The vastly improved outlook for patients with chronic lymphocytic leukemia (CLL) was named the American Society of Clinical Oncology's inaugural "Cancer Advance of the Year."
The vastly improved outlook for patients with chronic lymphocytic leukemia (CLL) was named the American Society of Clinical Oncology's inaugural “Cancer Advance of the Year.” Specifically, the country's leading professional oncology organization is recognizing the approval of four new therapeutic options for CLL over the past two years: Gazyva (obinutuzumab), Imbruvica (ibrutinib), Arzerra (ofatumumab) and Zydelig (idelalisib).
The announcement was made as part of ASCO’s release of its annual update on oncology treatment advances: Clinical Cancer Advances 2015: ASCO's Annual Report on Progress Against Cancer.
“These new therapies fill an enormous need for thousands of patients living with CLL,” said Gregory Masters, ASCO expert and co-executive editor of the report, in a statement. “For many older patients, especially, these drugs essentially offer the first chance at effective treatment, since the side effects of earlier options were simply too toxic for many to handle.”
The immunotherapies (Gazyva) and ofatumumab (Arzerra) are approved in the frontline CLL setting, while the small-molecule inhibitors Imbruvica and Zydelig are approved for resistant/relapsed CLL.
The first of these four agents approved over 2013 and 2014 was the anti-CD20 agent Gazyva . In November 2013, the FDA approved the drug in combination with chlorambucil as a first-line treatment regimen for patients with CLL based on data from the phase 3 CLL11 trial. In the study, the Gazyva/chlorambucil combination significantly reduced the risk of progression by 84 percent, when compared with chlorambucil alone.
In December 2014, the FDA updated the label for Gazyva plus chlorambucil to include data from stage 2 of the CLL11 study, which detailed an unprecedented 11.8-month improvement in progression-free survival (PFS) compared with Rituxan (rituximab) plus chlorambucil as a frontline treatment for patients with CLL (26.7 months compared with 14.9 months.
The next new option approved for patients with CLL was the BTK inhibitor Imbruvica in February 2014. The FDA approved the agent for patients with CLL who have received at least one previous therapy. The decision was based on data from 48 patients enrolled in the single-arm phase 1b/2 PCYC-1102-CA study. At a median 15.6-month follow-up for this group, single-agent Imbruvica produced an overall response rate (ORR) of 58.3 percent (all partial responses) with a duration of response of up to 24.2 months.
The most common grade 3/4 nonhematological adverse reactions were pneumonia, hypertension, dehydration, atrial fibrillation, and sinusitis. Additionally, Imbruvica-related grade 3/4 cytopenias were reported in 35 percent of patients.
In July 2014, the FDA expanded the approval of Imbruvica to include the treatment of patients with CLL who harbor a 17p deletion, based on findings from the phase 3 RESONATE trial. In RESONATE, Imbruvica lowered the risk of progression by 75 percent in patients with CLL who harbored a 17p deletion and by 78 percent in the full population of the study when compared with Arzerra.
The anti-CD20 agent Arzerra, which received a new indication in April 2014, marked the third new CLL treatment option made available over the past couple of years. The indication is for Arzerra plus chlorambucil for previously untreated patients with CLL who are considered inappropriate for treatment with the chemotherapy fludarabine. The FDA first approved Arzerra in October 2009 for the treatment of patients with CLL who no longer respond to chemotherapy.
The new approval was based on results from the phase 3 COMPLEMENT 1 trial, in which Arzerra and chlorambucil demonstrated a 9.3-month improvement in PFS compared with chlorambucil alone. The ORR with the combination was 82 percent versus 69 percent with chlorambucil alone.
Grade 3/4 adverse events occurred in 50 percent of patients treated with ofatumumab compared with 43 percent in the chlorambucil monotherapy arm. The most common grade 3/4 toxicity was neutropenia, which occurred in 26 percent of patients treated with Arzerra compared with 14 percent for chlorambucil alone. Grade 3/4 infusion-related adverse events were reported in 10 percent of patients treated with Arzerra compared with none for those receiving chlorambucil alone.
And rounding out the impressive 2013/2014 breakthroughs in CLL care was the July 2014 approval of the PI3K-delta inhibitor Zydelig in combination with Rituxan for patients with high-risk relapsed or refractory CLL. The approval was based on the phase 3 Study 116 trial, in which the addition of Zydelig to Rituxan improved overall survival by 72 percent and PFS by 82 percent versus placebo and Rituxan.
In a statement on the naming of these CLL breakthroughs as the Cancer Advance of the Year, ASCO President Peter P. Yu, MD, said, “This has truly been a banner year for CLL and for clinical cancer research as a whole. Advances in cancer prevention and care, especially those in precision medicine, are offering stunning new possibilities for patients.”
ASCO’s Annual Report on Progress Against Cancer, now in its 10th year, was published online in the Journal of Clinical Oncology. The 2015 report was developed by an editorial board of 18 experts representing a wide spectrum of oncology specialties. Beyond announcing the top advancement in cancer, this year’s report also includes a look back at the last 10 years in oncology and a look forward at projected trends for the next decade, as well as sections on the top research advances from the past year and promising early advances in rare cancers.
[Read the report here.]