Colleen Moretti 

Radiotherapy can be effectively administered with next-generation hormonal therapy in phase 3 trials of patients with high-risk localized or locally advanced prostate cancer (HRLPC), according to updated baseline patient characteristics of the fully enrolled phase 3 ATLAS trial (NCT02951052), presented at the 2022 American Society of Clinical Oncology Annual Meeting.

“ATLAS is an example of how RT can be included in phase 3 trials of HRLPC in combination with next-generation hormonal therapy,” the study authors wrote in a poster of the study.

The current treatment approach for patients with HRLPC comprises androgen deprivation therapy (ADT) combined with radiotherapy (RT). Although effective in some patients, ADT plus RT doesn’t significantly reduce the risk for metastases and death.

In the ATLAS trial, investigators are assessing if adding apalutamide (Erleada) to ADT (gonadotropin-releasing hormone agonist [GnRHa]) and external beam radiation therapy (EBRT) is feasible in patients with high-risk disease. 

A total of 1,503 patients (median age, 67 years) are currently enrolled onto the trial. A total of 89% and 11% of patients have an ECOG PS of 0 or 1, respectively. In regard to tumor classification, 66% are high-risk and 34% are very high-risk. Median PSA is 6.3 ng/mL and cT2 in 44%, CT2 in 50% and cN1 in 13%.

“Baseline characteristics demonstrate high- and very higher-risk features of prostate cancer and pelvic nodal involvements in patients undergoing primary RT in clinical practice,” the researchers wrote.

In 90% of patients included in the study, RT use was standard EBRT to prostate/pelvis over 6-8 weeks (cumulative 78-81 GY); in 10% of patients recent hypofractionation schedules were applied, and 5.6% had EBRT combine with brachytherapy.

“The RT schedules applied reflect recent evidence and guideline changes for the use of hypofractionation in this patient population,” the researchers wrote.

Patients were randomized to APA or placebo plus GnRHa for 30 (28-d) treatment cycles. All patients received GnRHa and primary RT as standard of care. And the placebo group also received bicalutamide in the neoadjuvant setting, concurrent with RT.

The authors noted that the RT schedules in ATLAS mimic recent evidence and guideline changes for the use of hypofractionation in this group of patients.

Sandler H, Freedland S, Shore N, et al. Patient (pt) population and radiation therapy (RT) type in the long-term phase 3 double-blind, placebo (PBO)-controlled ATLAS study of apalutamide (APA) added to androgen deprivation therapy (ADT) in high-risk localized or locally advanced prostate cancer (HRLPC). J Clin Oncol. 2022; 40(suppl_16):5084. doi: 10.1200/JCO.2022.40.16_suppl.5084

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According to the phase 3 ATLAS trial, radiotherapy can be administered with next-generation hormonal therapy in phase 3 trials of patients with high-risk localized or locally advanced prostate cancer. 

Radiotherapy Can Be Paired with Next-Gen Hormonal Therapy in Phase 3 HRLPC Trials

According to study findings, patients with 

 exon 20 insertion-positive metastatic non-small cell lung cancer (NSCLC) with brain metastasis at presentation may have demonstrated limited intercranial activity with mobocertinib (Exkivity) treatment , according to study findings presented at the 2022 American Society of Clinical Oncology Annual Meeting.

The data, which were presented at the 2022 American Society of Clinical Oncology Annual Meeting, indicated that patients who did not have brain metastases at enrollment onto the trial, but their disease progressed to the brain after initial mobocertinib treatment derived a benefit from remaining on study therapy.

“Patients with disease progression in the brain may derive overall benefit from ongoing mobocertinib treatment with combination [radiotherapy] to treat the brain lesions,” the authors wrote in their presentation.

This 3-part, open label, multicenter study (NCT02716116) comprised 114 patients [median age, 60 years; 66% female; 60% Asian) with an ECOG status 0 to 1 who had at least 1 or more prior lines of therapy for locally advanced/metastatic 

 exon 20 insertion-positive NSCLC. At baseline, 35% of patients had brain metastases.

Patients received mobocertinib at 160 mg once daily and were allowed to continue treatment beyond progressive disease at the discretion of the investigator if there was determined to be a clinical benefit. Additionally, patients with brain metastases were required to have the brain lesions treated and no symptoms of such prior to enrollment.

