What’s New in Cancer Research?
The 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, Highlights Major Cancer Research Advances
Both Single and Dual Immunotherapy Regimens Offer Improved Overall Survival for Select Patients With Advanced Esophageal Cancer
“Certain patients with advanced esophageal cancer, who currently have few treatment options, now stand to gain from immunotherapy. The dual immunotherapy combination of nivolumab and ipilimumab is the first chemotherapy-free first-line treatment showing benefit for these patients,” said ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD, FACP, FASCO.
Compared to standard of care chemotherapy, both a dual immunotherapy regimen and a single immunotherapy agent added to chemotherapy extends overall survival (OS) for patients with advanced esophageal squamous cell carcinoma (ESCC), particularly those positive for the immune checkpoint protein PD-L1, according to data from a phase III trial.
In the CheckMate 648, nivolumab plus chemotherapy (cisplatin and 5-fluorouracil) and nivolumab plus ipilimumab both significantly improved OS compared with standard chemotherapy. The co-primary endpoint, OS among patients with PD-L1 ≥ 1%, was significantly better for patients who received nivolumab plus chemotherapy and nivolumab plus ipilimumab compared to chemotherapy alone —15.4 and 13.7 months respectively, compared with 9.1 months.
OS was significantly better among all randomized patients with both nivolumab plus chemotherapy and nivolumab plus ipilimumab compared with chemotherapy alone, 13.2, 12.8, and 10.7 months, respectively.
Progression-free survival (PFS) with nivolumab plus chemotherapy was significantly better than with chemotherapy alone in patients with PD-L1 ≥ 1%.
Treatment advances for recurrent or metastatic ESCC or upper GI cancers have been slower than for other cancers. Chemotherapy with cisplatin and 5-fluorouracil is currently the standard of care for initial treatment in patients with advanced ESCC; however, their prognosis remains poor.
Nivolumab is an immunotherapy agent that belongs to a class of therapies known as checkpoint inhibitors that improves immune system response to tumor cells by blocking a protein (PD-L1) on the tumor cell surface. Ipilimumab is also a checkpoint inhibitor; it targets CTLA4, a protein on T-cells, also improving response against cancer cells.
Nivolumab has been shown to improve survival in patients with advanced ESCC that is refractory or intolerant to previous chemotherapy. The combination of nivolumab with ipilimumab has demonstrated significant clinical activity across several tumor types, leading investigators to examine the combination for the treatment of ESCC.
“The clinically meaningful improvements in survival of these two treatment regimens highlight immunotherapy’s impact on cancer care and should bring new therapeutic options to a group of patients that are often diagnosed when disease has already spread,” said lead author Ian Chau, MD, FRCP, a consultant medical oncologist at the Royal Marsden Hospital in Sutton, United Kingdom.
Post-Surgery Immunotherapy Extends Disease-Free Survival for Select Patients With Kidney Cancer
“Despite surgery, recurrence is common in clear-cell renal cell carcinoma, and should it recur, there are limited curative treatment options for patients. Given the success of pembrolizumab in the KEYNOTE-564 trial, this population may soon have a new standard of care,” said ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD, FACP, FASCO.
Immunotherapy after surgery significantly improved disease-free survival (DFS) for patients with the most common type of kidney cancer, clear-cell renal carcinoma (RCC). A phase III international study presented found that pembrolizumab could offer an effective treatment for patients currently with few other options. KEYNOTE-564 is the first phase III study with a checkpoint inhibitor in the adjuvant setting to improve DFS for patients with high risk fully resected RCC.
At the study’s first interim analysis with 24 months median follow-up, the risk of disease recurrence or death was reduced by 32% compared with placebo. The 24-month estimated DFS rate was 77.3% with pembrolizumab, compared to 68.1% with placebo. Overall, DFS benefit was consistent across subgroups.
The estimated preliminary overall survival rate at 24 months was 96.6% with pembrolizumab and 93.5% with placebo.
Grade 3-5 all-cause adverse events (AEs) were more common with pembrolizumab than placebo — 32.4% versus 17.7% with placebo, respectively. No treatment-related deaths occurred in the pembrolizumab arm.
