Plain language summary of zanubrutinib or ibrutinib in chronic lymphocytic leukemia that is resistant to treatment or has come back after treatment.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a research study called ALPINE. The study involved people who had been diagnosed with, and previously treated at least once for, relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Lymphocytes help to find and fight off viruses and infections in the body, but when someone has CLL or SLL, the body creates abnormal lymphocytes, leaving the patient with a weakened immune system and susceptible to illness. In CLL, these lymphocytes are in the bone marrow and bloodstream, whereas for SLL, they are mostly found in the lymph nodes, such as those in the neck. HOW WAS THE RESEARCH DONE?: The ALPINE study was designed to directly compare the cancer-fighting effects and side effects of zanubrutinib and ibrutinib as treatment for patients with relapsed or refractory CLL/SLL. WHAT WERE THE RESULTS?: After 30 months, zanubrutinib was more effective than ibrutinib at reducing and keeping the cancer from coming back. Clinical Trial Registration: NCT03734016 (ClinicalTrials.gov).

Plain language review: what are biosimilar medicines and how can they be used to treat people with cancer?

WHAT IS THIS SUMMARY ABOUT?: The aim of this plain language review article is to help you to understand biosimilar medicines (called biosimilars) by giving a summary of biologic medicines and biosimilars. It is based on the experience of an international panel of physicians with expertise on biosimilars who discussed and agreed on the topics and information included in this review article. Biologic medicines are medicines that come from living organisms such as bacteria and animal or plant cells. Biosimilars are a group of approved biologic medicines that are similar to original biologic medicines that are already available. This review explains how biosimilars are developed and approved, and how they are used to treat people with cancer. It also answers some common important questions people with cancer might have when taking biosimilars. The purpose of this plain language review is to help you to understand the findings from recent research. This review reports information from peer-reviewed literature and other sources available in the public domain (e.g., regulatory documents or product information labels). The findings may differ from those of other review articles. Health professionals should make treatment decisions based on all available evidence.

Treatment of the blood cancer polycythemia vera with ruxolitinib in the MAJIC-PV study: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article describing the main results of the MAJIC-PV study. This study looked at using the cancer drug ruxolitinib to treat a type of blood cancer called polycythemia vera. People with polycythemia vera make too many red blood cells in their body. This can make their blood thicker and can increase the chances of blood clots forming in their blood vessels.Researchers wanted to find out how well ruxolitinib worked compared with the best available therapy as a treatment for people with polycythemia vera who were at risk of developing blood clots that could lead to a heart attack or stroke. Specifically, the study looked at people who had already taken the chemotherapy hydroxycarbamide (also known as hydroxyurea) for their polycythemia vera, but it either didn't work for them or gave them side effects that they could not tolerate. WHAT WERE THE RESULTS?: In the study, researchers divided 180 adults with polycythemia vera who were at high risk of developing blood clots that could lead to a stroke into two groups: 93 people who took ruxolitinib twice a day, and 87 people who took the best available therapy. 43% of people who took ruxolitinib and 26% of people who had the best available therapy had normal blood counts and spleen size within 1 year of treatment. 84% of people who took ruxolitinib and 75% of people who had the best available therapy lived for at least 3 years without their polycythemia vera becoming a more advanced type of blood cancer. The most common side effects were disorders of the digestive system (stomach and gut), disorders of the blood vessels, and infections. This is similar to the side effects that doctors know about for ruxolitinib. WHAT DO THE RESULTS MEAN?: Compared with people who had the best available therapy for their polycythemia vera, people who took ruxolitinib were more likely to have normal blood counts and spleen size within 1 year of treatment, and were more likely to live longer without their polycythemia vera becoming a more advanced type of blood cancer.

A plain language summary of the PERSEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for treating newly diagnosed multiple myeloma.

