Dylann Cohn-Emery

Health-related quality of life (HRQOL), which measures the impact of health conditions on patients’ functioning, was maintained for longer in patients with HR-positive, HER2-negative breast cancer who were treated with Truqap (capivasertib) plus Faslodex (fulvestrant) compared to those who were treated with a placebo plus Faslodex, according to the patient-reported outcome (PRO) results of the CAPItello-291 trial.

, Dr. Mafalda Oliveira, discussed the PROs from the phase 3 CAPItello-291 study using data from three PRO questionnaires. These included the EORTC QLQ-C30, EORTC QLQ-BR23 and the Patient Global Impression of Treatment Tolerability.

In previously reported data, patients with aromatase inhibitor (AI)-resistant advanced breast cancer showed significant improvement with Truqap compared with placebo in terms of progression-free survival (PFS; time from treatment until disease worsening or death) in the overall population and in patients with 

Truqap-Faslodex Offers ‘More Options’ for Some With Breast Cancer Subset

Health-related quality of life (HRQOL),was maintained for longer in patients with HR-positive, HER2-negative breast cancer who were treated with Truqap plus Faslodex, according to study data.

“As new targeted drugs are approved for the treatment of breast cancer, assessment of HRQOL and patient experience is of growing importance and can actually supplement evaluation of the risk-benefit profile of treatment,” Oliveira, a medical oncologist in the Department of Medical Oncology at Vall d'Hebron University Hospital in Spain, said in her presentation.

The EORTC QLQ-C30 and EORTC QLQ-BR23 functional and symptom domains, except for diarrhea, were maintained in patients receiving with the Truqap combination longer than for those receiving placebo. There was more than a 10-point change in diarrhea symptom scores in the QLQ-C30 for Truqap, which was consistent with its known safety profile.

In CAPItello-291, 708 patients were randomly assigned to the Truqap/Faslodec arm (355 patients) or the placebo/Faslodex arm (353 patients). For all three PRO assessments, the baseline and overall compliance rates were similarly high between treatment arms, above 80% for each and though compliance was lower up to cycle 6, it was similar between arms.

The mean baseline scores for EORTC QLQ-C30 were similar between the two arms across subscales and both arms had consistent global health status (GHS)/QOL scores maintained from baseline. Truqap was not associated with clinically meaningful changes in the functional and symptom domain scores for EORTC QLQ-C30, except for a worse score for diarrhea.

In the EORTC QLQ-C30 and QLQ-BR23, time to deterioration (TTD; when quality of life decreases) for GHS/QOL was longer for patients in the Truqap/Faslodex arm. Except for diarrhea, the EORTC QLQ-C30 TTD for functional domains and symptom scales favored Truqap numerically, including in pain and fatigue. Diarrhea with Truqap/Faslodex was grade 1/2 in 63.1% of patients and the combination led to low rates of dose reductions, interruptions and discontinuations in 7.9%, 9.9% and 2.0% of patients, respectively. The TTD also numerically favored Truqap in the EORTC QLQ-BR23.

Both treatment arms reported that most patients were either “not at all” or “a little bit bothered by side effects from therapy in the Patient Global Impression of Treatment Tolerability assessment. In the first two cycles, the treatment differences were the highest, with more patients receiving Truqap reporting they were “somewhat,” “quite a bit,” or very much” bothered by side effects. However, these differences subsided after cycle 2.

The methods used for assessment of PROs using EORTC QLQ-C30 and EORTC QLQ-BR23 required patients to complete these questionnaires on day 1 of cycle 1 and every four weeks until second progression and at the progression or discontinuation visit. For the Patient Global Impression of Treatment Tolerability questionnaire, patients were to complete it on day 1 of cycle 1 and every two weeks after, then every four weeks after week 12 until discontinuation, and four weeks after discontinuation.

In the phase 3, double-blind, randomized CAPItello-291 trial, the overall population of patients with HR-positive, HER2-negative, AI-resistant advanced breast cancer given Truqap/Faslodex had a median PFS of 7.2 months compared with 3.6 with placebo/Faslodex. Patients with AKT pathway alterations (69.1%) had a median PFS of 7.3 months compared with 3.1 months for Truqap vs placebo, respectively.

“In conclusion, together with the clinical efficacy and manageable safety profile of (Truqap) plus (Faslodex), the results of this PRO analysis further support positive benefit-risk profile for the combination of (Truqap) and (Faslodex) in AI-resistant, HR-positive, HER2-negative advanced breast cancer,” Oliveira noted.

