ASCO Highlights: Pazopanib in ovarian cancer; combination immunotherapy for melanoma

In a press briefing on Saturday, ASCO highlighted important advances in treatment for multiple aggressive cancers, and new insight on HPV related cancer risk.


Maintenance therapy with pazopanib delays relapses in women with advanced ovarian cancer

A phase III clinical trial in women with advanced ovarian cancer finds that treatment with the oral targeted drug pazopanib (Votrient) following initial successful chemotherapy extends disease-free survival by an average of 5.6 months, compared to placebo.

New immunotherapy combination appears promising for metastatic melanoma

A proof-of-principal phase II study shows that the white blood cell booster GM-CSF (Sargramostim, Leukine) added to an increased dose of the immunotherapy ipilimumab (Yervoy) extends survival for patients with metastatic melanoma. More than two-thirds of patients were alive after one year of combination therapy vs. half of those treated with ipilimumab alone, a significant advance for metastatic melanoma. Interestingly, the combination also appears to be safer for patients than ipilimumab alone — GM-CSF decreased some of the serious side effects of ipilimumab.

In this study, 245 patients with metastatic melanoma who had undergone up to one prior treatment were assigned to receive ipilimumab plus GM-CSF or ipilimumab alone (at a dose of 10 mg/kg). The median follow up time was 13.3 months. Tumor shrinkage rates were comparable in both arms (11-14 percent) but the overall survival rate was longer in the combination treatment arm: one year after the start of therapy, 68.9 percent of patients who received the combination were alive, compared to 52.9 percent of patients who received ipilimumab alone. Patients who received the combination treatment had a 35 percent lower risk of dying compared with those that received ipilimumab alone.

Investigational anti-PD-1 antibody nivolumab shows strong anti-cancer activity in patients with advanced melanoma

Pazopanib is an oral drug that blocks several targets involved in the growth of tumors and their blood vessels (angiogenesis). In the study, 940 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer were randomly assigned to receive pazopanib or placebo daily for 24 months. All patients had prior surgery and five or more rounds of chemotherapy that successfully prevented the disease from worsening. Patients were followed for 24 months, on average. The median time to disease worsening (progression-free survival) in the pazopanib and placebo group was 17.9 and 12.3 months, respectively.Long-term follow-up results from an expanded phase I study indicate that nivolumab produces long-lasting responses in patients with stage IV melanoma. Historical response rates to immunotherapy drugs in advanced melanoma are five to 10 percent, but 30 percent of patients experienced tumor shrinkage in this study.

Early study suggests selumetinib may be the first active drug for advanced melanoma of the eye

Final analysis of data from a phase II cross-over study in patients with metastatic melanoma of the eye finds that selumetinib resulted in tumor shrinkage in half of all patients treated and a duration of disease control more than twice that achieved with temozolomide (Temodar). While temozolomide is a long-time standard therapy for skin melanoma, it has little effect in most patients with skin or eye melanoma, and alternate treatment options are urgently needed. There is no known effective systemic therapy for metastatic melanoma of the eye. Indeed, of the 157 patients treated on eight different clinical trials testing potential new therapies for this cancer, including chemotherapy, targeted therapy and immunotherapy, over the past decade, only two patients experienced major tumor shrinkage.

In this study, 98 patients with metastatic melanoma of the eye were randomly assigned to receive selumetinib or temozolomide, with 48 receiving selumetinib and 50 receiving temozolomide. Forty-seven percent of patients had Gna11 alterations in their tumors, thirty-seven percent had Gna11 alterations, and the rest did not have alterations in either of those genes. Patients whose disease worsened on temozolomide were permitted to cross over to selumetinib. Fifty percent of patients experienced tumor shrinkage, with 15 percent achieving major tumor shrinkage in the selumetinib group. None achieved significant shrinkage in the temozolomide group.

Partners of patients with HPV-related oropharyngeal cancer do not have increased levels of oral HPV infection

In this study, 107 patients were treated with five different doses of nivolumab. All patients had disease that worsened despite prior standard systemic therapies — 25 percent had three or more prior therapies and 63 percent had two or more. Overall, 33 out of 107 (31 percent) of patients experienced tumor shrinkage of at least 30 percent and responses were seen at all doses. The estimate for survival at two years was 43 percent. The median overall survival across all doses was 16.8 months; 20.3 months for the dose chosen for study in subsequent clinical trials. While this is an early-phase study, and the results cannot be directly compared to those with other drugs, the results are striking, with median overall survival exceeding that seen with the most recently approved melanoma drugs.While many spouses of patients diagnosed with human papilloma virus (HPV)-positive oropharyngeal cancer (OPC) have anxiety over their own HPV-related cancer risk, a new study finds that spouses were no more likely to test positive for oral HPV infection than people in the general population. The Human Oral Papillomavirus Transmission in Partners over Time (HOTSPOT) study is the first large study to examine oral HPV infection among patients with HPV-caused oropharyngeal cancer and their spouses. This study confirms that couples who have been together for several years do not need to change their intimacy or sexual behavior because of the cancer diagnosis.

Cetuximab is superior to bevacizumab in combination with FOLFIRI chemotherapy for first-line treatment of metastatic colorectal cancer

The German phase III clinical trial FIRE-3 reports that first-line cetuximab (Erbitux) plus FOLFIRI chemotherapy (folinic acid, fluorouracil, irinotecan) offers a roughly four-month survival advantage for patients with metastatic colorectal cancer, compared with bevacizumab (Avastin) plus FOLFIRI. The targeted drugs cetuximab and bevacizumab, both in combination with chemotherapy, are approved and commonly used as initial therapy but, until this study, it has been unclear which approach is better for patients with non-mutated forms of the KRAS gene.

In the study, 592 patients with non-mutated (wild-type) KRAS metastatic colorectal cancer were randomly assigned to first-line therapy with FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab. Overall response rate favored FOLFIRI plus cetuximab, but reached the level of significance only in assessable patients. These patients (n=526) were required to have at least one imaging procedure after baseline. The median time to disease progression (progression-free survival) was nearly identical in the two arms (10.0 vs. 10.3 months), but the overall survival was markedly longer in the cetuximab arm (28.7 months) compared to the bevacizumab arm (25.0 months).

HPV DNA was detected in 66 percent of HPV-OPC patients at diagnosis but only 7 percent of those patients still had oral HPV infection one year later, after having gone through cancer treatment. The overall prevalence of oral HPV among partners was 7.2 percent. The prevalence among the 75 female partners was 5 percent, which is comparable to the prevalence among women in the general population (4 percent, based on previously published data). The prevalence among the small number of male partners assessed in this study was also similar to that among men in the general population, though higher than in the female population. HPV16, the subtype responsible for most cases of HPV-OPC, was detected in 54 percent of HPV-OPC patients but in only 2.7 percent of female partners and in none of the male partners. Taken together, the researchers stated that the findings provide reassurance for both female and male partners that their risk of developing HPV-OPC remains low. No pre-cancers or cancers were detected in the 64 percent of partners that underwent a visual oral exam.


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