Chemotalk Newsletter

Chemotalk Newsletter, Vol. 114 October 1, 2017

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Much happening, treatment-wise, beginning with...

 

NIVOLUMAB NEW STANDARD FOR ADVANCED, HIGH-RISK RESECTED MELANOMA

By Leah Lawrence

Nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with stage III/IV MELANOMA at high risk for recurrence, according to results of the CheckMate 238 study (abstract LBA8_PR) presented at the 2017 European Society for Medical Oncology (ESMO) Congress in Madrid. Ipilimumab is currently the US Food and Drug Administration (FDA)-approved standard of care treatment for resected stage III melanoma in the United States.

"The results clearly show that relapse-free survival is more favorable with Nivolumab," investigator Jeffrey Weber, MD, deputy director, Perlmutter Cancer Center, NYU Langone Health, said in a press release. "The majority of patients had higher risk disease than in most prior adjuvant melanoma trials, which makes the findings even more encouraging."

The study included 906 patients aged 15 or older with complete resection of stage IIIb (34%), stage IIIc (47%), or stage IV (19%) melanoma. They were randomly assigned to Nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses, then every 12 weeks for up to 1 year.

The trial was stopped early after clear evidence of a benefit with Nivolumab. At a follow-up of 18.5 months, treatment with Nivolumab resulted in a 35% lower risk for recurrence compared with ipilimumab (hazard ratio, 0.65; 95% CI, 0.51­0.83). The 18-month recurrence-free survival was 66.4% compared with 52.7% for ipilimumab (P < .0001).

There were similar results across prespecified subgroups of patients including analyses of PD-L1 expression, which showed hazard ratios in favor of Nivolumab.

"A previous trial found that ipilimumab had a significant relapse-free and overall survival advantage compared to placebo," Weber said. "CheckMate
238 shows that Nivolumab is superior to ipilimumab, so extrapolating these results, Nivolumab is far better than no adjuvant treatment for high-risk melanoma. It is also much less toxic than ipilimumab.

Indeed, patients assigned to Nivolumab had improved safety. Treatment-related grade 3/4 adverse events occurred in 14% of patients treated with nivolumab compared with 46% of patients assigned ipilimumab. Only 10% of patients assigned Nivolumab stopped treatment due to adverse events compared with 43% of those assigned ipilimumab.

"The results of CheckMate 238 are very exciting," said professor John Haanen, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, commenting on the results of the study. "They show for the first time that an anti­PD-1 drug is superior in the adjuvant setting and because of its lower toxicity Nivolumab is much easier to give than ipilimumab."

The results of the study were published simultaneously in the New England Journal of Medicine.

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HLA-MISMATCHED MICROTRANSPLANT IN OLDER AML PATIENT YIELDS GOOD RESULTS

By Dave Levitan

HLA-mismatched microtransplant offers good complete remission (CR) rates in older patients with ACUTE MYELOID LEUKEMIA (AML), according to a new study.

"Older patients („ 60 years) with AML have a lower CR rate and higher mortality after standard treatments because of intrinsic drug resistance related to poor-risk cytogenetics, as well as unique biology, with different molecular drivers evidence compared with younger patients," wrote senior study author Hui-Sheng Ai, MD, of the Affiliated Hospital of the Academy of Military Medical Sciences in Beijing, and colleagues. Earlier studies have shown that infusion of granulocyte colony stimulating factor­mobilized HLA-mismatched peripheral blood stem cells (microtransplant) can improve outcomes.

The new study included 185 patients with AML with a median age of 67 years. They were divided into four age groups: 60 to 64 years (69 patients),
65 to 69 years (47 patients), 70 to 74 years (43 patients), and 75 to 85 years (26 patients). They received HLA-mismatched donor cell infusions and induction CHEMOTHERAPY, and those that achieved CR received postremission therapy; the results were published in JAMA Oncology.

In the full cohort, the CR rate was 74.6%. The rate did not differ significantly between the 4 age groups, at 75.4%, 70.2%, 79.1%, and 73.1%, respectively. The CR rate was lower in a group of 90 patients considered high risk (66.7%) vs those in the standard-risk group (82.1%; P = .02).

Overall, the median time to neutrophil recovery was 12 days after induction CHEMOTHERAPY, and the median time to platelet recovery was 14 days; again, there were no differences between the age groups. There were 11 severe infections (8.0% of the 138 patients who achieved CR) and 3 cases of organ failure (2.2%).

The median overall survival (OS) among those who achieved CR was 14 months; in the 4 age groups, the median OS was 16, 14, 13, and 10 months, respectively. The oldest age group had a 1-year OS rate of 51.7%, which was significantly lower than that of the younger 3 groups (87.7%, P = .004; 85.8%, P = .008); 77.8%, P = .04). The youngest group's 2-year OS rate of 63.7% was higher than the rates of the older 2 age groups (34.2% and 14.8%).

Only two patients in the study demonstrated stable full donor chimerism, and three had mixed chimerism. Two patients (1.1%) had severe graft-vs-host disease; both failed to respond to treatment and died of multi-organ failure.

The authors wrote that the CR and OS outcomes are better than that seen with standard care in older AML patients. The study is limited by lack of randomization; however, such a study is difficult to conduct, especially in older patients.