What is this summary about?: This summary describes the first analysis of the PERSEUS study, which looked at adults with multiple myeloma that had never been treated before, also called newly diagnosed multiple myeloma. Multiple myeloma is a type of cancer in the blood, specifically in plasma cells within the soft, spongy tissue in the center of most bones, called the bone marrow. Researchers wanted to see if adding daratumumab (D) to a standard treatment of three other medicines called VRd, which stands for bortezomib (V), lenalidomide (R), and dexamethasone (d), could stop the multiple myeloma from getting worse and help participants live longer without multiple myeloma. Half of the participants were assigned to the treatment plan with daratumumab; they received D-VRd during initial treatment phases (induction and consolidation), followed by daratumumab as well as lenalidomide (D-R) in the maintenance phase. The other half of participants received treatment without daratumumab; they received VRd induction and consolidation followed by lenalidomide alone (R) maintenance. In addition, all participants were able to receive an autologous stem cell transplant, a procedure used to further help reduce multiple myeloma. What were the results?: At the time of this analysis of PERSEUS, about 4 years after participants started the study, participants who received D-VRd treatment followed by D-R maintenance had a better response to treatment (as measured by specific markers of multiple myeloma) and were more likely to be alive and free from their multiple myeloma getting worse in comparison to participants who received VRd followed by R maintenance. Side effects (unwanted or undesirable effects of treatment) in both treatment groups were in line with the known side effects of daratumumab and VRd. What do the results mean?: The results of the PERSEUS study showed that including daratumumab in D-VRd induction/consolidation and D-R maintenance was better for treating multiple myeloma than the current standard VRd treatment followed by R maintenance alone in adults with a new diagnosis of multiple myeloma who were also able to receive an autologous stem cell transplant. Of importance, there were no unexpected side effects in either group. Clinical Trial Registration: NCT02874742 (GRIFFIN) (ClinicalTrials.gov).^ieng

The effects of adding palbociclib to endocrine therapy to treat advanced breast cancer: a plain language summary of a study using the PALOMA-2 and PALOMA-3 trial results.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article that reported results of a study using data from two phase 3 clinical trials called "PALOMA-2" and "PALOMA-3." Both PALOMA-2 and PALOMA-3 trials included women with HR+/HER2- advanced breast cancer. HR+/HER2- breast cancer means the breast cancer cells of these women have receptors for female sex hormones and little or no HER2 receptors. Both PALOMA trials tested the effect of adding a medication called palbociclib (brand name, Ibrance®) to a hormone therapy. Hormone therapy, also known as endocrine therapy, is a treatment that blocks or removes hormones that cause cancer cells to grow and divide. In both trials, women took endocrine therapy with either palbociclib or a placebo. WHAT WAS THE AIM OF THIS STUDY?: The researchers aimed to see if the results from the PALOMA trials were similar for subgroups of women in the 2 trials. The subgroups in the study included women who shared certain features about their cancer or treatment history, for example, women whose cancer had spread to the liver. For each subgroup, the study compared the results from the 2 treatment groups: (1) women who took palbociclib plus endocrine therapy, and (2) women who took placebo plus endocrine therapy. WHAT WERE THE RESULTS & WHAT DO THEY MEAN?: The same effect was found in all subgroups. Compared with those who took placebo, women who took palbociclib lived longer without their cancer getting worse (growing or spreading). Also, among women who had chemotherapy after stopping the trial treatment, those who took palbociclib started chemotherapy later than those who took placebo. Because palbociclib slows cancer growth and leads to tumor shrinkage, this may have played a part in starting chemotherapy later. These results show that palbociclib plus endocrine therapy is better at slowing the progression of advanced HR+/HER2- breast cancer than endocrine therapy alone. This can be said for women with different advanced HR+/HER2- breast cancer features and treatment history. Overall, the results support women taking palbociclib with an endocrine therapy if they have advanced HR+/HER2- breast cancer.

