Top Takeaways from ASCO: Gastrointestinal cancer

Research demonstrates positive responses with immunotherapy, chemotherapy combinations

CHICAGO — Encouraging data on using immunotherapy and a new chemotherapy combination to treat gastrointestinal cancers were revealed at the ASCO annual meeting.

Positive results were seen with pembrolizumab (Keytruda, Merck) in patients with both colorectal and gastric cancer, and nivolumab (Opdivo, Bristol-Myers Squibb) offered benefits to those with hepatocellular carcinoma.

“There is a lot of excitement around immunotherapy,” Tanios Bekaii-Saab, MD, professor of medicine and pharmacy, and section chief of gastrointestinal oncology, The Ohio State University, Columbus, told Healio.com. “This is the ‘flavor du jour.’”

When administered together, trastuzumab (Herceptin, Genentech) and lapatinib (Tykerb, Novartis) improved outcomes in patients with colorectal cancer and HER overexpression.

“[These findings] have the potential to change practice,” Steven R. Alberts, MD, professor of oncology and chair of the medical oncology division, Mayo College of Medicine, Minnesota, who specializes in gastrointestinal cancers, told Healio.com.

Patrick Boland, MD, assistant professor of oncology, Roswell Park Cancer Institute, Buffalo, NY, who specializes in the treatment of gastrointestinal cancers and primarily colorectal and anal cancers, told Healio.com the results are “fairly early on, but very exciting.”

These clinicians offer key takeaways along with insight on what the research means for managing patients every day.

PD-1 blockade benefits patients with mismatch repair deficiency

Presented in a clinical science symposium on immunotherapy, a study in patients with and without DNA mismatch repair (MMR)-deficiency — with resulting microsatellite instability (MSI) — suggests a potential for pembrolizumab, Bekaii-Saab said.

Dung T. Le, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Md., and colleagues compared the effects the single agent anti-PD-1 pembrolizumab on various cancers, with a focus on colorectal cancer.

“It was very interesting to see that those patients who were MMR-deficient had close to a 40% immune-related response rate from the PD-1 inhibitor,” Bekaii-Saab said.

The study met its co-primary endpoints of immune-related objective response rate and immune-related progression-free survival at 20 weeks.

The activity observed in the MSI-high tumors was “really spectacular,” according to Boland. “All told, 90% of patients [had] clinical benefits — either response or stable disease.”

Although the data represents only about 3% of patients with metastatic cancer, Boland noted this frequency is on par with low-frequency alterations detected in lung cancer, for which multiple drugs are already approved and several are being further developed.

Boland said the results are preliminary but promising, and he anticipates the therapy becoming available to treat patients in the future; additional studies are already being planned.

“Everybody is really excited about this,” Boland said. “For me, if I had a patient who I knew was MSI-high colorectal cancer, I would be looking for a way to get them on a study that involves use of a PD-1 inhibitor, or a like trial, because immunotherapy may work in these tumor types.”

Bekaii-Saab urged caution before initiating PD-1 treatment in every patient with MSI colorectal cancer, noting the study was not randomized and comprised no control arm. But he called the findings “exciting enough" to move forward to a phase 2 randomized or even consider a phase 3 study.

“At this point in time, I would consider it in the box of interesting, but not changing our standard-of-care yet,” he said. “I’m looking forward to more data in the randomized setting and seeing how [PD-1 inhibitors] perform vs. chemotherapy in other settings.”

Anti–PD-1 antibody and advanced gastric cancer

An investigation assessing the safety and efficacy of pembrolizumab in patients with advanced gastric cancer by Yung-Jue Bang, MD, of Seoul National University College of Medicine, South Korea, and colleagues helped further clarify which patients may benefit from immunotherapy, Alberts said.

The data, presented in the oral abstract session on GI noncolorectal cancer, revealed the anti–PD-1 monoclonal antibody offered manageable toxicity and promising anti-tumor activity in patients, from Asia-Pacific and around the world, with recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction.

With an overall response rate of 33% based on investigator review that was associated with PD-L1 expression level, and 6-month PFS and OS rates of 24% and 69%, respectively, the results were encouraging.

