Sylvester Experts Explain the Most Promising Advances in Cancer Research and Treatment Presented at ASCO 2022

Gilberto de Lima Lopes Jr., M.D., M.B.A

These leaders in oncology highlighted why non-small cell lung cancer remains the “poster child” for immunotherapy; how circulating tumor DNA (ctDNA) could guide treatment for colon cancer; and which presentation on breast cancer received a standing ovation at ASCO.

“In our annual review we place in perspective new studies presented at ASCO and other oncology scientific meetings,” said Gilberto de Lima Lopes Jr., M.D., M.B.A., co-chair of the Annual Oncology Update, professor of clinical medicine at the University of Miami Miller School of Medicine, and associate director of global oncology at Sylvester. “This allows our colleagues at Sylvester and other institutions to increase the speed with which new findings are translated into improvements in the care of people living with cancer in South Florida and around the world.”

The Sylvester Annual Oncology Update was held virtually and in person June 25th at the Conrad Hotel in Fort Lauderdale. Highlights include:

Hematologic Cancer

The BTK inhibitor ibrutinib, a second-line treatment, may soon be up for a promotion. “SHINE III is the first phase 3 trial showing we could move a second-line agent to first line, showing that ibrutinib in combination with chemoimmunotherapy is highly effective in people with untreated mantel cell lymphoma,” said Jorge Antunez de Mayolo, M.D., hematologist/oncologist and co-chair and presenter at the Annual Oncology Update.

Adding ibrutinib as first-line therapy to standard bendamustine-rituximab chemoimmunotherapy and rituximab maintenance therapy was associated with a median progression-free survival of 6.7 years in older people with mantel cell lymphoma. In contrast, the group treated with placebo instead of ibrutinib had a 4.4-year median progression-free survival.

Another trial presented at ASCO, the phase 1 MajesTEC-1, supports use of teclistamab as an “extremely promising, off the shelf T-cell redirecting therapy” for patients with relapsed or refractory multiple myeloma, added Dr. Antunez de Mayolo, assistant clinical professor of medicine at the Miller School. The overall response rate was 63% in this heavily pretreated group, he noted.

Colorectal Cancer

ASCO is a large conference: This year an estimated 40,000 attendees could choose among more than 200 scientific sessions, including 85 livestreamed sessions. In addition, there were more than 2,500 poster presentations. Despite the sheer size of the meeting, some research stood out.

“There was a study that got a lot of attention at ASCO because monotherapy with a PD-1 inhibitor resulted in 100% complete responders in a subtype of rectal cancer,” said Peter Hosein, M.D., associate professor of clinical medicine and co-leader of the Gastrointestinal Cancers Site Disease Group at Sylvester.

The findings are based on 14 people with MSI-H locally advanced rectal cancer, a form of the malignancy affecting about 10% of people with rectal cancer. More studies are needed, Dr. Hosein said, but now a consideration is whether PD-1 treatment could replace chemotherapy and radiation as a first-line treatment.

“I am proud to say that UM recently got accredited for the rectal cancer program as a Center of Excellence because we have a strong multidisciplinary team. So we could potentially replicate something like this in our center,” Dr. Hosein added.

Research at ASCO also highlighted growing interest in circulating tumor DNA (ctDNA) as a blood biomarker across a number of cancers. For example, the DYNAMIC study explored use of ctDNA in people with colon cancer. About half of high-risk patients in the DYNAMIC study did not have detectable ctDNA after surgery and therefore did not receive adjuvant chemotherapy. This suggests the biomarker could be used to guide therapy “and it was not detrimental” in terms of recurrence-free survival, Dr. Hosein said.

Early-Stage Breast Cancer

Another trial presented at ASCO evaluated the potential role for ctDNA in detecting minimal residual disease in high-risk, hormone-receptor positive, HER2-negative breast cancer in the late adjuvant setting. The CHiRP study linked positive ctDNA with presence of minimal residual disease, which was associated with a high risk of breast cancer recurrence with average lead time of one year.

“CHiRP is another important step in validating the role of ctDNA in the adjuvant setting,” said Frances Valdes-Albini, M.D., a breast oncologist at Sylvester and assistant professor of clinical medicine at the Miller School. Prospective studies are underway to better understand the clinical utility of ctDNA in breast cancer.

Advanced-Stage Breast Cancer

The DESTINY-Breast04 trial “achieved a standing ovation in the plenary session of ASCO,” said Elisa Krill-Jackson, M.D., a breast medical oncologist at Sylvester. The study showed that trastuzumab deruxtecan (T-Dxd) was associated with significantly longer progress-free survival and overall survival than chemotherapy.

The phase 3 study compared T-Dxd versus physician’s choice of chemotherapy in women with HER2-low unresectable and/or metastatic breast cancer. “There was marked, marked, marked improvement: almost six months in progression-free survival in HR+ women and four to five months in the entire group,” Dr. Krill-Jackson said. “This is practice changing.”

