Reprinted with permission from Cancer Watch, Vol 22, 155-156 (2013). Permission expires on Nov 28 2014

CANCER WATCH

http://www.cancerwatch.org

OCTOBER 2013

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VOLUME 22 NUMBER 10 PAGES 145-160 The mission of this magazine is to transform the expanding information on cancer research into understandable language to the curious and the informed.

News in Brief

OncoMed Initiates Phase 1b/2 Clinical Trial for Ovarian Cancer

Harris Survey: On Advanced Breast Cancer Patients

Benefit for Internal Mammary-medial Supraclavicular Node Irradiation New Imaging Tool Tracks Breast Cancer Therapy Effectiveness in Days Versatile miRNAs Choke off Cancer Blood Supply, Suppress Metastasis New Technique of Tissue Expansion for Breast Reconstruction after

Study Links Moderate Activity to Lower Breast Cancer Risk

IMPT Reduces Need for Feeding Tubes in Head & Neck Cancer Patients Swallow Exercises in Head&Neck Cancer Patients Receiving Radiation Intralesional PV-10 in Advanced Melanoma

Findings of Critzotinib Clinical Trials

In French "Real-Life" Practice, Similar Findings to Critzotinib Trials

Genetic variants linked to esophageal cancer and Barrett's esophagus

Misuse of Radiation Therapy In Prostate Cancer Patients

Insights into DNA Repair Process May Spur Better Cancer Therapies

Glossary

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PV-10 in Advanced Melanoma: High Response Rates, Evidence of Systemic Response

Confirmation of high clinical response rates and further evidence of systemic effects for intralesional PV-10 (Rose Bengal 10% disodium) emerged from

an updated analysis of an interna- tional, multicenter phase 2 study among 80 patients with advanced melanoma. In addition, the side

effect of blistering appears to corre- late with better responses and sug- gests immune activation, according to Sanjiv S. Agarwala, MD, professor

CANCER WATCH, VOL. 22, OCTOBER 2013 155

of medicine at Temple University, Philadelphia, PA.*

Up to 10 cutaneous or subcutaneous target lesions were injected with intra- lesional PV-10 in patients with stage IIIB-IV melanoma, Dr. Agarwala said in a 2013 European Cancer Congress poster presentation. The lesions were reinjected if necessary at weeks 8,
12, and 16. Up to 2 additional cuta- neous or subcutaneous lesions were left untreated to assess bystander response. The primary endpoint was best overall response rate in up to 10 target lesions.
Dr. Agarwala reported that in this popu- lation of patients who were refractory to a median of 6 prior interventions, best overall response was 51% (26% complete, 25% partial). The amount of tumor burden accessible to PV-10 injection was prognostic for outcome, with both magnitude and duration of response inversely related to untreated tumor burden. For patients in whom all lesions (except for up to two untreated bystander lesions) could be treated, the best overall response rate was 63%. In subjects where all disease was treated, the complete (50%) plus partial (21%) rate further increased to 71%. The clini- cal response rate (complete response
plus partial response plus stable disease
[locoregional disease control]) was
82% in this subgroup.

In patients who experienced blister- ing of target lesions, the rate for com- plete plus partial responses (91%) was significantly higher than among those without blistering (54%, P 0.001). "Patients get very concerned when blis- tering develops because they feel it may be indicating an infection, but now I can tell them that it's actually a good thing, maybe correlating with a benefit and secondly signaling that their immune system is activating." He added, "The principle is that this agent has a local chemoablative effect, one where we believe it enters into lysosomes caus- ing local necrosis and sometimes blis- tering of the lesion, indicative of the observed systemic effect in 'bystander' lesions which we think is immunologi- cally mediated," Dr. Agarwala said. The
54% complete plus partial response rate in uninjected "bystander" lesions sup- ports that notion.
Dr. Agarwala speculated on potential uses of PV-10, should its benefits in phase 3 testing currently being planned persist and lead to ultimate approval. His surgical colleagues, he said, are inter- ested in the possibility of presurgical
PV-10 injections turning unresectable lesions into resectable ones and/or stimulating the immune system to lower the odds of recurrence.
Two groups of patients would be prime candidates, Dr. Agarwala continued: patients who are refractory to all other therapies and who have injectable dis- ease, and patients who have inject- able lesions but who are not eligible for systemic therapy (e.g., the elderly or those with comorbidities). Combin- ing PV-10 with other therapies such as ipilimumab or nivolumab would be an attractive option. He added, "Of course, all of these need to be tested in clinical trials."