Plain language summary of erdafitinib in locally advanced or metastatic urothelial carcinoma: a phase 2 study with long-term follow-up.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of two articles describing the results from a study called BLC2001. The study examined the effect of a medication called erdafitinib on participants with a type of cancer known as urothelial carcinoma that had either spread beyond the bladder or urinary tract into surrounding organs and/or nearby muscles (locally advanced) and was not removable by surgery (unresectable) or had spread to other parts of the body (metastatic). In this study, researchers wanted to learn if erdafitinib was safe and effective at stopping or reducing tumor growth in participants with locally advanced and unresectable or metastatic urothelial carcinoma with certain genetic alterations (changes in DNA sequence) in two related genes called fibroblast growth factor receptor 2 (FGFR2) and 3 (FGFR3). Treatment options for people with this disease are very limited; some may not have responded to other therapies, or their tumors continued to grow after they received other treatments. 212 participants took part in the study. 111 participants were treated with oral (by mouth) erdafitinib at different doses to find a recommended dose regimen. 101 additional participants then received the recommended starting dose of erdafitinib at 8 mg daily with possible increase to 9 mg daily, these participants make up the 8 mg regimen group. WHAT WERE THE RESULTS OF THE BLC2001 STUDY IN THE 8 MG REGIMEN GROUP?: Researchers found that tumors decreased in size or completely disappeared in 40% of participants. With approximately 1 year of follow-up, an estimated 55% of participants were still alive, and after 2 years, an estimated 31% of participants were still alive. Common side effects of erdafitinib included high phosphate levels in the blood (hyperphosphatemia), an inflamed and sore mouth, diarrhea, and dry mouth. WHAT DO THE RESULTS MEAN?: Participants had locally advanced and unresectable or metastatic urothelial carcinoma with certain FGFR gene alterations that had been treated with erdafitinib after previous chemotherapy and/or a type of medicine that uses the immune system to help the body fight cancer (immunotherapy). The BLC2001 study found that some participants treated with 8 mg erdafitinib had the benefit of a longer period without their cancer growing or spreading to other parts of the body. About 80% of participants achieved some level of disease control where their tumor shrank or remained stable.

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab.

WHAT IS THIS SUMMARY ABOUT?: This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder. WHAT WERE THE RESULTS?: In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects. Within about 2 months of starting treatment, most patients' (73%) tumors were smaller and stayed smaller, on average, for more than 2 years. WHAT DO THE RESULTS MEAN?: The combination of enfortumab vedotin plus pembrolizumab is a new treatment option for patients with locally advanced or metastatic urothelial cancer when they cannot receive the typical treatment, cisplatin. Advanced or metastatic urothelial cancer is a type of cancer where the cancer has already spread outside of the bladder or urinary tract.

Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: a plain language summary of the monarchE study.

WHAT IS THIS SUMMARY ABOUT?: This article summarizes the most recent results of the monarchE study. This study was completed in participants with a type of breast cancer called HR+, HER2-, node-positive, high-risk early breast cancer. In this study, abemaciclib, a non-chemotherapy treatment, was administered with standard of care endocrine therapy after curative surgery. Most participants had received prior chemotherapy and/or radiotherapy. The study investigated if abemaciclib helped participants live longer without their cancer returning compared with participants who only received standard of care endocrine therapy. The study participants were assigned to 1 of 2 treatment groups. Participants in Group A were assigned to receive standard of care endocrine therapy with abemaciclib for 2 years, followed by endocrine therapy for a total of at least 5 years. Participants in Group B were assigned to receive standard of care endocrine therapy only for at least 5 years. The effect of treatment was compared between these 2 groups. WHAT WERE THE RESULTS?: Overall, the results showed that the cancer was 34% less likely to come back after surgery in the participants in Group A (abemaciclib plus endocrine therapy) compared with those in Group B (endocrine therapy only). At 4 years since the start of the study treatment, more participants who received the combination of abemaciclib plus endocrine therapy remained free of cancer compared with participants who received endocrine therapy alone (86% versus 79%). Participants who received abemaciclib plus endocrine therapy had more side effects than those who received endocrine therapy alone, but most of these effects were mild to moderate and reversible upon the end of therapy. The most common side effects in the abemaciclib group were diarrhea, infections, low number of white blood cells, and tiredness. WHAT DO THE RESULTS MEAN?: This study found that administering abemaciclib in combination with standard endocrine therapy after curative breast surgery helped lower the risk of cancer returning in people with HR+, HER2-, node-positive, high-risk early breast cancer. Abemaciclib is a new treatment option for people with this diagnosis. People with high-risk early breast cancer should always talk to their doctors and nurses before making any decisions about their treatment.Clinical Trial Registration: NCT03155997 (monarchE study).