“Pembrolizumab may provide a promising treatment for patients for whom there are few therapy options. KEYNOTE-564’s disease-free survival supports pembrolizumab as a potential new standard of care in the adjuvant setting to delay disease recurrence for patients with fully resected clear cell RCC,” said lead author Tony Choueiri, MD, who heads the Lank Center for Genitourinary Oncology at the Dana Farber Cancer Institute.
Most patients present with local disease, but up to 40% develop metastatic disease following surgery.
Surgical removal of the tumor by partial nephrectomy or the entire kidney by radical nephrectomy is commonly used to treat RCC. However, patients with intermediate- to high-risk advanced disease are at risk for relapse. Currently, there are no standard treatment options post-surgery.
Pembrolizumab, an immunotherapy agent that belongs to a class of therapies known as checkpoint inhibitors, improves immune system response to tumor cells by blocking a protein (PD-1) on the tumor cell surface. Because targeting PD-1 has proven to be effective efficacy and safe for the treatment of metastatic RCC, researchers investigated PD-1 as a novel target to prevent disease recurrence following surgery.
PARP Inhibitor Significantly Improved Disease-Free Survival in Patients With High-Risk Early-Stage HER2-Negative Breast Cancer with BRCA 1/2 Mutations
“OlympiA’s findings highlight the need for genetic testing for BRCA mutations in patients diagnosed with high-risk early-stage breast cancer. These results could have an important impact on treatment decisions for this patient population, possibly including the use of a PARP inhibitor in the adjuvant setting,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO.
The addition of 1 year of the PARP inhibitor olaparib after completion of standard neoadjuvant or adjuvant chemotherapy, surgery and any radiation therapy needed, significantly improved invasive disease-free (IDFS) and distant disease-free survival (DDFS) in patients with BRCA1/2 germline mutations and high-risk early-stage breast cancer that is negative for human epidermal growth factor receptor 2-(HER2), according to new research.
In the OlympiA study, patients who received standard treatment plus placebo had an estimated 3-year IDFS — being alive and free of recurrent invasive breast cancer and new second cancers — of 77.1%. With the additional administration of 1 year of the oral PARP inhibitor olaparib, the estimated 3-year IDFS was improved to 85.9%. The estimated 3-year DDFS was also improved from 80.4% with placebo to 87.5% with olaparib.
While 3-year estimated overall survival (OS) was greater with olaparib, the difference was not statistically significant at the time of this interim analysis at 2.5 years median follow up.
Adverse events (AEs) were consistent with those previously reported with olaparib treatment. Serious adverse events (SAEs) did not occur more frequently with olaparib than with placebo.
“The OlympiA study results, the first reporting the effects of a PARP inhibitor as an “adjuvant therapy” on survival endpoints, suggest a possible addition to the standard of care for patients with germline BRCA1/2 mutation-associated early breast cancer who have levels of recurrence risk requiring neoadjuvant or adjuvant chemotherapy” said lead author Professor Andrew Tutt, MB ChB, PhD, FMedSci who is the Head of the Division of Breast Cancer Research and Director of the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London and the Breast Cancer Now Research Unit at Guy’s Hospital King’s College London.
In the U.S., 5-10% of breast cancers are related to an inherited gene mutation. Patients with newly diagnosed breast cancers associated with these mutations can present with aggressive, high risk disease. Following completion of multi-modality therapy, which includes surgery, radiation, and chemotherapy, recurrence rates can remain high. There is an unmet need to identify additional novel and effective therapies.
Olaparib is an oral targeted therapy — a poly (ADP-ribose) polymerase (PARP) inhibitor — that is already approved for patients with germline BRCA1 or BRCA2 mutations and metastatic breast cancer.
The OlympiA trial is the first phase III study to report the effect of a PARP inhibitor in any adjuvant setting and in this context is focused on patients with germline BRCA1 or BRCA2 mutations and early-stage, high-recurrence risk breast cancer, following completion of standard multi-modality therapy, which includes a combination of chemotherapy drugs.