“The data was not necessarily earth-shaking, but it helps guide the future development of clinical trials and ultimately patient care,” Alberts said.

With immunotherapy an increasingly important area in cancer treatment, he noted improving the characterization of the molecular profiles of tumors and how they influence outcomes, has become key in managing patients with colorectal cancer.

Identifying patients with tumors more sensitive to immunotherapy “would allow the opportunity to pull out subsets of patients who eligible right now — at least for clinical trials,” Alberts said.

HCC and PD-1 inhibitors

Despite being limited in size and also without randomization, research by Anthony B. El-Khoueiry, MD, of the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, Calif., and colleagues into the effect of the PD-1 inhibitor nivolumab in hepatocellular carcinoma showed a “very interesting” response rate, according to Bekaii-Saab.

“The response was 23% in a group of patients afflicted with a disease where we see a very low response rate; it’s exciting from that standpoint,” he said.

The duration of complete response, as presented in the immunotherapy clinical science symposium, was between 14 and 17 months. Partial response was between 1 and 8 months and stable disease was between 1.5 and 17 months, with a 6-month OS rate of 72%.

“[The findings] move the field forward in treating a disease that is incredibly desperate and doesn’t have many standards,” Bekaii-Saab said.

However, further investigation is required before clinicians treating liver cancer can consider the therapy as a potential change to usual care — just as for those treating colorectal and other cancers.

“We have to wait for more mature data from larger randomized trials,” he said.

HERACLES and HER2 expression

Research by Salvatore Siena, MD, of the Niguarda Cancer Center, Milan, Italy, and colleagues presented in the GI colorectal cancer oral session shows evidence of benefit for trastuzumab and lapatinib together for colon cancer, Alberts said.

In the HERACLES trial — assessing 8-week objective response with the drug combination in patients with HER2-amplified, KRAS exon 2 wild type, metastatic colorectal cancer who were resistant to standard therapies — the dual therapy met its primary endpoint.

“There’s now a recognition that there may be 5% or 6% of patients who have tumors that overexpress HER2,” Alberts said. “That’s always been important in breast cancer and stomach cancer, and now we’re recognizing there’s a subgroup in colon cancer.”

The findings increase awareness for practitioners and could present an opportunity to help patients who may not have alternative treatment options, he noted.

“Particularly in refractory colon cancer, there’s a subset of patients [in whom] it’s important to look for overexpression of HER2,” Alberts said. “That’s one of the things buried in everything else that might get overlooked — so it’s potentially interesting and exciting.”

With RAS, BRAF and MMR the main focus areas in managing colon cancer, these data broaden the thinking to other prognostic factors, Alberts said.

UK Medical Research Council

Results from a phase 3 trial presented in the gastrointestinal noncolorectal cancer session demonstrated that a combination of two chemotherapies offered patients with esophageal cancer, potentially amenable to surgical treatment, similar benefits as three, with less risk.

Derek Alderson, MD, of the Queen Elizabeth Hospital, Birmingham, U.K., and colleagues investigated whether more chemotherapy — four cycles of epirubicin, cisplatin and capecitabine (ECX) — would improve outcomes over two cycles of cisplatin and fluorouracil.

The standard-of-care in the United Kingdom for locally advanced esophageal cancer, two cycles of cisplatin and fluorouracil, followed by surgery, had previously been set in a trial performed by this group.

The three-drug regimen led to higher overall toxicity without improving OS, although the treatment did result in some benefit in PFS, DFS and tumor regression at resection.

“You don’t really need the third drug, epirubicin, which can create a lot of toxicities for patients,” Alberts said. “For many years, particularly for stomach cancer and to some degree esophageal cancer, we’ve used a three-drug combination, so that was helpful to understand.”

References:

Alderson D, et al. Abstract 4002.

Bang YJ, et al. Abstract 4001.

El-Khoueiry AB, et al. Abstract LBA101.

Le DT, et al. Abstract LBA100.

Siena S, et al. Abstract 3508.

All presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosures : Alberts and Boland report no relevant financial disclosures. Bekaii-Saab reports serving as a consultant for Bristol-Myers Squibb.