Confirmed objective response rate (cORR) was 28% (n = 32;) and median duration of response (DOR) was 17.5 months in the overall platinum-pretreated cohort (n = 64). Additionally, cORR was 34% (n = 25) among previously treated patients with no baseline brain metastases, compared with 18% (n = 7) among those with baseline metastases; and progression free survival was 9.2 and 3.7 months, respectively.

Among patients in the platinum-pretreated cohort, 21 (33%) had a first site of the disease involving the brain and 11 (17%) had first site of disease progression in the brain only. Of those 21 patients, 81% remained on mobocertinib beyond disease progression and 19% continued treatment for at least 6 months. And out of 43 patients who had first site of disease progression that did not involve the brain, 65% continued treatment with mobocertinib — 9% for at least 6 months.

“These results suggest that mobocertinib may have limited intercranial activity given the high frequency of first PD in brain (25%) and numerically IRC-assessed cORR in patients with baseline brain metastases,” the authors wrote in the abstract.

Of the 21 patients with first site of disease progression in the brain, 7 received brain radiotherapy and remained on mobocertinib (3 patients for 6 months or more and 1 patient for 12 months or more). Additionally, 12 patients remained on this treatment but did not receive radiotherapy.

“Optimal strategies for treating advanced 

 exon-driven NSCLC with brain metastasis warrant continued investigation,” the authors concluded in their abstract.

1. Jaane P, Ramalingam S, Yang J, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic non–small cell lung cancer (mNSCLC): treatment (tx) beyond progressive disease (PD) in platinum-pretreated patients (pts) with and without intracranial PD. 

. 2022; 40 (suppl_16):9099. doi: 10.1200/JCO.2022.40.16_suppl.9099

In patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer that has progressed after mobocertinib treatment, remaining on mobocertinib may be warranted, according to news research.

NSCLC With Baseline Brain Metastases Predictive of Limited Benefit from Mobocertinib

In patients with newly diagnosed mantle cell lymphoma (MCL), the addition of ibrutinib (Imbruvica) to the standard-of-care treatment of bendamustine (Bendeka) and rituximab (Rituxan) significantly improved progression-free survival (PFS) by 2.3 years, which was a 50% improvement compared with placebo and standard of care, according to results of the phase 3 SHINE trial (NCT01776840).

Findings presented at the 2022 ASCO Annual Meeting demonstrated that at a median follow-up of 84.7 months, treatment with the ibrutinib-based regimen (n = 261) induced a median PFS of 6.7 years (80.6 months), compared with a median of 4.4 years (52.9 months) in the placebo-based arm (HR, 0.75; one-sided 

Michael Wang, MD, lead study author and professor, department of lymphoma and myeloma, The University of Texas MD Anderson Cancer Center, noted that this is the first phase 3 clinical trial to demonstrate highly effective results with the combination of ibrutinib and chemoimmunotherapy.

“Indeed, this is very meaningful,” he explained during the presentation. “In this regimen we achieved 6.7 years without any disease. This is … a really remarkable achievement in the field of use for these patients.”

He noted it is also the highest PFS rate ever reported for this hard-to-treat population.

Some lymphoma treatments, such as intensive chemotherapy, targeted agents or transplantation are often unsuitable for the older MCL patient population. These treatments may be associated with the onset of severe adverse events (AEs) and older adults don’t typically respond well to them. However, this patient population is often underrepresented in clinical trials.

Wang noted that identifying an effective treatment for this patient population is an “urgent unmet need.”

Wang and colleagues compared ibrutinib (560 mg orally daily) in combination with bendamustine-rituximab (90 mg/m2; 375 mg/m2, respectively), to placebo plus bendamustine-rituximab in patients aged 65 years or older (median age, 71 years; range, 65-87).

Additional results demonstrated a complete response rate of 65.5% in the ibrutinib arm and 57.6% in the placebo arm (

 = .0567). However, there was no statistical significance in overall survival between the two treatment arms (

Time to next treatment was longer with ibrutinib than placebo (P <.001). And 52 (19.9%) patients on ibrutinib and 106 (40.5%) patients on placebo received subsequent anti-lymphoma therapies.

Grade 3 or 4 treatment-emergent AEs occurred in 81.5% and 77.3% of patients in the ibrutinib and placebo arms, respectively. Notably, atrial fibrillation was reported in 13.9% and 6.5% of patients in each arm, respectively. Other side effects noted by Wang included neutropenia, rash and pneumonia. Rates of major hemorrhage, hypertension, arthralgia and second primary malignancies were similar in both arms. Wang added that this safety profile was “no surprise” and was consistent with what has been reported in daily practice with ibrutinib.