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Patients with HR-positive, HER2-negative breast cancer tended to have longer health-related quality of life and improved outcomes with Truqap plus Faslodex, research showed. 

Truqap Plus Faslodex Boosts Breast Cancer Outcomes, Quality of Life

Almost every patient with mismatch repair-deficient colon cancer enrolled onto a multicenter clinical trial achieved some type of response when treated with the neoadjuvant combination of Opdivo (nivolumab) and Yervoy (ipilimumab), according to recently presented findings.

The data — which were unveiled at the 2022 

European Society of Medical Oncology Congress

 — also demonstrated that 98% of the 112 patients enrolled onto the trial received surgery within six weeks of starting treatment.

According to the National Cancer Institute, neoadjuvant therapy is an initial treatment that is given to patients to shrink their tumor before they undergo surgery.

Here, the investigators launched the NICHE-2 trial after observing a group of 32 patients with nonmetastatic, mismatch repair-deficient colon cancer achieve a 100% pathologic response (the disappearance of some or all traces of cancer in tissue samples removed during surgery) rate when treated with an immune checkpoint inhibitor. The same findings showed that of the responses to the treatment, 60% of patients derived a complete response, meaning all signs of disease were gone.

In the NICHE-2 trial, 112 patients were administered Opdivo plus Yervoy during their first cycle of treatment. Then, the patients received only Opdivo two weeks later followed by surgery within six weeks of enrolling onto the trial. Assessing the three-year disease-free survival (time after treatment has ended that a patient remains alive without signs or symptoms of their cancer) rate and safety of the neoadjuvant combination of Opdivo and Yervoy were the main goals of the study.

The authors also aimed to investigate the major pathological response rate, as well as the complete pathological response rate. A major pathologic response was defined as 10% or less residual tumor remaining following the completion of neoadjuvant treatment.

The findings from the NICHE-2 trial showed that treatment with Opdivo plus Yervoy for four weeks was associated with a major pathologic response rate of 95%.

This outcome, according to one of the study authors, is a major improvement over what has been seen in the past for these patients.

“This stands in stark contrast to data from neoadjuvant chemotherapy in this same patient population (that had) only 7% pathologic responses,” Dr. Myriam Chalabi, a medical oncologist at the Netherlands Cancer Institute in Amsterdam, said in her presentation of the data.

Additionally, 67% of patients demonstrated pathologic complete responses and none have had a disease recurrence as of the last evaluation of the data. The presurgical treatment with Opdivo plus Yervoy was also well tolerated, with investigators observing only 4% serious or severe immune-related side effects.

Immunotherapy helps boost a person's immune system to help the body find and destroy cancer cells, according to the American Society of Clinical Oncology. Since immunotherapy activates the immune system, it can cause inflammation in any of the organs within the body, which can lead to complications called immune-related side effects.

The median time from the first treatment with the combination of Opdivo and Yervoy to surgery was 5.4 weeks. The investigators noted that there were no new safety signals but explained that 21% of patients had a surgery-related side effect of any severity. Thirteen percent of those side effects were serious or worse.

The investigators observed a major pathologic response in 102 patients, and a pathologic complete response in 72 patients following neoadjuvant treatment with Opdivo plus Yervoy.

Overall, 61% of the patient population experienced an immune-related side effect of any severity. However, only two patients had an immune-related side effect that lead to a more than two week delay in surgery. The most common mild to moderate side effects included infusion reactions, dry mouth, over- or underactive thyroid function, fatigue and flu-like symptoms.

The findings from the three-year disease-free survival analysis are expected to be available next year. Chalabi noted that future studies may observe organ-sparing approaches for patients with mismatch repair-deficient colon cancer. An organ-sparing treatment approach aims to avoid invasive surgery and preserve the function of the affected organ.

“I believe that neoadjuvant immunotherapy has a very strong potential to become standard of care for patients with (mismatch repair deficient) colon cancer,” Chalabi concluded. “The future has never been brighter for this patient population, and for that, I urge the pharmaceutical companies to please strive for registration of neoadjuvant immunotherapy.”

None of the more than 100 evaluable patients with mismatch repair deficient colon cancer have experienced disease recurrence after treatment with presurgical Opdivo plus Yervoy, according to study results.

Presurgical Opdivo-Yervoy Combo Has ‘Very Strong Potential’ to Be Standard of Care for Subgroup of Patients With Colon Cancer

The use of Calquence (acalabrutinib) was associated with fewer cardiovascular-related toxicities as well as a lower overall toxicity burden among patients with chronic lymphocytic leukemia (CLL), compared with Imbruvica (ibrutinib), according to recent findings.