Lung Cancers

The Sylvester conference featured two presentations on lung cancer. Chukwuemeka Ikpeazu, M.D., Ph.D., M.B.A., addressed small cell lung cancer. Adding immunotherapy to chemotherapy as first-line therapy significantly prolongs overall survival and progression-free survival compared to chemotherapy alone, noted Dr. Ikpeazu, associate professor of medicine and medical oncologist at Sylvester. Also, in March 2020 the FDA approved the combination of immunotherapy Durvalumab and chemotherapy for the first-line treatment of extensive stage small cell lung cancer. Updated data at ASCO this year, he said, confirm “the regimen as a new standard of care.”

Dr. Ikpeazu added that this and other advances are very welcome by small cell lung cancer researchers. “Over the last 30 years, all we’ve been able to achieve is prolonged survival by average of three months. It’s a snail’s pace of progress,” he said.

In contrast, advances in treating non-small cell lung cancer (NSCLC) have been more rapid. Treating advanced NSCLC has made “lung cancer the poster child for precision medicine and immunotherapy,” said Estelamari Rodriguez, M.D., M.P.H., a breast, medical, and thoracic medical oncologist at Sylvester.

Now researchers are focused on moving immunotherapy to earlier phases of treatment, as adjuvant or neoadjuvant therapy. The NADIM II trial presented at ASCO, for example, added neoadjuvant nivolumab immunotherapy for three cycles to chemotherapy before surgery. The study showed a 37% pathologic complete response rate with the combination, versus 7% with chemotherapy alone. “If you have patient who is a surgery candidate, hopefully by the time they get to surgery they can have a dramatic complete pathologic response,” Dr. Rodriguez added.

Prostate Cancer

Research at ASCO supported combination treatment for prostate cancer. For example, treatment intensification for metastatic prostate cancer with abiraterone or darolutamide plus androgen deprivation therapy plus docetaxel should be the new standard of care, said Marijo Bilusic, M.D., Ph.D. Addition of abiraterone, for example, was associated in 2.5 year longer radiographic progression-free survival. Furthermore, adding darolutamide significantly prolonged survival compared to placebo added to the same regimen.

“Now we have two studies that triple therapy should be offered to metastatic prostate cancer because of a dramatic improvement in overall survival,” added Dr. Bilusic, a genitourinary medical oncologist at Sylvester.

Sarcoma

Sylvester researcher Jonathan Trent, M.D., Ph.D., was the principal investigator on a trial presented at ASCO. He and colleagues assessed the selective KIT Inhibitor PLX9486 combined with sunitinib for people with advanced gastrointestinal stromal tumors (GIST).

“This is a potent, selective targeted therapy that gets around resistance mutations with combination therapy,” said Gina D’Amato, M.D., associate professor of medicine and sarcoma medical oncologist at Sylvester. “We just opened a phase 3 trial with combination versus sunitinib alone.”

Dr. Trent also participated in the INTRIGUE trial, a phase 3 study comparing ripretinib to sunitinib in patients with GIST who were previously treated with imatinib. Ripretinib did not the meet the study’s primary endpoint of superior progression-free survival compared to sunitinib. However, ripretinib had a more favorable safety benefit and showed benefit in some subgroups.

Dr. Trent was also part of an analysis of the VOYAGER phase 3 trial looking at ctDNA in patients with advanced GIST.

Melanoma

“There was a lot of neoadjuvant therapy research presented at ASCO this year” in melanoma, said Jose Lutzky, M.D., director of cutaneous malignancy at Sylvester. The PRADO trial, for example, evaluated patients with Stage IIIB/C de novo or recurrent melanoma who received neoadjuvant ipilimumab and nivolumab and then underwent index node dissection.

Participants with pathologic complete response or near-complete response were spared total lymph node resection. “Index node status does in fact predict what you will find in the rest of the nodal basin,” Dr. Lutzky said. “Surgical morbidity was markedly reduced because many patients did not get total lymph node dissection.”

Cancer-Associated Thrombosis

Higher mortality linked to cancer-related venous-thromboembolic status demonstrates that “cancer-associated thrombosis is a marker of aggressive cancer,” said Gerald A. Soff, M.D., the new chief of the General Hematology Section at Sylvester.

Use of direct oral anticoagulant (DOACs) can be beneficial, Dr. Soff added, but they are contraindicated in patients with active gastrointestinal lesions, for example, due to elevated bleeding risk. An inappropriate question is whether a DOAC is preferable to low molecular weight heparin, for example. Rather, “The appropriate question is: In a given patient, which anticoagulant is appropriate?” he said.

To learn more about the direct roles many Sylvester experts played in ASCO 2022, read “Sylvester Stands Out at ASCO’s 2022 Annual Meeting in Chicago.”