“We believe this phase 3 clinical trial set a new benchmark for patients with a newly diagnosed (MCL) and the elderly and for those patients who are not eligible for autologous stem cell transplantation,” he concluded.

Wang M, Jurczak W, Jerkeman M et al. Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrutinib in combination with bendamustine-rituximab (BR) and R maintenance as a first-line treatment for older patients with mantle cell lymphoma (MCL). J Clin Oncol. 2022; 40(suppl_17):LBA7502. Doi: 10.1200/JCO.2022.40.17_suppl.LBA7502

Ibrutinib combined with bendamustine and rituximab extended the highest progression-free survival rate ever reported for this patient population, in the phase 3 SHINE study. 

Ibrutinib With SOC Shows Significant PFS Improvement in Older Patients With MCL

Although Black patients with metastatic breast cancer have the highest death rate and shortest survival outcomes when compared with other racial and ethnic groups in the United States, they are far less likely to be included in clinical trials that investigate newer treatments.

Findings from a recently completed survey demonstrated that although 83% of Black patients with metastatic breast cancer would be interested in participating in clinical trials, only 40% reported their provider having a conversation with them about a trial.

The results of the survey, which were presented during a press briefing ahead of the 2022 ASCO Annual Meeting, show that action needs to be taken to address these barriers and ensure more Black patients with metastatic breast cancer are included in clinical trials.

According to the presenter, only when a trial population represents the diversity of the general population can oncologists truly evaluate how a treatment works across different populations.

The purpose of the survey, which is a part of the BECOME initiative, was to better understand the barriers Black patients with metastatic breast cancer face in regard to participating in clinical trials. It was administered via social media, as well as by members of the Metastatic Breast Cancer Alliance and included 424 patients with metastatic breast cancer, 102 who self-identified as Black.

Black respondents trust and satisfaction rates with their oncology team were high, above 90%, and 83% of Black respondents were somewhat or very likely to consider participation in a clinical trial. However, 40% reported that their care team had not discussed clinical trials with them.

Additionally, Black respondents were more likely than non-Black respondents to believe unstudied treatments may be harmful (57% versus 31%) and were less likely to trust trials (73% versus 91%).

Other reasons for not participating in a clinical trial included worry about side effects (73%) and effectiveness (63%), as well as logistics such as travel and added cost.

Black respondents were also less likely than non-Black respondents to trust that people of all race and ethnicities would be given fair treatment in a trial (32% versus 56%) and would be more motivated to participate if there were assurance people of their race would benefit (83%).

Furthermore, Black respondents were more likely than non-Black respondents to value information on clinical trials if given by someone who is same race or ethnicity (67% versus 10%), has had breast cancer (73% versus 44%) or metastatic breast cancer (73% versus 51%).

Regarding forward steps, the presented said that all stakeholders have a role to play in increasing participation. This includes expanding the survey-respondent base, meaning investigators hope to reach a broader group of people to better represent the Black patient experience. Members of the BECOME initiative will also meet with other groups to share results and create strategies to improve care, she said.

Walker S, Carlson M, White C et al. Increasing Black patient participation in metastatic breast cancer clinical trials: The BECOME (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement) project. Presented at the 2022 ASCO Annual Meeting. May 26, 2022.

According to a survey, some Black patients with metastatic breast cancer harbor distrust toward clinical trials, which has impacted the number of Black patients who participate. 

Distrust Among Black Patients With mBC Impacts Participation in Clinical Trials 

In patients with advanced metastatic renal cell carcinoma (mRCC), treatment with cabozantinib (Cabometyx) directly after immunotherapy (IO) combinations was deemed safe and feasible, with no new safety signals, according to data presented at the 2022 ASCO Genitourinary Cancers Symposium.

Viktor Grüwald, MD, PhD, who presented the findings and professor of interdisciplinary genitourinary oncology at the University Hospital in Essen, Germany, explained that these data are similar to prior data, such as from the METEOR study (NCT01865747) from 2016, and confirm the use of cabozantinib in this setting.

“I think what we have seen is that it’s quite confirming that even … our real-world population was really coming close to the efficacy data that we have seen in the METEOR study, and that’s something that I think is quite compelling in terms of the role of cabozantinib after the failure of immuno agents. And because there is just scarce data, I think it is important to see that the recommendations that we gave in guidelines are quite supported. They’re supported by our data actually,” he said in an interview with Targeted Oncology™’s sister publication CURE®.

