Brielle Benyon

Weekly dose-dense chemotherapy is not superior to standard 3 weekly chemotherapy for patients with epithelial ovarian cancer when it comes to progression-free survival (PFS) and overall survival (OS), though the regimen is safe and effective, according to results from the ICON8 study presented at the ESMO Virtual Congress 2020.

“[For] the most of the last 3 decades, platinum paclitaxel doublet chemotherapy administered on a once every 3 week schedule for 6 to 8 cycles has been cornerstone in the first-line modality management of epithelial ovarian cancer,” said chief investigator Andrew Clamp, BMBCh, senior lecturer and honorary consultant in medical oncology at the Christie NHS Foundation Trust.

ICON8 included 1566 patients with epithelial ovarian cancer who had FIGO stage IcG3-IV disease. Participants were randomized 1:1:1 to 3 arms:

Arm 1, standard chemotherapy, q3w carboplatin AUC5/6 plus q3w paclitaxel 175 mg/m

Arm 2, weekly paclitaxel (q3w carboplatin AUC5/6 plus q1w paclitaxel 80mg/m

Arm 3, weekly carboplatin-paclitaxel (q1w carboplatin AUC2 plus q1w paclitaxel 80 mg/m

“There’s a strong rationale for the evaluation of weekly dose paclitaxel after settling in to the first line of treatment,” Clamp said, citing preclinical animal evidence of metronomic taxane treatment could improve drug delivery, increase tumor cell apoptosis, and reduce angiogenesis.

Baseline characteristics were well balanced among the arms. The median age of study participant was 62; 72% had serous histology; 10.5% were stage Ic-IIa; 18% were stage IIa-IIIb; and 71% were stage IIIc-IV. Half (50%) of patients planned delated primary surgery (DPS), while slightly less (48%) had immediate primary surgery (IPS). Two percent of patients were inoperable.

As of October 1, 2019, median OS was 47.4, 54.1, and 53.4 months in arms 1, 2, and 3, respectively. There were 319 deaths in arm 1 (61%), 300 deaths in arm 2 (57%), and 304 deaths in arm 3 (58%). There was no significant improvement in OS comparing arm 2 versus arm 1 (97.5% CI, 0.74-1.06; p=.14, HR =.88); arm 3 versus arm 1 (97.5% CI, 0.76-1.09; p=0.27, HR=0.91).

Median time to progression was 25, 25.5, and 25.9 months in arms 1, 2, and 3, respectively, again showing no statistically significant difference (arm 2 versus arm 1 p=0.37; arm 3 versus arm 1 p=0.48).

The toxicity profile of the weekly regimen was previously presented at the ESMO annual meeting in 2017, and Clamp said that there were no changes in adverse events.

“The two weekly treatment arms were associated with an increased incidence of any grade 3 or 4 events during treatment, but this was predominantly driven by uncomplicated growth [grade] 3 or 4 neutropenia,” Clamp said. “Reassuringly, incidence of febrile neutropenia was low in all 3 treatment arms, and we did not see any increase of grade 2 or more sensory neuropathy in the 2 weekly dose-dense paclitaxel-containing regimen.”

Ultimately, Clamp explained that since the dose-dense regimen did not show improved survival results, weekly paclitaxel can remain standard of care for this patient population, though more research is needed.

“Other further hypothesis-generating analyses are underway in our DPS cohort to determine if there is a subgroup of patients who may benefit with the more dense approach,” Clamp said.

Clamp AR, James EC, McNeish I, et. al. ICON8: overall survival results in a GCIC phase III randomized controlled trial of weekly dose-dense chemotherapy in first line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment. Presented at: ESMO Virtual Congress 2020, Sept. 19-21, 2020. Accessed Sept. 21, 2020.

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Weekly dose-dense chemotherapy is not superior to standard 3 weekly chemotherapy for patients with epithelial ovarian cancer when it comes to progression-free survival and overall survival, though the regimen is safe and effective.

