Chemotalk Newsletter

Chemotalk Newsletter, Vol. 116 December 1, 2017

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2018 HAS to be better...doesn't it?



By Dave Levitan

The addition of bevacizumab to adjuvant CHEMOTHERAPY failed to improve survival outcomes in patients with surgically resected early-stage NON-SMALL-CELL LUNG CANCER (NSCLC), according to a new randomized trial. The agent "does not have a role" in this setting, the investigators concluded.

"In the setting of advanced-stage NSCLC, the first agent to improve survival when added to a platinum doublet was bevacizumab," wrote authors led by Heather A. Wakelee, MD, of the Stanford Cancer Institute at Stanford University in California. The researchers tested whether the VEGF-targeted agent would be similarly effective in the early-stage NSCLC adjuvant setting, where patients remain at high risk of relapse despite chemotherapy.

The trial was an open-label, randomized, phase III study including 1,501 patients with completely resected stage IB to IIIA NSCLC. They were randomized to receive either chemotherapy alone (749 patients) or chemotherapy plus bevacizumab (752 patients); results were published in Lancet Oncology.

Patients had a median age of 61 years, and were evenly divided between men and women. Most patients were white (86% in the chemotherapy-alone group, 88% in the bevacizumab group), and four different chemotherapy regimens were used in largely even proportions (cisplatin along with either vinorelbine, docetaxel, gemcitabine, or pemetrexed).

The trial was stopped after a sixth planned interim analysis. At that point, the median follow-up for patients still alive was 50.3 months. The median overall survival with chemotherapy alone was not yet reached, and with bevacizumab it was 85.8 months; this yielded a hazard ratio (HR) for survival of 0.99 (95% CI, 0.82­1.19; P = .90).

The median disease-free survival was also similar, at 42.9 months without bevacizumab and 40.6 months with it, for an HR of 0.99 (95% CI, 0.86­1.15; P = .95). Subgroup analyses did not reveal many significant differences between the treatments. Patients treated with cisplatin/vinorelbine fared slightly better with chemotherapy alone, with an HR for disease-free survival of 1.37 (95% CI, 1.02­1.86), while those treated with cisplatin/pemetrexed did better with bevacizumab, with an HR of 0.72 (95% CI, 0.55­0.94).

Toxicities of grades 3­5 that occurred more frequently with bevacizumab than without it included hypertension in 30% of patients compared with 8%, and neutropenia in 37% compared with 33%. There were 15 deaths on treatment in the chemotherapy-alone group, and 19 deaths in the bevacizumab group.

"Four cycles of cisplatin-based adjuvant chemotherapy should remain the standard of care for patients with resected stage II and IIIA NSCLC, and is also considered an appropriate treatment option for many patients with resected stage IB NSCLC with large tumors," the authors concluded. They noted that other trials are ongoing to find additional treatments in this setting, including with immune checkpoint inhibitors. This trial, though, "provides supportive evidence that bevacizumab should not be used in the adjuvant setting for resected early-stage NSCLC."

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By Leah Lawrence

Post-traumatic stress disorder (PTSD) may be persistent or worsening in patients with cancer up to 4 years after an initial diagnosis of the disorder, according to the results of a study of South-East Asian patients published recently in Cancer.

"Our data underscore the risk of developing persistent PTSD even years after CANCER diagnosis and treatment," wrote Caryn Mei Hsien Chan, PhD, of the National University of Malaysia, and colleagues. "Approximately one-third (34.1%) of patients with cancer who are initially diagnosed with full or subsyndromal PTSD at 6 months went on to develop chronic or full PTSD at 4-years follow-up."

According to the researchers, there were no prior studies looking at the incidence of PTSD in patients with cancer that have used clinical interviews and followed patients for long periods of time. In this prospective study, they assessed both the course and predictors of PTSD in 469 consecutively recruited patients with various cancer types within 1 month of diagnosis.

Those patients with significant psychological distress underwent the PTSD module of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision at 6 months follow-up. All patients then completed the interview again 4 years later.

By combining both patients with full (13.3%) and subsyndromal (8.4%) PTSD, the researchers found about a one in five (21.7%) incidence of PTSD at the 6-month follow-up. The rate of PTSD decreased to 6.1% at the 4-year follow-up.

The researchers wrote that this high rate of PTSD was "striking" and that the fact that "Asian patients with cancer are disproportionally affected by PTSD compared with Caucasians may explain the higher rate of PTSD" reported in this study.