Grünwald explained that data on cabozantinib after IO combinations in mRCC still remains scarce, so he and researchers further evaluated the safety and efficacy of cabozantinib after IO-based therapy with a primary endpoint of the incidence of serious adverse events (SAE).

With a cutoff date of October 8, 2021, the final analysis included 56 eligible patients (71.4% male) with a median age of 66 years. There were 87.5% of patients (n = 49) who had a nephrectomy, 66.1% (n = 37) had clear cell RCC and 89.3% (n = 50) had 2 or more previous lines of therapy.

The usual dosing of cabozantinib is 60 mg, and 62.5% (n = 35) of patients started at a reduced dose at the start of treatment, 55.4% (n = 31) required a dose reduction during treatment and 1.8% (n = 1) discontinued treatment during this study. The median treatment duration was 6.1 months. During this time, 10.7% (n = 6) of patients had a partial response, 19.6% (n = 11) had stable disease and12.5% (n = 7) had progressive disease.

Overall survival (OS) and progression-free survival (PFS) were assessed from the start of therapy, and researchers compared these data with 20 patients who had a starting dose of 60 mg (cohort A) to those receiving less than 60 mg (cohort B) in a post-hoc analysis.

Results demonstrated the median OS and PFS of 15.34 months (95% CI; 8.94, 20.93) and 6.34 months (95% CI, 5.29-8.25) in the intention-to-treat population, respectively. In addition, median OS and PFS in cohort A were 10.48 months (95% CI, 6.01-34.14) and 6.51 months (95% CI, 2.99-10.87. In cohort B, median OS and PFS were 16.46 months (95% CI, 9.56-23.33) and 6.34 months (95% CI, 4.86-8.71).

“The data that we generated is clinically meaningful because it is a common practice and our data supports the current clinical practice,” Grünwald added. “… I think it reassures the role of cabozantinib. Something that it brings up is the role of the dose of cabozantinib, of course, and as it appears, even in the METEOR study, about half of the patients needed some dose reductions and the median dose was about 40 milligrams. So at the end of the day, I think 40 milligrams is a good starting point for cabozantinib.”

Additionally, those who started on the lower dose experienced fewer side effects compared to those who started on 60 mg. All grade AEs and grade 3-5 AEs occurred in 87.5% (n = 49) of patients and 44.6% (n = 25) in ITT. In cohort A, all-grade AEs and grade 3-5 AEs occurred in 95% (n = 19) of patients and 55% (n = 11), respectively.These also occurred in 85.7% (n = 30) and 40% (n = 14) of patients in cohort B.

In addition, SAEs were reported in 21.4% (n = 12) of patients from the entire study, including 30% (n = 6) from cohort A and 17.1% (n = 6) in cohort B. Treatment-related SAEs occurred in 10.7% (n = 6) of patients in this study, including 15% (n = 3) of those in cohort A and 8.6% (n = 3) in cohort B.

“Overall, it’s well tolerated and well manageable. … We don’t have any additional safety signals here. And it is similar to what we have seen in other studies actually in terms of safety profiles. So nothing unexpected,” he explained.

Gründwald said the main point here is that the data supports the use of cabozantinib after IO failure as it is safe a feasible, and the only thing that will need further research is dose reduction.

“Our data really supports the use of cabozantinib after IO failure. I think that's the main message. It's safe, tolerable and it’s efficacious,” he concluded. “It supports the use of 40 (mg) as well as 60 (mg), and that I think is a novelty because 60 mg is the licensed dose for the use of cabozantinib vs. single agent.”

Grünwald, V, Boegemann M, Rafiyan M-R, et al. Final analysis of a non-interventional study on cabozantinib in patients with advanced renal cell carcinoma after prior checkpoint inhibitor therapy (CaboCHECK). Presented at the 2022 ASCO Genitourinary Cancers Symposium; February 17-19, 2022; Abstract #357

New data presented during the Genitourinary Cancers Symposium support the using cabozantinib after immunotherapy without new safety signals.

Cabozantinib Following IO Therapy Failure Confirmed Safe, Feasible in Metastatic RCC

Compared with the combination of fludarabine, cyclophosphamide, and rituximab (FCR), patients with previously untreated chronic lymphocytic leukemia (CLL) achieved superior progression-free survival (PFS) rates following treatment with ibrutinib (Imbruvica) plus rituximab (Rituxan), according to trial results presented at the 2021 ASH Annual Meeting and Exposition. 

