For many years, people with advanced cancer who turn to Cancer Commons have benefitted from working with Chief Scientist Emma Shtivelman, PhD. Here, she shares three patients’ stories.
Curious Dr. George: You have helped many hundreds of patients with advanced cancer to feel valued, to better understand their disease and their clinical situation, and to explore their options. Will you please share with our readers a few de-identified examples of patients who benefited from your assistance?
Emma Shtivelman, PhD: In my years of work with numerous advanced cancer patients, I have experienced many sad developments—as expected when dealing with advanced cancers—but also some moments of satisfaction with the results of my efforts. Here are a few examples:
Case 1: A 64-year-old woman came to us with triple-negative breast cancer metastatic to her lung and significant thoracic lymphadenopathy. She had been treated with two lines of chemotherapy and stereotactic body radiation therapy (SBRT) to her lung tumors, with poor response. Cancer Commons suggested and facilitated mutational analysis through our partner Tempus, which showed a TP53 mutation and RB1 copy number loss, as well as amplification of several genes, including PD-L1 and PD-L2. PD-L1 protein was, however, negative in immunohistochemistry (IHC) testing.
At this time, a single scientific publication documented a high rate of durable responses to anti-PD-1 drugs in solid tumors that have amplification of PD-L1/L2 (a very rare event), even in the absence of detectable PD-L1 protein. Based on these results, I suggested to the patient that she seek enrollment in a clinical trial known as DART, which offers the immune checkpoint drug nivolumab with or without the drug ipilimumab for rare tumors and includes a patient cohort specifically for people with PD-L1 amplification.
The patient started treatment with nivolumab and had a remarkable response, with resolution of her lung tumors and significant reduction of her lymphadenopathy. Now, more than two years later, she is maintaining this remarkable response with some slightly enlarged mediastinal lymph nodes as the only sign of cancer.
Case 2: I began working with a 58-year-old woman with metastatic endometrial cancer after she had received three lines of chemotherapy, followed by recurrence each time. Next-generation sequencing (NGS) analysis of tumor DNA detected loss of function mutations in ARID1A and ATM, as well as amplification of HER2.
At this time, the U.S. Food and Drug Administration (FDA) had approved the drugs pembrolizumab and lenvatinib as treatment for endometrial cancer, and this was planned as the next line of treatment for her. I suggested she also consider treatment in two trials, with the more preferable one offering the drug ceralasertib (an ATR inhibitor) in combination with trastuzumab deruxtecan (an antibody drug conjugate to HER2 with so-far unsurpassed activity in HER2+ breast cancers). Ceralasertib has shown significant activity in ARID1A-deficient endometrial cancer patients. This combination would have been a perfect fit for the patient based on DNA alterations present. The second trial I found offered ceralasertib as monotherapy.
Unfortunately, the first trial never responded to the patient’s email or calls, but she successfully enrolled in the second trial, with ceralasertib as monotherapy. Treatment for 5 months led to a 75% decrease in her serum cancer markers and a 45% decrease in tumor burden by RECIST criteria. Her response is ongoing.
Case 3: A 69-year-old woman was diagnosed with recurrence of HPV-related anal squamous carcinoma. She had initially been diagnosed with localized anal cancer 5 years earlier, which was treated with radiation and chemotherapy. In subsequent years she experienced 4 oligometastatic recurrences in lungs and one in the rectum, which were treated with surgeries, radiation, and chemotherapy. In 2019 three metastatic tumors were detected in her lungs.
I suggested some trials—including one known as Hestia—offering HPV E6/7 specific T cells (T cells isolated from peripheral blood and stimulated with HPV peptides). The patient has now undergone treatment in Hestia with a complete response, and remains disease-free almost 3 years later. Apparently, she was the only patient who had a durable response to this trial treatment.
Dr. Shtivelman can be reached at firstname.lastname@example.org.
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