Weekly Dose-Dense Chemotherapy Not Superior to Standard of Care in Epithelial Ovarian Cancer

Genetic testing is more important now than ever before, as biomarker-driven cancer treatments continue to receive approval across many tumor types. While these personalized treatments are improving outcomes, navigating the landscape of genetic testing can leave patients with questions for their providers.

 virtual meeting hosted by Physicians’ Education Resource®, LLC (

), Emily Mazzei, MS, MPH, CGC, a licensed, certified genetic counselor, provided an overview of current recommendations for genetic counseling in oncology and discussed some of the questions commonly asked.

Mazzei reviewed the difference between somatic testing, also known as germline or tumor testing, and germline testing. Somatic changes are not hereditary, as they occur in the cancer cells themselves, according to Mazzei; germline mutations are present in a patient since birth, since they are passed down from parents to children.

“Depending on what your patient population looks like, you may be seeing that your patients have 1 of these types of genetic tests or both,” Mazzei said. “Somatic testing is becoming a little more commonplace, or [even as] routine as genetic testing. Generally speaking, panel testing is now standard of care.”

In a panel test, patients will be tested for genes associated with their cancer, as well as those that typically fall outside of their cancer type. However, patient choice also plays a role in what kind of testing they will receive, noted Mazzei.

“It also depends on the patient’s preferences. Some want to just focus on the specific cancer type that they have,” Mazzei said. “It also depends on the institution and what the genetic counselors and ordering physicians prefer.”

Genetic Findings Affect Treatment and Family Members

Genetic testing results have become crucial in determining the type of treatment a patient receives. For example, the FDA most recently approved the combination of 

atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf)

 V600 mutation–positive melanoma. Only when a mutation or alteration has been detected can a patient be considered for a potential targeted treatment.

Additionally, if a germline mutation is detected in a patient, their immediate family may also be at higher risk for cancer, according to Mazzei. Family members are then faced with the decision of whether they want to undergo testing—that is not an easy choice for many people, Mazzei explained.

“A large part of our role is providing psychosocial support to these patients,” she said. “Essentially, we give them the information they need to help them make the decisions on whether they want to pursue genetic testing when it’s medically indicated.”

The cost of genetic testing is another concern that patients and their family members often have, particularly with regard to whether it will be covered by insurance, Mazzei noted.

“Most insurance companies will cover their genetic counseling, a face-to-face appointment with a genetic counselor,” Mazzei said. “Most insurance companies will cover all, or some, of the genetic or germline testing, if ordered appropriately and clinically indicated.”

As such, Mazzei recommended that prescribing clinicians work closely with genetic counselors to ensure that testing is correctly ordered, thus increasing the chance that it will be covered by their patients’ insurance.

While the majority of patients who undergo genetic testing for cancer are adults, there are some instances when children under the age of 18 should be tested, according to Mazzei.

Children who should be tested include those with a family history of a pathogenic gene mutation, such as polyposis syndromes, multiple endocrine neoplasia type 2, and Li Fraumeni syndrome (LFS). Those with a personal history or current diagnosis of cancer may also be tested. LFS can lead to potential increased risk of sarcoma, leukemia, and brain tumors, and PTEN Hamartoma Tumor Syndrome can lead to increased risk of macrocephaly, developmental delay, or thyroid cancer.

“The reason for [this testing in this population] is for medical intervention for these specific conditions,” Mazzei said.

However, not everyone under the age of 18 should be tested, despite their relatives’ genetic testing results or cancer history. For example, there is no medical intervention for children with 

“We also want the patient or the person pursuing genetic testing to be autonomous when making this decision, so that’s why we only recommend testing these childhood conditions and not adult-onset conditions, even though the parents may be wondering whether their child does have that,” Mazzei concluded.

Mazzei E. Cancer genetic counseling. Presented at: 4th Annual School of Nursing Oncology. July 31-August 1, 2020.

Genetic testing is more important now than ever before, as biomarker-driven cancer treatments continue to receive approval across many tumor types. 