At a median follow up of 52.7 months, a median PFS was not yet reached in the ibrutinib and rituximab arm vs 66.53 months in the FCR arm (HR, 0.44; 95% CI; 0.32-0.60; 

PFS was also significantly better with ibrutinib and rituximab in patients with IGHV unmutated CLL (HR, 0.4; 

 = .001), and normal karyotype (HR, 0.37; 

 = .001) but not for patients with IGHV mutated CLL at follow up (HR, 0.68; 

The FLAIR trial (ISRCTN0844152) is an ongoing, phase III, multicenter, randomized, controlled, open, parallel group trial and includes a total of 771 patients (73.3% are male, median age, 62 years) from 113 United Kingdom-based centers who were enrolled onto trial between Sept. 19, 2014, and July 19, 2018. The data was locked on May 24, 2021. Patients who were aged over 75 years and had >20% 17p-deleted cells were excluded. Secondary endpoints included overall survival (OS), attainment of undetectable MRD, response to therapy, safety and toxicity, health-related quality of life (HRQoL), and cost-effectiveness.

Patients were randomized on a 1:1 basis to receive either 6 cycles of FCR (oral fludarabine at 24 mg/m2 / day for 5 days, oral cyclophosphamide 150 mg/ m2/ day for 5 days with IV rituximab [375 mg/m2 on day 1/ 2 of cycle 1; 500 mg/m2 on day 1 of cycles 2-6]; n= 385) every 28 days or ibrutinib at 420 mg/day plus rituximab (6 doses as of FCR) given for up to 6 years with stratification by disease stages, age, gender, and center.

A total of 59 and 21 patients received second-line treatment after FCR and ibrutinib plus rituximab, respectively, and 88.1% of patients received targeted therapies for CLL progression after FCR. 

At a median follow-up of 50.2 months, OS was not different between the 2 arms (HR, 1.01; 

 = .956) with 29 deaths in the FCR arm (4 from CLL, 3 from Richter’s [RT], 3 AML/MDS, 3 COVID-19 and 2 cardiac/sudden) and 30 in the ibrutinib arm (3 from CLL, 1 from RT, 3 COVID-19 and 8 cardiac/sudden). 

“There is no difference in overall survival, but almost all patients relapsing after FCR received either ibrutinib or venetoclax plus rituximab,” the researchers wrote in the presentation.

Notably, 4-year OS significantly improved with FCR in the FLAIR trial at 94.5%, compared with 84.2% in other trials between 2009 and 2012.

The researchers highlighted results from the ADMIRE and ARCTIC trials, both of which had the same inclusion criteria, centers, and an identical FCR schedule, however those were conducted prior to the availability of targeted therapies in the relapse setting.

At 3 months post treatment, 60.5% of patients (n = 233) in the FCR arm and 21.0% (n = 81) in the ibrutinib plus rituximab arm achieved a IWCLL complete response, 27.6% (n = 106) and 70.2% (n = 271) achieved a partial response, respectively, and 11.9% (n = 46) and 8.8% (n = 34) had either stable disease, progressive disease or no response.

Overall, a greater percentage of patients in the FCR arm (55.3%) became MRD negative via the bone morrow at 3 months post-treatment compared with the ibrutinib and rituximab arm (3.9%).

Serious adverse events (SAEs) occurred in 53.7% and 53.4% of patients in FCR and ibrutinib arms, respectively. Differences in SAEs by organ class for FCR vs ibrutinib plus rituximab were 33.6% vs 27.1%; blood and lymphatic in 19.8% vs 10.7%; and cardiac in 1.1% vs 8.3%, respectively.

Ten deaths, 8 of which occurred in the ibrutinib and rituximab arm, were attributed to sudden or cardiac events. Further analysis, according to the authors, identified that 7 of the deaths that occurred in the ibrutinib and rituximab arm were in patients who had a history of hypertension or cardiac disease, whereas the patients who accounted for the two deaths in the FCR arm did not have a history of either condition.

Additionally, there were 6 cases of secondary MDS/AML in the FCR arm and 1 in the ibrutinib and rituximab arm.

Hillmen, P, Pitchford, A, Bloor, A, et al. Ibrutinib Plus Rituximab Is Superior to FCR in Previously Untreated CLL: Results of the Phase III NCRI FLAIR Trial. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Virtual. Abstract: 642.

While no significant difference in overall survival benefit between the treatment groups was observed, almost all patients switched from FCR to ibrutinib or another regimen after disease relapse. 