Shreyaskumar R. Patel, MD: Targeted Therapies Influencing Treatment Options

How has the availability of targeted therapies influenced treatment options for patients with leiomyosarcoma?

Leiomyosarcoma originating in the gastrointestinal tract, now named gastrointestinal stromal tumors, are a poster child of targeted therapy for solid tumors. We have an activating mutation, we know what the driver is for tumor regenesis, and we have an effective inhibitor of that pathway. Therefore, the longevity of patients with even advanced and metastatic gastrointestinal stromal tumors has changed with the availability of several different kinase inhibitors.

One would like to mimic this in several other subsets, but unfortunately we are not quite there yet. The only targeted therapy from a conventional or traditional targeted therapy standpoint that is available for this patient population today is pazopanib, which this patient was already on. I think there are attempts at trying to find newer targets and investigate inhibitors off those pathways to see if we can broaden the spectrum of tumor types and patients who would be eligible for targeted therapies. We have not been as successful as we would like to.

CASE: Soft-Tissue Sarcoma (Part 1)

Rachel F is a 58-year-old school teacher from Roanoke, Virginia. Her medical history is notable for mild hypertension and total knee replacement in 2011

• In March of 2013, she presented to her PCP with abdominal fullness and distension of several months’ duration; physical exam showed mild abdominal discomfort on palpation; she denied any recent weight loss
• Initial abdominal sonography was inconclusive; subsequent CT scan showed a heterogeneously enhancing retroperitoneal mass along segment I of the inferior vena cava (IVC) and central necrosis
• She underwent contrast-enhanced CT with coronal and sagittal reconstructions, which showed encasement of the aorta and multiple hepatic metastases
• CT guided biopsy of the mass showed leiomyosarcoma that was immunohistochemically positive for desmin, smooth muscle actin, and vimentin, with a high proliferative rate (Ki67 > 60%)
• She underwent chemotherapy with gemcitabine and docetaxel for a total of 6 cycles, and experienced a minor response. Therapy was discontinued however, in November 2013 due to cumulative toxicity

Follow-up CT scan in January 2014 showed progression at multiple sites; at the time of follow up, her ECOG performance status was 1, with renal and hepatic function within normal limits

• She underwent six cycles of chemotherapy with anthracycline and dacarbazine, and her disease stabilized

In September of 2014 she returns for follow-up, unable to work with increasing fatigue and abdominal pain, and her CT scan was consistent with progressive disease

• She received treatment with pazopanib at 800 mg daily for metastatic disease
• Patient tolerated the treatment well, with mild fatigue and diarrhea, and her symptoms improved

After 4 months of therapy, she presents with worsening abdominal pain and declining performance status

• CT showed extensive progression of the primary tumor and hepatic metastases
• At progression, CBC, liver, and renal function were within normal limits, ECOG performance status was 2