Treatment outcomes in older patients with metastatic breast cancer receiving palbociclib plus an aromatase inhibitor: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone. HOW WAS THE STUDY IN THIS SUMMARY CARRIED OUT?: The Flatiron database contains medical records for people with cancer in the US. This study used deidentified health care information from this database. 'Deidentified' means that all information that could identify an individual was removed to protect individuals' privacy. People in this study received treatment in routine care and not in a clinical trial. WHAT DO THE RESULTS MEAN?: Older patients who took palbociclib plus an aromatase inhibitor lived longer than those who took an aromatase inhibitor alone. Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

This study evaluated outcomes in elderly patients with metastatic breast cancer treated in routine care. Overall, patients who took palbociclib plus an aromatase inhibitor (AI) lived longer, and lived longer without their cancer getting worse, than those who took an AI alone.

Plain language summary of the CheckMate 76K study results: nivolumab given after stage 2B/2C melanoma is removed by surgery.

WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in Nature Medicine in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells. In melanoma, staging describes the severity of the cancer. Melanoma staging ranges from 0 (very thin and confined to the upper layer of the skin) to 4 (spread to distant parts of the body), with earlier stages removed by surgery. The people in this study had stage 2 melanoma that had not spread to the lymph nodes or other organs in the body. HOW WAS THE STUDY DESIGNED?: People 12 years and older with stage 2 melanoma that had not spread and had been removed by surgery were included in CheckMate 76K. People were randomly assigned to receive either nivolumab (526 patients) or placebo (264 patients). A placebo resembles the test medicine but does not contain any active medicines. The researchers assessed whether people who received nivolumab lived longer without their cancer returning and/or spreading to other parts of their bodies (compared with placebo) and if nivolumab was well tolerated. WHAT WERE THE RESULTS?: Researchers found that people who received nivolumab were 58% less likely to have their cancer return and 53% less likely of having their cancer spread to distant parts of their body, compared with placebo. These reductions in risk with nivolumab were seen in different subgroups of people with a range of characteristics, and regardless of how deep the melanoma had gone into the skin. People taking nivolumab had more side effects than those taking placebo, but most were mild to moderate and manageable. WHAT DO THE RESULTS MEAN?: Results from CheckMate 76K support the benefit of using nivolumab as a treatment option for people with stage 2 melanoma post-surgery.

