advanced urothelial cancer following chemotherapy.

Improved survival with androgen receptor inhibitors in castration-resistant prostate cancer. 
Initial evidence from phase III trials demonstrated that three novel androgen receptor inhibitors—enzalutamide, apalutamide, and darolutamide—could improve metastases-free survival in patients who have castration-resistant prostate cancer and certain biomarkers.96,97 However, an overall survival benefit has not yet been seen.98,99

The phase III PROSPER trial (ClinicalTrials.gov identifier: NCT02003924)100 of nearly 1,400 patients showed that adding enzalutamide to hormone therapy more than doubled metastases-free survival (36.6 months) in this population of patients compared with hormone therapy alone (14.7 months). Long-term data from this study showed an overall survival benefit with enzalutamide (67 months) compared with hormone therapy alone (56.3 months). Results from two other large phase III studies produced similar findings with the use of apalutamide and darolutamide compared with hormone therapy alone. Overall survival with apalutamide was longer (73.9 months) compared with hormone therapy alone (59.9 months). Three-year overall survival was longer with darolutamide (83%) compared to hormone therapy only (77%).101,102

These findings can help guide treatment discussions between doctors and patients with nonmetastatic castration-resistant prostate cancer.

Adding local radiotherapy to standard chemotherapy boosts survival for nasopharyngeal carcinoma.
Although nasopharyngeal carcinoma (cancer located behind the nose and above the back of the throat) is not common in the United States, it occurs frequently in Southeast Asian and native Alaskan populations.103 For patients with metastatic disease, chemotherapy using gemcitabine and cisplatin is the standard of care as first-line treatment.104 The use of local therapy, however, has proven beneficial in two previous randomized clinical trials involving this type of cancer.105,106

Researchers administered local radiotherapy to patients with newly diagnosed metastatic nasopharyngeal carcinoma to determine if survival could be improved. In the study (ClinicalTrials.gov identifier: NCT02111460),107 63 patients were randomly assigned to undergo local or regional radiation treatment in addition to chemotherapy with cisplatin and fluorouracil while 63 received chemotherapy alone. Overall survival at 24 months was significantly longer for the group that received localized radiation (76.4%) compared with those on chemotherapy alone (54.5%). Radiotherapy was associated with grade 3 or higher dermatitis, mucositis, and xerostomia. Harmful adverse effects in the blood, liver, kidneys, and GI tract were comparable between the groups. These results improve standard treatment for metastatic nasopharyngeal carcinoma and add to a growing body of data demonstrating local therapies can play an important role in the treatment of metastatic cancer.

First-in-class drug reduces transfusion dependence in patients with lower-risk myelodysplastic syndromes. 
Myelodysplastic syndromes (MDS) are a group of cancers in which patients’ bone marrow produces too few healthy blood cells. One of the most common signs of MDS is anemia.108 Patients with lower-risk MDS who are anemic are typically treated with red blood cell (RBC) transfusions and erythropoietin-stimulating agents; however, not all patients are able to tolerate these therapies. Some patients may develop side effects that are difficult to tolerate, limiting the use of these medicines. Some patients who are unable to tolerate these side effects can require repeated transfusions to replace red blood cells, which can affect quality of life and carry risk as well. Patients with low-risk disease (disease unlikely to progress to acute leukemia) can require transfusions for long periods of time. Therefore, there is a significant need for new treatments that can improve anemia.109-112 

Luspatercept is a new type of drug that helps RBC precursors become red blood cells, thereby increasing the RBC count.113 The phase III MEDALIST trial (ClinicalTrials.gov identifier: NCT02631070) evaluated the efficacy and safety of luspatercept in patients with lower-risk MDS with ring sideroblasts (faulty RBC precursors), who had been receiving regular RBC transfusions and had disease that was refractory or unlikely to respond to erythropoiesis-stimulating drugs, or who experienced side effects causing them to discontinue treatment.114 Patients were randomly assigned to receive luspatercept (153 patients) or placebo (76 patients). More patients in the luspatercept arm (38%) no longer required transfusions (the study’s primary endpoint) for 8 weeks compared with those in the placebo arm (13%). Grade 3 or 4 serious adverse events were comparable in the two groups, seen in 42% of those receiving luspatercept and in 45% receiving placebo. The findings of this trial led to the approval of luspatercept by the FDA for lower-risk myelodysplastic syndromes with ringed sideroblasts.115

CAR T cell treatment improves survival for majority of patients with relapsed or refractory mantle cell lymphomas, established as new treatment option.
Mantle cell lymphoma is an aggressive type of B-cell non-Hodgkin lymphoma and is generally considered incurable without an allogeneic stem-cell transplant. Standard therapy with chemoimmunotherapeutic regimens, particularly using certain targeted drugs (BTK inhibitors), has led to a significant survival improvement for patients with relapsed or refractory disease.116,117 However, patients with cancer that has progressed further typically have poor survival (less than 12 months).118

KTE-X19 is a chimeric antigen receptor (CAR) T cell treatment. CAR T cells are immune cells collected from a patient’s blood that are genetically altered to better target cancer cells and then infused back into the patient as a one-time treatment.119 KTE-X19 targets the CD19 antigen found on the surface of B cells, which are commonly associated with mantle cell lymphoma.

In the phase II ZUMA-2 trial (ClinicalTrials.gov identifier: NCT02601313),120 patients with relapsed and/or refractory disease who had undergone up to five previous treatments, including BTK inhibitors, were treated with KTE-X19. Responses were observed in 85% of the 60 patients included in the analysis, and 59% had a complete response. At a median of 12.3 months of follow-up, 57% of patients were in remission. At 12 months, progression-free survival was 61%, and overall survival 83%. The toxicity profile was similar to that of other CAR T therapies, including grade 3 or higher cytokine release syndrome and neurologic events in 15% and 31% of patients, respectively. None of these was fatal.

Based on these results, the FDA granted accelerated approval to KTE-X19 (brexucabtagene autoleucel) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma.121 This marks the third FDA-approved CAR T therapy and the first for patients with advanced mantle cell lymphoma.

Headshot of Dr. Lidia Schapira“The most important thing for patients considering joining a clinical trial is to be well informed, to take the time to review options, and to discuss these findings with loved ones. As oncologists, we want to make sure that each patient feels they are making the right choice for them about treatment.”

—Lidia Schapira, MD, FASCO, is the Cancer.Net Editor in Chief, an Associate Professor of Medicine at Stanford University School of Medicine, and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute.

Excerpted from an article on Cancer.Net in which Dr. Schapira discusses the importance of clinical trials in treating people with cancer.

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