Of the patients initially diagnosed with full PTSD at 6-month follow-up, 22.2% had full PTSD at the 4-year follow-up; of the remaining patients, 11.1% had no PTSD, 7.4% had subsyndromal PTSD, and the rest were lost to follow-up or had died.

Overall, about one-third (34.1%) of cancer patients initially diagnosed with full or subsyndromal PTSD at 6 months went on to develop full PTSD at 4 years.

"The high rates of PTSD in our study indicate that Asian patients with cancer may be at higher risk of developing PTSD within the first 6 months of diagnosis and treatment rather than later on during the survivorship period," the researchers wrote. "Our results underline the importance of specifically screening for PTSD in cancer survivors with high levels of psychological distress, because one-third of these patients met the criteria for PTSD at the 4-year follow-up assessment."

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By Leah Lawrence

The US Food and Drug Administration (FDA) recently approved the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib for the treatment of patients with relapsed or refractory marginal zone LYMPHOMA who require systemic therapy and have had at least one prior anti-CD20 therapy.

The drug was approved based on findings from a single phase II study presented at the 2016 American Society of Hematology (ASH) Annual Meeting.
The trial included 63 patients with histologically confirmed marginal zone lymphoma who had received one or more prior therapy including at least one
CD20 monoclonal antibody. Included patients had three subtypes of disease, mucosa-associated lymphoid tissue, nodal, and splenic. All patients received ibrutinib 560 mg once daily.

Using an independent committee review, the overall response rate was 46%. The median time to response was 4.5 months. Of those patients on the trial, 3.2% had a complete response and 42.9% had a partial response. The median duration of response was not yet reached.

The most common adverse events of any grade on the trial were diarrhea, anemia, nausea, thrombocytopenia, peripheral edema, cough, arthralgia, dyspnea, and upper respiratory tract infection. The most common grade 3/4 adverse events were decreases in hemoglobin (13%), neutrophil decrease (13%), and pneumonia (10%).

Ibrutinib is also approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, including patients with 17p deletion, mantle cell lymphoma after at least one prior therapy, and patients with Waldenstrom macroglobulinemia.

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By Bryant Furlow

The indication is for newly diagnosed CML patients in chronic phase The US Food and Drug Administration (FDA) approved bosutinib (Bosulif,
Pfizer) for use as a treatment of patients with newly diagnosed chronic-phase Philadelphia chromosome­positive CHRONIC MYELOID LEUKEMIA (Ph+ CML), the drug company has announced.

Bosutinib was first approved in 2012 for treating adults with accelerated and blast-phase Ph+ CML. Pfizer¹s supplemental New Drug Application to expand the BCR-ABL tyrosine kinase inhibitor (TKI)¹s indication to include newly diagnosed adult Ph+ CML was reviewed and approved under the FDA¹s Priority Review program.

Approval was based on surrogate outcomes of the randomized multicenter, phase III BFORE trial. In this open-label study, 400 mg dosing was associated with improved rates of major molecular response at 12 months compared to imatinib (47.2% vs 36.9%) for an odds ratio [OR] of 1.55 (95% CI, 1.07­2.23; P = .02), and a 12-month complete cytogenetic response rate of 77.2% vs 66.4% for imatinib-treated patients for an OR of 1.74 (95% CI, 1.16­2.61; P = .0075). Only patients with typical Ph+ transcripts were included in the analysis. Continued approval will depend on confirmation of clinical benefit in an ongoing long-term follow-up clinical trial.

"Among patients with CML today, with the various treatment options available, it is important to recognize the unique needs of each of my CML patients and prescribe treatments that best meet those needs," said Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston, and a senior author of the BFORE trial. "The efficacy and distinct tolerability profile of Bosulif make it an important and useful treatment option for newly diagnosed CML patients."

Clinical experience with the drug thus far suggests that it is clinically effective and tolerable, noted Cortes. TKI safety profiles vary and the new option is "welcome," he said.

Grade „ 3 toxicities included increased liver enzyme values (24% vs 4% for patients in the bosutinib and imatinib study arms, respectively), thrombocytopenia (13.8% vs 5.7%), neutropenia (6.7% vs 12.1%), and diarrhea (7.8% vs < 1%).

Complete blood counts should be performed weekly during the first month of treatment and once monthly or as clinically indicated, thereafter. In rare instances, anaphylaxis and anaphylactic shock has occurred in patients treated with bosutinib, Pfizer noted. Diarrhea, abdominal pain, nausea, and vomiting can also occur, with a median time to onset of 3 days and a median duration per episode of 3 days.

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And if you have any thoughts of how this newsletter could be improved, please email me directly, at

Elaine Jesmer

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