A plain language summary of the PHAROS study: the combination of encorafenib and binimetinib for people with BRAF V600E-mutant metastatic non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of the results of a study called PHAROS. This study looked at combination treatment with encorafenib (BRAFTOVI®) and binimetinib (MEKTOVI®). This combination of medicines was studied in people with metastatic non-small-cell lung cancer (NSCLC). NSCLC is the most common type of lung cancer. Metastatic means that the cancer has spread to other parts of the body. All people in this study had a type of NSCLC that has a change in a gene called BRAF termed a BRAF V600E mutation. A gene is a part of the DNA that has instructions for making things that your body needs to work, and the BRAF V600E mutation contributes to the growth of the lung cancer. WHAT WERE THE RESULTS?: In this study, 98 people with BRAF V600E-mutant metastatic NSCLC were treated with the combination of encorafenib and binimetinib (called encorafenib plus binimetinib in this summary). Before starting the study, 59 people had not received any treatment for their metastatic NSCLC, and 39 people had received previous anticancer treatment. At the time of this analysis, 44 (75%) out of 59 people who did not receive any treatment before taking encorafenib plus binimetinib had their tumors shrink or disappear. Eighteen (46%) out of 39 people who had received treatment before starting encorafenib plus binimetinib also had their tumors shrink or disappear. The most common side effects of encorafenib plus binimetinib were nausea, diarrhea, fatigue, and vomiting. WHAT DO THE RESULTS MEAN?: These results support the use of encorafenib plus binimetinib combination treatment as a new treatment option in people with BRAF V600E-mutant metastatic NSCLC. The side effects of encorafenib plus binimetinib in this study were similar to the side effects seen with encorafenib plus binimetinib in people with a type of skin cancer called metastatic melanoma.

Plain language summary: 5-year results from the CROWN study of lorlatinib vs crizotinib in non-small-cell lung cancer.

WHAT IS THIS STUDY ABOUT?: This is a summary of the results of an ongoing study called CROWN. In the CROWN study, researchers looked at the effects of two medicines called lorlatinib (Lorbrena) and crizotinib (Xalkori) for people with advanced non-small cell lung cancer (NSCLC) who had not been treated yet. Everyone in the study had changes in a gene called anaplastic lymphoma kinase, or ALK, in their cancer cells. The changes in the ALK gene can make cancer grow. This analysis looked at how well lorlatinib and crizotinib worked and their side effects in people with advanced ALK-positive NSCLC after 5 years. WHAT DID THIS STUDY FIND?: After observing people for an average of 5 years, researchers found that more people who took lorlatinib were still alive without their cancer getting worse than the people who took crizotinib. At 5 years, the probability of being alive without their cancer getting worse was 60% in people who took lorlatinib compared with 8% in people who took crizotinib. Fewer people who took lorlatinib had their cancer spread within or to the brain than the people who took crizotinib. In more than half of the people who took lorlatinib, tumors that had spread to the brain did not get worse, and no new tumors spread to the brain after 5 years. In contrast, in about half of the people who took crizotinib, tumors that had spread to the brain got worse or new tumors spread to the brain after 16.4 months. More people who took lorlatinib (115 out of 149, or 77%) had severe or life-threatening side effects than people who took crizotinib (81 out of 142, or 57%). These side effects were like the ones reported in the earlier 3-year analysis. WHAT DO THE FINDINGS OF THE STUDY MEAN?: The 5-year results from the CROWN study showed that more people who took lorlatinib continued to benefit from their treatment than those who took crizotinib. The 5-year benefit of lorlatinib in people with ALK-positive NSCLC has never been seen before.Clinical Trial Registration: NCT03052608 (Phase 3 CROWN study) (ClinicalTrials.gov).

Treatment options for biliary tract cancer: unmet needs, new targets and opportunities from both physicians' and patients' perspectives.

Biliary tract cancer (BTC) is a rare cancer with poor prognosis, characterized by considerable pathophysiological and molecular heterogeneity. While this makes it difficult to treat, it also provides targeted therapy opportunities. Current standard-of-care is chemotherapy ± immunotherapy, but several targeted agents have recently been approved. The current investigational landscape in BTC emphasizes the importance of biomarker testing at diagnosis. MDM2/MDMX are important negative regulators of the tumor suppressor p53 and provide an additional target in BTC (∼5-8% of tumors are MDM2-amplified). Brigimadlin (BI 907828) is a highly potent MDM2-p53 antagonist that has shown antitumor activity in preclinical studies and promising results in early clinical trials; enrollment is ongoing in a potential registrational trial for patients with BTC.