Additional Chemotherapy Does Not Offer Survival Benefit for Patients With Locally Advanced Cervical Cancer
“This trial provides clear evidence that the addition of chemotherapy after chemoradiation does not extend survival. The results are immediately practice-changing, showing that this approach should not be used to treat locally advanced cervical cancer. We can now spare our patients the side effects and toxicity that comes with additional chemotherapy,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO.
Additional chemotherapy given after standard chemoradiation treatment does not improve survival for women with locally advanced cervical cancer, and is associated with additional side effects, according to results of a phase III international trial. These findings are likely to immediately change practice for early adopters, who had hoped the regimen would reduce distant disease recurrence in patients.
The standard treatment for locally advanced cervical cancer is chemoradiation with cisplatin-based chemotherapy concurrent with radiation. Yet a significant percentage of patients still relapse and die as a result of distant metastatic disease. Because carboplatin and paclitaxel chemotherapy after chemoradiation are active initial treatments for the metastatic and relapsed setting and are successfully used as adjuvant therapy for other cancers, some oncologists routinely treat women with locally advanced cervical cancer with the regimen. However, until now, there has been no evidence from a large phase III study for or against the addition of chemotherapy in this setting.
The phase III OUTBACK trial demonstrated that chemotherapy following chemoradiation did not improve survival over standard chemoradiation alone for patients with locally advanced cervical cancer.
At 5 years, overall survival (OS) was comparable for both groups – 72% versus 71% respectively, for those receiving adjuvant chemotherapy and those receiving standard care. Also, at 5 years disease had not progressed (progression-free survival, PFS) for 63% of patients who received the additional treatment, compared with 61% who did not. Patterns of disease recurrence were similar in the two treatment groups.
Serious adverse events (grade 3-5) were experienced by more patients up to 1 year after randomization – 81% of patients in the adjuvant chemotherapy group compared with 62% in the standard treatment group.
“The study confirms that chemoradiotherapy alone is currently our best possible treatment for women with locally advanced cervical cancer. Not only is there no benefit with adjuvant chemotherapy, but severe side effects are also increased,” said lead author Linda R. Mileshkin, MD, a medical oncologist at Peter McCallum Cancer Centre in Melbourne, Australia.
Targeted Radiotherapy Offers New Treatment Option for Patients Previously Treated for Metastatic Castration-Resistant Prostate Cancer
“This novel targeted radiotherapy could fill a significant need for patients with metastatic castration-resistant prostate cancer that has progressed despite chemotherapy and targeted antiandrogen therapy. The success of this treatment highlights the importance of investigating alternatives to traditional types of cancer therapies,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO.
The investigational therapy 177Lu-PSMA-617 significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) when added to standard of care treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) compared with standard of care alone, according to new research.
Despite recent therapeutic advances, mCRPC remains incurable. Current treatment options include chemotherapy, androgen receptor blockers, and targeted therapies.
Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed in approximately 80% of patients with prostate cancer, including in metastatic disease. With that high expression, PSMA is an attractive therapeutic target, the researchers explain.
Lutetium-labeled PSMA-617 (177Lu PSMA-617) is a radioactive compound that binds to prostate cancer cells expressing PSMA, enabling targeted delivery of radiation to the tumor and surrounding microenvironment.
In the VISION trial the addition of 177Lu-PSMA-617 to standard of care significantly improved radiographic PFS, compared with standard of care alone, with a median of 8.7 months, compared with 3.4 months, respectively. OS was also significantly improved, with the median 15.3 months versus 11.3 months.
“The findings suggest that 177Lu-PSMA-617 warrants consideration as a new standard of care in this patient population, pending regulatory review and approval,” said lead author Michael J. Morris, MD, who is the head of the Prostate Cancer Section at Sloan Kettering Cancer Center in New York.
Visit the American Society of Clinical Oncology’s patient education website – Cancer.Net – for more research highlights from the 2021 Annual Meeting, as well as more information and resources for cancer survivors and their caregivers.