Genetic Counselor Addresses Common Questions About Testing in Oncology

Teclistamab (JNJ-64007957) appeared to be a safe and efficacious treatment for patients with relapsed/refractory multiple myeloma, according to a phase I study presented at the ASCO Virtual Scientific Program. 

Another treatment option would be a welcome change for these patients, who tend to have poor prognoses once they run out of treatment options, according to Saad Z. Usmani, MD. After becoming refractory to available therapies, median overall survival (OS) is 6-11 months. 

“Multiple myeloma is a complex disease, and despite recent advances with new therapies, patient outcomes are poor once available classes of therapies are exhausted,” Usmani, chief of the Plasma Cell Disorders Program and director of Clinical Research in Hematologic Malignancies at the Levine Cancer Institute, Atrium Health, said while presenting the findings. 

The study (NCT03145181) involved 78 patients with relapsed/refractory myeloma who received teclistamab — a bispecific duo antibody that binds to BCMA and CD3 – intravenously. Median age was 64 years old (range, 24-82), and the median number of prior therapies was 6 (range, 2-14). Overall, 72% of participants were triple-class exposed, 62% triple-class refractory, and 51% penta-drug refractory. 

Part 1 of the study was a dose-escalation trial, with a primary objective of finding the doses for part 2. Doses ranged from 0.3-720 µg/kg weekly, and there was a 67% overall response rate (ORR; 50% ≥ VGPR) at 270 µg/kg. 

“Response rates increased with higher doses of teclistamab,” Usmani said. 

The drug became active in patients receiving 38.4 µg/kg or higher, with 21 out of 52 patients (38%) achieving a response, per IMWG criteria. Two patients were minimal residual disease (MRD)-evaluable per next-generation sequencing, and they both were MRD negative at 10

“Looking at the durability of response, we concluded that the responses deepened over time,” Usmani said, noting that 16 of the 21 patients who responded have an ongoing response. 

The most common adverse events (AEs) of all grades were cytokine release syndrome (CRS; 56%), neutropenia (26%), and anemia (23%). CRS typically occurred during the initial doses, and all CRS events were grade 1-2. Additionally, 8% of patients experienced a treatment-related neurotoxicity (grade 3 or higher, 3%) and 9% had an infusion-related reaction. 

A total of 61% of patients experienced an infection-related AE with 21% of them being grade 3 or higher. Reported dose-limiting toxicities were delirium (which was resolved after 16 days) and thrombocytopenia (resolved after 1 day). 

More than a third of patients (36%) had ≥3 AE, with neutropenia and anemia being the most frequent, occurring in 20% and 14% of patients, respectively. One grade 5 AE was reported and was respiratory failure in the setting of pneumonia that the investigator deemed unrelated. 

“Intermittent dosing is viable based on these data … teclistamab was manageable across all doses,” Usmani said.

Efficacy data at the 720 µg/kg dose are not yet mature, and the dose escalation and expansion phases of the trial are still ongoing, Usmani explained. Future findings could lay the groundwork for a promising new therapy for this patient population. 

“BCMA and CD3 bispecific antibody approaches offer an off-the-shelf, immune-mediated therapy for these patients,” Usmani said. 

Usmani SZ, Mateos M, Nahi H, et. al. Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (R/R MM). Presented at: 2020 ASCO Virtual Scientific Program. May 29-31, 2020. Abstract 100.

Teclistamab (JNJ-64007957) appeared to be a safe and efficacious treatment for patients with relapsed/refractory multiple myeloma.

Teclistamab Appears Safe at All Doses for Relapsed/Refractory Myeloma Treatment 

Zanubrutinib (Brukinsa) was associated with a higher complete response or very good partial response (CR+VGPR) rate, as well as clinically meaningful advantages in safety and tolerability, compared with ibrutinib (Imbruvica) in patients with Waldenström macroglobulinemia (WM), according to results of the phase 3 ASPEN trial (NCT03053440). However, the trial did not meet its primary study hypothesis, which was superiority with CR+VGPR by an independent review committee (IRC), in the zanubrutinib arm.