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Pralsetinib in patients with RET fusion-positive non-small-cell lung cancer: A plain language summary of the ARROW study.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research study called ARROW, which tested a medicine called pralsetinib in patients with non-small cell lung cancer (NSCLC), thyroid cancer, and other advanced solid tumours caused by a change in a gene called RET. For the purposes of this summary, only patients with NSCLC with a change in RET called fusion (RET fusion+) are highlighted. WHAT WERE THE RESULTS?: In total, 281 patients with RET fusion+ NSCLC had taken part in this study across the USA, Europe, and Asia. Patients were asked to take four pills (adding up to 400 mg) of pralsetinib each day and were checked for any changes in their tumours, as well as for any side effects. After an average of 8 months of treatment with pralsetinib, 72% of previously untreated patients and 59% of patients who had previously received chemotherapy had considerable shrinkage of their tumours. Among 10 patients with tumours which had spread to the brain (all of whom had received previous treatments), 70% had their tumours shrink greatly in the brain after treatment with pralsetinib. On average, patients lived with little to no tumour growth for 16 months. In previously untreated patients, the most common severe side effects that were considered related to pralsetinib treatment were decreased white blood cells (neutrophils and lymphocytes), increased blood pressure, and an increase in a blood protein called creatine phosphokinase. In previously treated patients, the severe side effects were decreased white blood cells (neutrophils, lymphocytes, and leukocytes), increased blood pressure, and low levels of red blood cells. In both untreated and previously treated patients, the most common severe side effects that required hospital attention were lung inflammation/swelling causing shortness of breath (pneumonitis) and lung infection (pneumonia). WHAT DO THE RESULTS MEAN?: Overall, the ARROW study showed that pralsetinib was effective in shrinking tumours in patients with RET fusion+ NSCLC regardless of previous treatment history. The recorded side effects were expected in patients receiving this type of medicine. Clinical Trial Registration: NCT03037385 (ARROW) (ClinicalTrials.gov).

Enzalutamide in metastatic hormone-sensitive prostate cancer: A plain language summary of the ARCHES and ENZAMET follow-up studies.

WHAT IS THIS SUMMARY ABOUT?: This summary includes information from the ARCHES and ENZAMET follow-up studies. Both studies looked at enzalutamide treatment for people with metastatic hormone-sensitive prostate cancer (known as mHSPC). In ARCHES, researchers compared the medications enzalutamide + androgen deprivation therapy (known as ADT) with placebo + ADT. In ENZAMET, researchers compared enzalutamide + ADT with standard treatment + ADT. Some people in ENZAMET also took enzalutamide with docetaxel (a chemotherapy treatment). In both studies, researchers wanted to find out if enzalutamide helps people with mHSPC live longer. WHAT ARE THE KEY TAKEAWAYS?: In both studies, researchers found that people with mHSPC who took enzalutamide lived longer than people who did not. People who took enzalutamide also lived longer without their cancer getting worse. The results were mostly similar in groups of people dependingon when and where their cancer was found. Researchers did not find any new safety concerns. WHAT WERE THE MAIN CONCLUSIONS?: People with mHSPC may benefit from long-term treatment with enzalutamide + ADT. They may also benefit from taking enzalutamide with other treatments, like docetaxel. It may be better for people with mHSPC to have enzalutamide treatment before their cancer gets worse, rather than waiting. These people and their doctors should carefully consider the benefits and risks of each treatment to make a joint decision for treating mHSPC.Clinical Trial Registration: NCT02677896 (ARCHES), NCT02446405 (ENZAMET) (ClinicalTrials.gov).

Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of two articles. The first article is about a clinical trial called SPOTLIGHT and it was published in the medical journal The Lancet in in April of 2023. The second article is about a clinical trial called GLOW and it was published in the medical journal Nature Medicine in July of 2023. WHAT ARE THE KEY TAKEAWAYS?: Until recently, chemotherapy was the first treatment given to people with stomach cancer or gastroesophageal junction (or GEJ) cancer that is locally advanced unresectable or metastatic. When cancer cells have high amounts of the protein CLDN18.2 but do not have high amounts of the protein HER2, the cancer is known as CLDN18.2-positive (or CLDN18.2+) and HER2-negative (or HER2-). New medicines to treat cancer are being developed. These medicines attach to proteins on cancer cells to help the body recognize and kill cancer cells.The clinical trials SPOTLIGHT and GLOW included participants with CLDN18.2+ and HER2- stomach or GEJ cancer that was locally advanced unresectable or metastatic. These trials looked at whether adding a medicine called zolbetuximab to chemotherapy as the first treatment for cancer helped people live longer before their tumors grew bigger or new tumors grew, after starting the trial. These studies also looked at whether adding zolbetuximab to chemotherapy helped people live longer after starting the trial. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: In SPOTLIGHT and GLOW, on average, participants assigned to zolbetuximab plus chemotherapy lived 1.4 to 1.9 months longer before their tumors grew bigger or new tumors grew, after starting the trial, than participants assigned to a placebo plus chemotherapy. On average, participants assigned to zolbetuximab plus chemotherapy also lived 2.2 to 2.7 months longer, after starting the trial, than participants assigned to a placebo plus chemotherapy. These results suggest that zolbetuximab plus chemotherapy could be a new first treatment for people with CLDN18.2+ and HER2- stomach or GEJ cancer that is locally advanced unresectable or metastatic.Clinical Trial Registration: NCT03504397 (SPOTLIGHT); NCT03653507 (GLOW).

The clinical trials SPOTLIGHT and GLOW showed that, on average, participants with stomach or GEJ cancer assigned to zolbetuximab plus chemotherapy lived 2.2 to 2.7 months longer than participants assigned to a placebo plus chemotherapy.

Plain language summary of the CARTITUDE-4 study of ciltacabtagene autoleucel for the treatment of people with relapsed or refractory multiple myeloma.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a phase 3 clinical trial called CARTITUDE-4. This trial compared the anti-cancer therapy ciltacabtagene autoleucel (or cilta-cel) with standard therapies in people who have multiple myeloma, a cancer that affects specific kinds of blood cells called plasma cells. The people in the study had been treated with 1 to 3 previous treatments for multiple myeloma, including a common anti-myeloma treatment called lenalidomide, but their multiple myeloma did not get better. HOW WAS THE STUDY IN THIS SUMMARY CONDUCTED?: About half of the 419 participants in this study received cilta-cel, while the other half received standard therapies, or therapies that are commonly used to treat multiple myeloma. Participants who received cilta-cel had a type of immune cell called T cells collected from their blood and genetically modified to recognize a specific protein found on myeloma cells. These modified T cells, which comprise cilta-cel, were then infused back into the bloodstream. WHAT WERE THE RESULTS OF THE STUDY?: After approximately 1 year in the study, more participants were alive without their cancer getting worse in the cilta-cel group (76%) than in the standard therapies group (49%). The most common side effects in both groups were infections and low blood cell counts. Cytokine release syndrome (a potentially serious side effect caused by overactivation of the immune system) was common but mostly mild. Neurotoxicities (including immune effector cell-associated neurotoxicity syndrome, which can cause symptoms such as headaches, changes in consciousness, and difficulty with memory, attention, speaking, or understanding others) were less common and were reported in 20.5% of participants treated with cilta-cel. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: In CARTITUDE-4, more participants treated with cilta-cel showed improvements and were alive with control of their disease 12 months after receiving cilta-cel compared with participants who received standard therapies.Clinical Trial Registration: NCT04181827 (CARTITUDE-4) (ClinicalTrials.gov).