"Clinical results suggest that [microtransplant] is a safe, practical, and reproducible therapy in older patients newly diagnosed as having AML," they concluded.

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FDA APPROVES FIRST BIOSIMILAR FOR CANCER TREATMENT

By Leah Lawrence

Mvasi has been approved as a biosimilar to Avastin, but not as an interchangeable product.  The US Food and Drug Administration (FDA) has approved Mvasi (bevacizumab-awwb, Amgen) as a biosimilar to Avastin (bevacizumab, Genentech) for the treatment of multiple types of cancer including COLORECTAL, LUNG, BRAIN, KIDNEY AND CERVICAL CANCERS. This approval is the first biosimilar approved for the treatment of cancer in the United States.

The approval was based on a review of data that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Mvasi is biosimilar to Avastin.

The FDA noted that Mvasi has been approved as a biosimilar to Avastin but not as an interchangeable product.

"Bringing new biosimilars to patients, especially for diseases where the cost of existing treatments can be high, is an important way to help spur competition that can lower healthcare costs and increase access to important therapies," FDA Commissioner Scott Gottlieb, MD, said in a press release.

"We'll continue to work hard to ensure that biosimilar medications are brought to the market quickly, through a process that makes certain that these new medicines meet the FDA's rigorous gold standard for safety and effectiveness."

The specific indications outlined by the FDA include:

Metastatic Colorectal Cancer

  • In combination with intravenous 5-fluorouracil­based CHEMOTHERAPY for
    first- or second-line treatment. Not indicated for the adjuvant treatment of surgically resected colorectal cancer.
  • In combination with fluoropyrimidine/irinotecan- or fluoropyrimidine/oxaliplatin-based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product­containing regimen. Not indicated for adjuvant treatment of surgically resected cancer.
  • Nonsquamous Non­Small-Cell Lung Cancer
  • In combination with carboplatin and paclitaxel for the first-line treatment of unresectable, locally advanced, recurrent or metastatic disease.

Glioblastoma

  • With progressive disease following prior therapy, based on improvement in objective response rate. No data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab products.

Metastatic Renal Cell Carcinoma

  • In combination with interferon alfa.

Cervical Cancer

  • For persistent, recurrent, or metastatic disease, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.

The label for Mvasi contains a boxed warning to alert healthcare professionals and patients about increased risk for gastrointestinal perforation, surgery and wound healing complications, severe or fatal pulmonary, gastrointestinal, and central nervous system and vaginal hemorrhage.

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And finally, just in case health care isn't political enough...

HOUSE GOP DEMANDS DATA ON FUNDING FOR ITALIAN CANCER RESEARCH AGENCY

by Todd Shepherd

The House Science, Space, and Technology Committee is demanding copies of contracts and grants between the Department of Health and Human Services and a cancer research institute in Italy that Republicans say provided controversial and biased research that has led to incorrect decisions about the safety of some products.

The federal government has provided about $92 million in grants to an Italian researcher, the Ramazzini Institute, since 2009, and about $2 million in other contracts, according to the committee's letter to HHS, which cited media reports.

But Ramazzini's transparency and findings have been questioned. For example, a 2012 decision by Ramazzini saying that the artificial sweetener sucralose was a cancer-causing agent was directly contradicted in May by the European Food Safety Authority.

Wednesday's committee letter also outlined an incident from 2010 in which the EPA decided to abandon any reliance on studies from Ramazzini on methanol, and noted that the EPA's National Toxicology Program cited concerns about elements of Ramazzini's methodologies.

Issues like these are what prompted the science committee to ask HHS to outline all the funding from the National Institute of Environmental Health Sciences (NIEHS) to Ramazzini. The committee made a similar request in March, but it said documents received so far from HHS "only raised new questions."

The committee is essentially asking HHS to start over in responding to a request for documentation on how some grants and contracts were awarded to the research institute. But the new request also indicated that some of the grants appear to have been made informally, and asked HHS if those distributions were made according to competitive bidding rules, or if they were sole-source contracts.

"Specifically, the Committee is concerned about the informal nature of the agreements and contracts between NIEHS and RI, the lack of evidence of competition in contracting, and the unjustified continuation of the contracts for 17 years," Committee Chairman Lamar Smith, R-Texas, wrote to HHS Secretary Tom Price on Wednesday.

The committee letter said lawmakers have "significant concerns about whether NIEHS was operating within the rigorous confines" of federal regulations about awarding contracts, and asked HHS to supply numerous grant and contract documents as well as all communications between NIEHS staff and Ramazzini related to those grants.

The free-market think tank E&E Legal currently has a FOIA lawsuit against NIEHS to obtain contracts with Ramazzini.

The Ramazzini inquiry by the House committee comes as the political battles over science have intensified between Republicans who say the government has relied on non-transparent science for too many years, and Democrats who accuse Republicans of being anti-science by not incorporating as much data as possible, or simply ignoring scientific data altogether.

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NEXT ISSUE: November 1, 2017

 

And if you have any thoughts of how this newsletter could be improved, please email me directly, at Elaine@elainejesmer.com.

Elaine Jesmer

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