marked survival improvement for Stage IVs reported with immunotherapy

[Lani]

various cancer types--just got back from AACR. Another type of immunotherapy led to "cures" in a substantial number of metastatic patients of different cancer types. Things are happening (not quickly enough, but happening!)

Regimen May Hike Survival in Advanced Cancer
By Charles Bankhead, Staff Writer, MedPage Today
Published: April 05, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, Nurse Planner





CHICAGO -- Patients with advanced and metastatic cancers had "unexpected 5-year survival" when treated with an inexpensive maintenance immunotherapy that boosted levels of natural killer cells, investigators reported here.

Patients with a variety of stage IV cancers had substantially better overall survival when they received the combination of interleukin-2 and 13-cis retinoic acid after chemotherapy that produced stable disease or better response.

As compared with historical survival data, the regimen was associated with a twofold or greater improvement in 5-year survival.

The maintenance therapy was well tolerated, including no grade 3-4 toxicity, Francesco Recchia, MD, reported at the American Association for Cancer Research meeting.

"The administration of IL-2 and retinoic acid results -- with a modest toxicity profile -- in a sustained improvement in natural killer (NK) cells, a decrease in vascular endothelial growth factor (VEGF), and unexpected 5-year survival rates," Recchia, of Ospedale Civile di Avezzano in Avezzano, Italy, said during a press briefing at the AACR meeting.

More than a decade ago, Recchia and colleagues found that the maintenance regimen improved immunologic parameters associated with more favorable prognosis in advanced cancer (Clin Cancer Res 2011; 7: 1251-1257). At least two patients who had partial responses to chemotherapy subsequently had complete responses during maintenance therapy.

The investigators took an interest in the immunotherapeutic doublet because of what they perceived as an unmet need for an inexpensive, minimally-toxic maintenance therapy to prolong responses achieved with conventional chemotherapy. The 18-patient initial clinical experience has since grown into a 500-patient study involving patients with advanced-stage solid tumors.

The IL-2/13-cis retinoic acid combination had clinical appeal for several reasons: IL-2 has no known cross-resistance with chemotherapy and improves disease-associated lymphocytopenias, which are associated with poor prognosis. The retinoid has immunodulatory properties and potential synergy with IL-2.

Patients eligible for the maintenance regimen had achieved stable disease or objective response (complete or partial) to chemotherapy. They self-administered the drugs (subcutaneously for IL-2, orally for 13-cis-retinoic acid) five days a week for two 3-week courses, followed by a week off therapy. Treatment continued for a year, followed by intermittent therapy for five years or until disease progression.

The primary objective was to determine whether the maintenance therapy increased levels of NK cells and reduced levels of VEGF. Secondary endpoints were disease-free survival (DFS), overall survival, and toxicity.

Investigators assessed NK levels, VEGF levels, tumor response, and toxicity every four months.

During a median follow-up of five years, the average NK level increased from 309 pg/mm3 to 579 pg/mm3 (P<0.001) and the mean VEGF level declined from 520 pg/mm3 to 150 pg/mm3 (P<0.001).

The most common toxicity was grade 2 cutaneous adverse events, which occurred in 20% of patients, and grade 2 fever in 13%.

The 15-year DFS was 32.6% and overall survival was 36.8%.

Recchia compared 5-year overall survival for selected tumor types with historical data for advanced cancer from the NCI Surveillance, Epidemiology, and End Results program. Improved survival was observed for:

Breast cancer: 42.7% versus 23.3%
Lung cancer: 26.4% versus 3.6%
Colorectal cancer: 43.6% versus 11.7%
Renal cancer: 23% versus 11%
Noting that bevacizumab (Avastin) is used increasingly as maintenance therapy, Recchia said the estimated monthly cost for the angiogenesis inhibitor is $1,700 as compared with $304 for the IL-2/retinoid regimen.

Recchia had no relevant disclosures.

Primary source: American Association for Cancer Research
Source reference:
Recchia F, et al "Extended phase II study of maintenance immunotherapy in advanced cancer" AACR 2012; Abstract 5366.

This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
This maintenance study in 500 patients with advanced solid tumors found improved overall survival compared with historical survival rates for those receiving interleukin-2 plus 13-cis retinoic acid following a response to chemotherapy.
Note that natural killer cells increased and levels of vascular endothelial growth factor decreased, which were the primary endpoints of the study.

[Ellie F]

Thanks Lani
Quite spectacular results here!
Ellie

[SoCalGal]

just copied the info to discuss with my docs...thanks much, Lani.

[ElaineM]

I love this idea !!

[chrisy]

Wow. Good stuff!

[KDR]

Stunning!
Karen

[MJo]

A dear friend is getting immunotherapy for pancreatic cancer. Fingers crossed.

[Mtngrl]

A doctor friend (who knows I'm Stage IV) took me aside last September and said, "you have an immune problem and a hormone problem. There's no reason to think you can't solve those problems." It just makes sense to go at it from this direction. The wonder is not that some of us get cancer; it's that we don't all have it.