This past January, the 2020 Gastrointestinal Cancers Symposium was held in San Francisco. More than 3,600 individuals attended and more than 900 abstracts and posters were presented. Among the highlights presented at the meeting and reported in the pages of The ASCO Post, several studies in colorectal, hepatocellular, pancreatic, and gastric/gastroesophageal cancers were of particular interest.
In the pages of this supplement to The ASCO Post, we present highlights from some of these presentations, along with expert commentary from key specialists.
General views: Here, Johanna Bendell presents Abstract 637 for J. Randolph Hecht, MD, (who could not attend session). Photo by © ASCO/Todd Buchanan 2020.
Four years after ASCO launched its first clinical trial—TAPUR, or Targeted Agent and Profiling Utilization Registry—findings have now been reported on the potential benefit of using targeted drugs in patients who have advanced colorectal cancer and few, if any, treatment options.1-3
Richard L. Schilsky, MD, FACP, FSCT, FASCO, ASCO’s Chief Medical Officer, noted that “about 2,200 patients have enrolled, and we’ve treated around 1,800 with novel therapies. Since every treatment we are studying represents an off-label use of an already marketed therapy, the data we are seeing support either using, or not using, a particular drug in a specific tumor type.”
Daniel V.T. Catenacci, MD, discusses Abstracts 278 and 279. Photo by © ASCO/Todd Buchanan 2020.
Emily Bergsland, MD, Program Committee Chair speaks during general session. Photo by © ASCO/Todd Buchanan 2020.
Biomarker-driven matches were made for patients with colorectal cancer who have HER2 amplifications (and received trastuzumab plus pertuzumab), BRAF V600E mutations (and received cobimetinib plus vemurafenib), or high tumor mutational burdens (and received pembrolizumab).
In another notable study of colorectal cancer, authors of the phase III BEACON CRC study reported the benefit of combining two or three targeted agents vs the standard of care.4 Scott Kopetz, MD, PhD, of The University of Texas MD Anderson Cancer Center, presented an updated survival analysis that showed a median overall survival of 9.3 months with both the doublet (encorafenib and cetuximab) and triplet (encorafenib, binimetinib, cetuximab).
For patients with BRAF V600E–mutated metastatic disease, encorafenib plus cetuximab, with or without binimetinib, also demonstrated longer maintenance of quality of life,5 based on patient-reported assessments, over the current standard of care,
Dr. Kopetz noted.
Discussant Christopher M. Booth, MD, of Queens University in Ontario, lauded the authors of BEACON CRC for choosing overall survival and quality of life as endpoints in a trial that benefits a “vulnerable patient population with unmet needs.”
A pivotal phase II trial, the IMbrave150 study, showed a survival benefit for atezolizumab/bevacizumab vs sorafenib as a first-line treatment for unresectable advanced or metastatic hepatocellular carcinoma. Peter R. Galle, MD, of the University Medical Center Mainz, and President of the German Association for the Study of the Liver, reported the results, saying that, “in any given cycle, atezolizumab/bevacizumab was favored, with a lower percentage of patients showing deterioration in quality of life.”6
A. Craig Lockhart, MD, of the University of Miami Sylvester Comprehensive Cancer Center, offered his comments as the invited discussant, calling the quality-of-life results not only statistically significant, but clinically meaningful. “This is reassuring that we’re not only seeing improvements in performance—as in overall survival—but the quality-of-life measures seem to follow.”
Dr. Galle stressed the importance of quality of life, particularly in a palliative setting when lifespan is limited. “In hepatocellular carcinoma, it might even be more complex, because this patient is attacked not just by a tumor, but also by poor liver function,” he said.
The POLO trial of olaparib in BRCA1/2-positive metastatic pancreatic cancer showed that health-related quality of life was preserved with this PARP inhibitor maintenance therapy, evidenced by a low symptom burden over time.7 Michael J. Hall, MD, of Fox Chase Cancer Center, Philadelphia, led the analysis, noting that, for these patients, quality of life is often poor because of the high levels of fatigue, abdominal pain, weight loss, and reduced functional status. Moreover, conventional treatments add even more toxicities, which further compromise well-being.
General views: Panel of speakers answer questions during Oral Abstract Session. Photo by © ASCO/Todd Buchanan 2020.