While not statistically significant, the data could spark change for patients with this rare type of blood cancer, according to Constantine Si Lun Tam, MD, MBBS, associate professor, department of Hematology, Peter MacCallum Cancer Centre, St. Vincent's Hospital, The University of Melbourne in Victoria, Australia. Tam recently discussed the trial at the 2020 ASCO Virtual Scientific Program.

"The totality of data from the two trials presented at ASCO suggests that zanubrutinib may be a preferred treatment option for patients with WM, regardless of whether they have received prior treatment," said Tam, principal investigator for the ASPEN trial, in a press release about the findings.

 mutation (N = 201) were randomized 1:1 to receive either 160 mg twice daily of zanubrutinib (n = 102) or 420 mg once daily of ibrutinib (n = 99). Patients were stratified based on CXC4 mutational status, as well as how many prior therapies they received (0; 1 to 3; and 3 or more). Another cohort of 28 patients without MYD88 mutations was also given 160 mg daily.

Notably, a third (33.3%) of the patients randomized to zanubrutinib were elderly (over 75 years), compared to 22.2% in the ibrutinib arm. Additionally, the zanubrutinib arm had higher rates of anemia than the ibrutinib group (hemoglobin ≤ 110 g/L; 65.7% versus 53.5%, respectively).

At median follow-up of 19.4 months, the rates of CR+VGPR for patients with 

 mutations — the primary endpoints – were 28.4% for the zanubrutinib arm and 19.2% for the ibrutinib arm (P=0.0921).

"WM can be a devastating disease for patients and their families. We must offer therapies that are both effective in managing WM and well-tolerated to offer the best quality of life. In the ASPEN trial, zanubrutinib demonstrated a more favorable safety profile and was shown to be a more tolerable option for patients than ibrutinib, especially when considering adverse events of particular interest such as atrial fibrillation, hypertension and diarrhea," Tam said.

The zanubrutinib arm also had lower rates of atrial fibrillation (2.0% versus 15.3%, respectively), hypertension (10.9% versus 17.3%), major bleeding (5.9% versus 9.2%), grade 3 or higher adverse events (AEs; 58.4% versus 63.3%), AEs leading to discontinuation (4.0% versus 9.2%), and AE-related deaths (1.0% versus 4.1%) compared to ibrutinib.

While the rate of grade 3 or higher infections was similar between the zanubrutinib and ibrutinib arm (17.8% versus 19.4%, respectively), zanubrutinib did have a higher rate of neutropenia (29.7% versus 13.3%).

"These results reinforce that zanubrutinib is a highly effective BTK inhibitor with clinically meaningful improvements in safety and tolerability compared to ibrutinib. Importantly, since WM is typically a disease of older individuals, zanubrutinib appears to have advantages related to cardiovascular safety risks over ibrutinib," said Jane Huang, MD, Chief Medical Officer, Hematology at BeiGene. "The choice to evaluate zanubrutinib directly against ibrutinib underscores our bold approach to R&D and our commitment to develop better treatments for patients across the globe."

Tam C, Opat S, D’Sa S, et. al. ASPEN: Results of a phase III randomized trial of zanubrutinib versus ibrutinib for patients with Waldenström macroglobulinemia (WM). Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract number 8007.

BeiGene Presents Updated Head to Head Results from Phase 3 Trial of Zanubrutinib vs. Ibrutinib in Patients with Waldenstrom’s Macroglobulinemia at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. Published May 29, 2020. https://www.globenewswire.com/news-release/2020/05/29/2040883/0/en/BeiGene-Presents-Updated-Head-to-Head-Results-from-Phase-3-Trial-of-Zanubrutinib-vs-Ibrutinib-in-Patients-with-Waldenstr%C3%B6m-s-Macroglobulinemia-at-the-2020-American-Society-of-Clini.html. Accessed May 29, 2020.

Zanubrutinib demonstrated a higher complete response or very good partial response rate compared with ibrutinib in patients with Waldenström macroglobulinemia, although the findings were not found to be statistically significant.

Author | Brielle Benyon

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