Matthew Fowler

Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) achieved adequate responses to the first-line treatment of Imbruvica (ibrutinib) plus Venclexta (venetoclax), according to recent findings.

Data from the phase 2 CAPTIVATE study, which were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated that treatment with the combination was similarly associated with high rates of overall survival (time from diagnosis or treatment start when patients are alive) and progression-free survival (time during and after treatment when the patient lives without disease progression).

The data presented at the ASCO Annual Meeting focused on the fixed-duration treatment group of the CAPTIVATE study, with patients receiving three cycles of Imbruvica followed by 12 cycles of Imbruvica plus Venclexta. A total of 159 previously untreated patients with CLL and SLL aged 70 years or younger with an ECOG performance score (a patients level of functioning and ability to care for themselves with 0 being fully active and 4 being disabled) of 0 to 2 were enrolled onto the trial.

Ninety-two percent of the patients completed the 12 cycles of Imbruvica plus Venclexta. The median time on study was 27.9 months with a median treatment duration of 13.8 months. The median follow-up was 14.0 months after treatment completion

In patients whose disease did not harbor a deletion 17p mutation, the combination induced a complete response rate of 56% and 55% in the all-treated patient population. The only exception was observed in the bulky disease category, where patients with bulky disease had a complete response rate of 31%.

Further, for patients with bone marrow or peripheral disease, high rates of undetectable minimal residual disease (a small number of cancer cells that could be detected during or after treatment) were observed, including in patients with high-risk disease features.

When examining patients at 24 months, those without the deletion 17p mutation treated with the combination had a 96% progression-free survival rate. For overall survival, the 24-month rate was 98% in the same patient population. The median follow-up time was 27.9 months.

The most common side effects of any severity in the combination treatment group were diarrhea (62%), nausea (43%), neutropenia (low count of neutrophils or white blood cells; 42%), and joint pain (33%). Serious or severe side effects included neutropenia (33%), infections (8%), hypertension (6%), and neutrophil count decrease (5%). Twenty-three percent of patients experienced any serious side effect, with only one f death occurring.

“All of these results together support the idea of the combination of (Imbruvica) plus (Venclexta) as an all-oral, once daily, chemo(therapy)-free, fixed-duration (treatment) that may achieve deep responses and undetectable (minimal residual disease) in a vast majority of patients,” lead study author Dr. Paolo Ghia, of the Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele in Milan, Italy explained during a presentation of the findings.

This combination therapy is currently being examined in a complementary older population in a phase 3 trial, the results of which are expected soon.

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Treatment with this combination was associated with encouraging clinical responses in this patient population.

Front-Line Imbruvica-Venclexta Combo May Induce Durable Responses in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

with metastatic prostate cancer experienced prolonged survival as a result of treatment with the immunotherapy Yervoy (ipilimumab), according to study findings published in 

Researchers in the phase 2 trial found that certain patients with metastatic castration-resistant prostate cancer, which typically has a limited response to immunotherapy, could benefit from treatment with Yervoy. The investigation also uncovered biomarkers in the tumors that could help doctors identify patients most likely to respond to the medication. The participants who fared best were those whose tumors, before treatment, had a higher density of active T cells, also known as immune cells.

Yervoy is among a class of drugs known as checkpoint inhibitors, which interfere with the activity of proteins that otherwise keep the immune system in check. Yervoy targets the protein CTLA-4. These kinds of drugs free up the immune system to better recognize and kill cancer cells and tend to work best in tumors that have numerous mutations, such as melanoma and lung cancer. Prostate tumors have fairly low mutation levels, the authors pointed out, but immunotherapy also can be more effective in some tumors that express the protein PD-L1 or contain T cells.

The researchers, all from The University of Texas MD Anderson Cancer Center in Houston, knew that previous clinical trials had found some responses to immuno- therapy among patients with prostate cancer, so they focused on whether checkpoint inhibition could stimulate effective immune responses in tumors with low mutation levels. Their trial included 30 patients with metastatic castration-resistant prostate cancer; 29 were treated with Yervoy between January 2015 and May 2018, and one did not receive treatment.

After a median follow-up of 45.5 months, the researchers separated the patients into two groups based on length of life and time until disease grew or spread while receiving Yervoy. In the group that showed favorable results, six of nine patients were alive at the time of analysis, with survival ranging from 33 to 54 months. All 10 patients in the group with unfavorable results died of their disease, with survival ranging from 0.6 to 10.3 months from the start of treatment.

Across all participants, the median time until disease progression was three months and median overall survival was 24.3 months.