The study authors conducted an analysis of data from the phase 3 ELEVATE-RR trial which had previously shown that treatment with the Bruton’s tyrosine kinase (BTK) inhibitor Calquence resulted in progression-free survival outcomes that were noninferior to those that occurred with Imbruvica — another BTK inhibitor — in patients with previously treated CLL.

This analysis, the results of which were presented at the recent 

2021 American Society of Hematology (ASH) Annual Meeting

, was conducted to further assess the occurrence of BTK inhibitor-associated side effects as well as the toxicity profiles of Calquence and Imbruvica.

Measuring progression-free survival (or the time during and after treatment when the patient lives without disease progression) was the main goal of the trial. Other goals included observing the incidence of atrial fibrillation (AFib)/flutter of any severity, as well as serious or severe infections and overall survival.

“Event-based analyses demonstrated a higher BTK inhibitor–related toxicity burden with ibrutinib in this head-to-head trial,” John F. Seymour, from the Peter MacCallum Centre and the Royal Melbourne Hospital in Melbourne, Australia, said in his presentation. “Exposure-adjusted assessments of AFib/flutter, hypertension, and bleeding events demonstrated a lower cardiovascular-related toxicity burden with acalabrutinib compared to ibrutinib. Cumulative incidences of hypertension and AFib/flutter were also lower with acalabrutinib in patients without a prior history of these events.”

After a median follow-up of 41 months, investigators assessed events of clinical interest in 268 patients receiving Calquence and 265 patients receiving Imbruvica. Of these events, the occurrence of AFib/flutter, hypertension and bleeding of any severity were statistically higher with Imbruvica. Exposure-adjusted incidence and exposure-adjusted time with these events were about 1.5 to 4.1 times higher with Imbruvica.

Other common BTK–related side effects noted for being significantly higher with Imbruvica in this analysis were any-severity diarrhea (46% vs 35%), joint pain (23% vs 16%), back pain (13% vs 8%), muscle spasms (13% vs 6%), and shortness of breath (12% vs 4%). Incidence of any-severity contusion and urinary tract infection (UTI) were also higher in those who received Imbruvica. Besides UTI, exposure-adjusted incidence and exposure-adjusted time with events were about 1.4 to 13.1 times higher with Imbruvica.

The only side effects with statistically higher incidence with Calquence were any-severity headache and cough, which occurred at rates of 35% and 29%, respectively, versus 20% and 21% with Imbruvica.

Investigators observed a longer median time to onset of any-severity AFib/flutter with Calquence versus Imbruvica, at 28.8 months and 16 months, respectively. Hypertension of any severity had a similar median time to onset for both therapies. Concomitant medication use for AFib/flutter or hypertension for all patients was less common in those administered Calquence.

The cumulative incidence of AFib/flutter and hypertension of any severity were consistently lower with Calquence up to 36 months, according to Seymour. Additionally, incidence of these two side effects was lower in patient subgroups regardless of the number of prior therapies, age, and having no prior history of AFib/flutter and hypertension. For patients with no prior history of AFib/flutter or hypertension, there was a lower cumulative incidence in patients receiving Calquence compared with Imbruvica.

There was, however, a similar time to onset for Calquence and Imbruvica in terms of inducing bleeding events of any severity. But incidence was lower for the Calquence group regardless of age and in patients with 1 to 3 prior lines of therapy. Few patients in either treatment group required dose modification due to bleeding events. Also, fewer patients given Calquence used concomitant medication for bleeding events than patients given Imbruvica. Moreover, the cumulative incidence of bleeding of any severity over 36 months was lower in those treated with Calquence.

At the data cutoff, 43% of patients on the ELEVATE-RR trial were still receiving treatment.

Treatment with Calquence resulted in fewer toxicities, including atrial fibrillation, flutter and hypertension, in patients with previously treated chronic lymphocytic leukemia, compared with Imbruvica treatment, according to findings from the analysis of a phase 3 trial.

Dylann Cohn-Emery

Truqap Plus Faslodex Boosts Breast Cancer Outcomes, Quality of Life

Presurgical Opdivo-Yervoy Combo Has ‘Very Strong Potential’ to Be Standard of Care for Subgroup of Patients With Colon Cancer

Calquence Linked to Fewer Heart-Related, Other Toxicities in Patients With CLL Than Imbruvica

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