In speaking of the safety analysis, Michele Reni, MD, of IRCCS Ospedale at San Raffaele Scientific Institute in Milan, Italy, pointed out that with olaparib, symptoms such as fatigue/asthenia, nausea, diarrhea, anemia, decreased appetite, and vomiting occurred early. With the exception of fatigue/asthenia and diarrhea, the adverse events did not increase over time. “At 12 months, 76% of patients still on maintenance olaparib were receiving the recommended dose of 300 mg twice daily,” Dr. Reni said.
The predictive factors for early disease progression are currently unknown, according to POLO study first author Teresa Macarulla, MD, of Val d’Hebron University Hospital and Institute of Oncology, Barcelona. “Assessment of early disease progression in the maintenance setting is limited,” she noted.
The survival benefit of pembrolizumab in advanced gastric/gastroesophageal junction cancer with microsatellite instability-high (MSI-H) tumors or combined positive score (CPS) of ≥ 10 was established in a subanalysis of three KEYNOTE trials.8,9 Joseph Chao, MD, of City of Hope, Duarte, California, said “we see that, in the third line, pembrolizumab definitely leads to a long-term survival benefit. But even in the second line, and in newly diagnosed first-line MSI-H patients, median overall survival is also favored with pembrolizumab over chemotherapy.”
Zev A. Wainberg, MD, of the University of California, Los Angeles, noted that the “response rate with chemotherapy is higher in the front line, but in survival analyses, which is the most important endpoint, there is a much better median overall survival in the patients with a CPS of ≥ 10 with pembrolizumab.”
While pembrolizumab can be given to patients with a CPS ≥ 1, Dr. Wainberg said he “feels a lot better” reserving the drug for patients with a CPS ≥ 10.
It has become clear that a CPS ≥ 10 is a better biomarker than a CPS ≥ 1, but whether it is better than MSI-H may be a matter of debate. MSI-H status is observed in 4% to 5% of patients, whereas a CPS ≥ 10 is found in about 20% of patients.
1. Gupta R, Garrett-Mayer E, Halabi S, et al: Pertuzumab plus trastuzumab in patients with colorectal cancer with ERBB2 amplification or overexpression. 2020 Gastrointestinal Cancers Symposium. Abstract 132. Presented January 25, 2020.
2. Klute K, Garrett-Mayer E, Halabi S, et al: Cobimetinib plus vemurafenib in patients with colorectal cancer with BRAF V600E mutations: Results from the TAPUR study. 2020 Gastrointestinal Cancers Symposium. Abstract 122. Presented January 25, 2020.
3. Meiri E, Garrett-Mayer E, Halabi S, et al: Pembrolizumab in patients with colorectal cancer with high tumor mutational burden: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study. 2020 Gastrointestinal Cancers Symposium. Abstract 133. Presented January 25, 2020.
4. Kopetz S, Grothey A, Yaeger R, et al: Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med 381:1632-1643, 2019.
5. Kopetz S, Grothey A, Van Cutsem E, et al: Encorafenib plus cetuximab with or without binimetinib for BRAF V600E-mutant metastatic colorectal cancer. 2020 Gastrointestinal Cancers Symposium. Abstract 8. Presented January 25, 2020.
6. Galle PR, Finn RS, Qin S, et al: Patient-reported outcomes from the phase III IMbrave150 trial of atezolizumab plus bevacizumab vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma. 2020 Gastrointestinal Cancers Symposium. Abstract 476. Presented January 24, 2020.
7. Hall MJ, Golan T, Hammel P, et al: Pancreatic cancer-specific health-related quality of life with maintenance olaparib in patients with metastatic pancreatic cancer and a germline BRCA mutation: Phase III POLO trial. 2020 Gastrointestinal Cancers Symposium. Abstract 648. Presented January 24, 2020.
8. Chao J, Fuchs CS, Shitara K, et al: Pembrolizumab in microsatellite instability-high advanced gastric/gastroesophageal junction cancer by line of therapy. 2020 Gastrointestinal Cancers Symposium. Abstract 430. Presented January 23, 2020.
9. Wainberg ZA, Fuchs CS, Tabernero J, et al: Efficacy of pembrolizumab monotherapy vs chemotherapy for PD-L1–positive (CPS ≥ 10) advanced G/GEJ cancer in the phase II KEYNOTE-059 (cohort 1) and phase III KEYNOTE-061 and KEYNOTE-062 studies. 2020 Gastrointestinal Cancers Symposium. Abstract 427. Presented January 23, 2020.