The researchers found a couple of reasons for the better outcomes. The men in the favorable group had a high level of cancer-killing CD8 T cells in their tumors and greater expression of the protein interferon gamma, another key to immunity. Furthermore, their T cells recognized and responded to the antigens produced by tumor cells, whereas T cells from patients in the unfavorable group did not appear to have those capabilities.

Eight patients (28%) experienced serious side effects from receiving Yervoy, with dermatitis and diarrhea among the most common.

“We were encouraged to see that prostate cancers with a low mutational burden do in fact express neoantigens that elicit T-cell responses that lead to favorable clinical outcomes,” co-lead corresponding author Dr. Padmanee Sharma said in a press release. “Our findings indicate

that anti-CTLA-4 immune checkpoint therapy warrants additional studies in order to develop treatment strategies that may improve survival of patients with metastatic prostate cancer.”

One immunotherapy is already approved for patients with prostate cancer, but it works differently from Yervoy. Provenge (sipuleucel-T) is made from a patient’s own harvested immune cells, which are exposed in a lab to a cancer-fighting protein and then infused back into the patient. Provenge is indicated to treat minimally symptomatic lower-burden metastatic prostate cancer and is not widely used.

Immunotherapy could help a segment of patients with metastatic prostate cancer, a study found.
 

Looking at Immunotherapies for Patients with Metastatic Prostate Cancer

Treatment with Tagrisso (osimertinib) following surgery is the first targeted agent in a global randomized trial to demonstrate statistically significant improvement of disease-free survival (DFS) in patients with stage 2-3A EGFR mutation-positive non-small cell lung cancer (NSCLC), according to results from the ADAURA trial presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

The risk of disease recurrence or death was reduced by 83% for patients with stage 2-3A disease treated with Tagrisso compared to placebo. There was also a consistent improvement of DFS, the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms, regardless of whether patients received adjuvant chemotherapy prior to enrollment.

“While osimertinib is already a standard of care for front-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer, the improvement in disease-free survival following surgery that was seen in the ADAURA study supports the use of this targeted therapy in an earlier stage of disease,” said ASCO chief medical officer and executive vice president Dr. Richard L. Schilsky.

The data showed DFS at two years was 90% for patients receiving study drug compared to 44% for those receiving placebo among patients with stage 2-3A NSCLC with an EGFR mutation. In the overall population (stage 1B-3A), DFS at two years was 89% for the Tagrisso group compared to 53% for the placebo group.

Even more, the overall population saw a 79% reduction in the risk of disease recurrence when treated with Tagrisso compared to placebo.

The trial consisted of 682 patients with primary non-squamous stage 1B-3A NSCLC and confirmed EGFR

mutation. The patient population was randomized to receive either adjuvant Tagrisso (n = 339) or placebo (n = 343) for up to three years. The study drug was administered to patients once daily via an 80 mg tablet.

In total, 31% in each group had stage 1B disease and 69% had stage 2/3A disease. A larger portion of both groups were female, with 68% in the study drug group and 72% in the placebo group.

The researchers chose a third-generation drug and placebo over first- or second-generation options — which showed no statistically significant impact on DFS in previous studies – to maximize positive effects through a longer time period so that the drug can safely be taken by patients.

“The feeling was that [first- and second-generation] drugs couldn’t be given for three years,” said lead study author Dr. Roy S. Herbst. “The ideal is to give the drug longer to hopefully have a much more profound effect on outcome. I think what we’ve shown in this trial is that we can give the [third generation] drug for longer periods of time.”

DFS in stage2/3A patients was the primary outcome in the study. Other secondary endpoints included DFS in the overall population; DFS at two, three, four, and five years; overall survival; safety; and quality of life.

Lung cancer accounts for more than 1.7 million deaths annually, making it the leading cause of cancer death globally. More specifically, NSCLC constitutes 85% of all lung cancer cases, with 30% of patients presenting with resectable disease at diagnosis.

Herbst, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital, explained that future studies are in the works regarding the DNA of patients drawn at regular intervals during the ADAURA trial to combat patients developing a resistance to these agents. More, neoadjuvant therapy is being examined to eventually “move the best drugs, the most targeted drugs, as early as possible in the disease.”

These results, according to the researchers, demonstrate that adjuvant Tagrisso provides a highly effective treatment for patients after complete tumor resection and is a viable alternative front-line therapy for localized NSCLC with EGFR mutation.

“The improvement in disease-free survival following surgery that was seen in the ADAURA study supports the use of this targeted therapy in an earlier stage of disease,” said ASCO chief medical officer and executive vice president Dr. Richard L. Schilsky.

Matthew Fowler

Front-Line Imbruvica-Venclexta Combo May Induce Durable Responses in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Looking at Immunotherapies for Patients with Metastatic Prostate Cancer

Tagrisso Following Surgery Improves Survival in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer

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