Prostate-specific antigen and health-related quality of life in individuals with advanced prostate cancer treated with apalutamide: a plain language summary of the SPARTAN and TITAN studies.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper that describes the results of the SPARTAN and TITAN studies, which looked at whether a treatment called apalutamide can help treat individuals with advanced prostate cancer.The SPARTAN study included 1207 participants with nonmetastatic castration-resistant prostate cancer (or nmCRPC). The TITAN study included 1052 participants with metastatic castration-sensitive prostate cancer (or mCSPC). Treatment with apalutamide was compared with treatment with placebo. In both studies, all participants were also given androgen deprivation therapy (or ADT), which has been used for many years for the treatment of prostate cancer.The results showed that treatment with apalutamide plus ADT increased participants' survival time while their health-related quality of life stayed the same, compared with placebo plus ADT. Also, apalutamide plus ADT increased the length of time that the cancer did not spread to other parts of the body (metastasize) or did not continue to grow. In both studies, treatment with apalutamide plus ADT was associated with a deep decline in blood prostate-specific antigen (or PSA) levels (called a deep PSA decline). This additional analysis of the SPARTAN and TITAN studies was performed to understand whether the deep PSA decline in participants who received apalutamide plus ADT was linked to their overall health-related quality of life. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, those who achieved a deep PSA decline after the start of treatment had a greater chance that their health-related quality of life would remain stable. When participants achieved a deep PSA decline at 3 months after the start of treatment, the benefit to their health-related quality of life, including physical wellbeing, was even greater. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH ADVANCED PROSTATE CANCER?: For individuals with advanced prostate cancer, it is important to monitor both PSA decline and any impacts on health-related quality of life. These results will help doctors and other healthcare professionals have a better understanding of patients' cancer experience and the impact of their treatment.Clinical Trial Registration: NCT01946204 (SPARTAN) and, NCT02489318 (TITAN) (ClinicalTrials.gov).

A plain language summary of the TROPiCS-02 study in patients with breast cancer (HR-positive/HER2-negative).

WHAT IS THIS SUMMARY ABOUT?: Sacituzumab govitecan (brand name: TRODELVY®) is a new treatment for certain types of advanced or metastatic breast cancer. One common type of breast cancer has at least 1 of 2 hormone receptors (HR positive) and does not have human epidermal growth factor 2 (HER2 negative). The HR and HER2 receptors are known to influence how severe a case of breast cancer is. Certain treatments will only work if a specific receptor is present on breast cancer cells. HR-positive/HER2-negative advanced or metastatic breast cancer can be treated with sacituzumab govitecan. This is a summary of the results of the TROPiCS-02 study. This study compared sacituzumab govitecan with standard chemotherapy in participants with HR-positive/HER2-negative advanced or metastatic breast cancer. WHAT WERE THE RESULTS?: The study showed that participants treated with sacituzumab govitecan lived significantly longer without their cancer getting worse than participants treated with chemotherapy. Participants also survived significantly longer and their tumors became significantly smaller in more participants treated with sacituzumab govitecan than with chemotherapy. In general, participants treated with sacituzumab govitecan were more likely to have side effects and had more severe side effects. These side effects included low levels of a type of white blood cell known as neutrophils and diarrhea. Oncologists (doctors that treat cancer) know of these side effects as they are common among people being treated for cancer. Doctors can control these side effects by following standard treatment guidelines and the package insert for sacituzumab govitecan. Participants treated with sacituzumab govitecan maintained their sense of well-being and ability to do daily activities (quality of life) longer than participants treated with chemotherapy. It also took longer for fatigue and other symptoms of cancer to worsen in participants treated with sacituzumab govitecan compared with chemotherapy. WHAT DO THE RESULTS MEAN?: Sacituzumab govitecan is more effective than standard chemotherapies for people who have already received multiple treatments for HR-positive/ HER2-negative advanced breast cancer. The side effects from sacituzumab govitecan could generally be managed well by doctors. Although there were more side effects with sacituzumab govitecan than with chemotherapy, they were generally mild to moderate.

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.