During the virtual 2021 ASCO Annual Meeting, important results from many clinical trials in both solid tumors and hematologic malignancies will be reported. Below, oncology experts have highlighted their most anticipated abstracts, which we will cover online as a part of CCO’s Independent Conference Coverage of ASCO 2021. As the ASCO virtual annual meeting unfolds, remember to check the CCO website often for downloadable slidesets summarizing the data from these studies and more and then again after the meeting for CME-certified online activities, featuring expert analyses and perspectives on the clinical implications of the new data.

Top Picks: Hematologic Malignancies
Several interesting and potentially practice-changing studies in hematologic malignancies are being reported at ASCO 2021.

Ian W. Flinn, MD, PhD: Several interesting abstracts in lymphoma will be presented at ASCO. In a randomized, head-to-head trial by Byrd and colleagues, the BTK inhibitor acalabrutinib is shown to be equivalent in efficacy but with fewer adverse events than ibrutinib in patients with previously treated chronic lymphocytic leukemia (CLL), definitively demonstrating potentially practice-changing results that had previously been suspected in single-arm studies. In the CAPTIVATE study, Ghia and colleagues present data from an all-oral CLL regimen combining venetoclax with ibrutinib. Nearly all patients responded, and three quarters of patients achieved undetectable measurable residual disease, allowing some patients to stop this therapy after a year of the combination, potentially avoiding IV medications and long-term complications of continuous therapy. In a diffuse large B-cell lymphoma study, Clausen and colleagues present results of treatment with epcoritamab, a CD20 x CD3 bispecific antibody, with a complete remission rate closer to what is seen with CAR T-cells but with an improved safety profile. More patients will need to be studied, but these are promising results for a potential off-the-shelf alternative to CAR T-cell therapy in this patient population.

Eunice S. Wang, MD: Perhaps one of the most interesting leukemia studies being discussed at this ASCO is in chronic myeloid leukemia (CML). Cortes and colleagues provide their primary analysis of the phase II OPTIC trial, showing best approaches to reducing toxicity from the tyrosine kinase inhibitor ponatinib in relapsed/refractory chronic-phase CML with dose optimization. In acute lymphoblastic leukemia (ALL), Shah and colleagues report phase II results of the ZUMA-3 study of the anti-CD19 CAR T-cell therapy KTE-X19 in adult patients with relapsed/refractory B-cell ALL. At a median16.4 months of follow-up, overall survival (OS) was not yet reached in responding patients in this heavily pretreated population. Pullarkat and colleagues report on venetoclax plus azacitidine in untreated patients with myelodysplastic syndromes, which suggest better outcomes than azacitidine alone.  

Shaji K. Kumar, MD: In multiple myeloma (MM), new and updated data from several trials in both the frontline and relapsed/refractory settings will be presented. For frontline treatment approaches, we will see longer-term follow-up from the FORTE trial, which assessed carfilzomib-based induction and consolidation, with 4-year progression-free survival data by patients’ cytogenetic risk. We will also see updates from CASSIOPEIA part 2 exploring the efficacy of daratumumab-based maintenance vs observation after induction/consolidation with D-VTd vs VTd.

For relapsed/refractory MM, a major topic again this year is use of anti-BCMA–targeted therapy. One interesting concept is the subcutaneous dosing of anti-BCMA bispecific antibodies, such as the data from the phase I MagnetisMM-1 trial with elranatamab. We will also see updates from studies on the FDA-approved agents belantamab mafodotin and idecabtagene vicleucel.

Patients who are lenalidomide refractory and proteasome inhibitor exposed are often older and become less tolerant of aggressive therapy with multiple lines of treatment. This continues to be a difficult patient population to treat, and an interesting phase II trial being presented this year will report data comparing the all-oral regimens ixazomib/dexamethasone vs pomalidomide/dexamethasone in this patient population. Updates of the ICARIA-MM trial with isatuximab/pomalidomide/dexamethasone and the IKEMA trial with isatuximab/carfilzomib/dexamethasone will be presented, including a subgroup analysis of IKEMA in older patients.

Top Picks: Lung Cancer

Karen L. Reckamp, MD, MS, and Zofia Piotrowska, MD, MHS have identified several key studies in lung cancer of interest at ASCO 2021.

The first adjuvant immunotherapy (IO) study in resected non-small-cell lung cancer (NSCLC) will be presented: Primary results from the global phase III IMpower010 trial met its primary endpoint, demonstrating improved disease-free survival with adjuvant atezolizumab vs best supportive care among patients with PD-L1–positive disease after adjuvant chemotherapy in resected stage IB-IIIA NSCLC. These data promise to redefine adjuvant treatment for early-stage NSCLC. In advanced NSCLC, data informing how best to treat patients with PD-L1 tumor proportion scores of 1% to 49%, an important clinical question that oncologists struggle with, will be presented. In an exploratory analysis by the FDA, pooled data from 8 randomized clinical trials demonstrated improved progression-free survival and OS with combination chemotherapy/IO vs IO alone among most patient subgroups when PD-L1 was not highly expressed. The exception was patients 75 years of age or older, where similar outcomes were seen, and IO alone may be a reasonable option. These data are hypothesis generating but demonstrate the continued role of chemotherapy when IO is used in improving outcomes for patients with advanced NSCLC.

In the realm of targeted therapy, an update of a phase I study will be presented showing promising antitumor activity of the novel HER3-targeted antibody–drug conjugate patritumab deruxtecan across a variety of resistance mechanisms to EGFR tyrosine kinase inhibitor therapy among patients with heavily pretreated EGFR-mutant NSCLC. Finally, highlighting this year’s theme of equity, a highly relevant retrospective observational study evaluating racial disparities in biomarker testing and clinical trial enrollment of patients with advanced/metastatic NSCLC promises to shed light on barriers and opportunities to balance care across all patients with this disease.

Top Picks: Breast Cancer

Joyce O’Shaughnessy, MD: In the Plenary Session, we will see the primary analysis of the phase III OlympiA trial comparing adjuvant olaparib vs placebo in patients with high-risk, germline BRCA–mutated, HER2-negative early breast cancer following definitive local treatment and (neo)adjuvant chemotherapy. Outcomes of this study promise to be telling, as the independent data monitoring committee recommended an early primary analysis due to a positive interim signal for the primary endpoint of invasive disease–free survival (IDFS). Next, Martin and colleagues will report an important subgroup analysis of the phase III monarchE trial, indicating that the addition of abemaciclib to adjuvant endocrine therapy significantly improves IDFS and distant relapse–free survival in patients with hormone receptor–positive, HER2-negative early breast cancer at very high risk of recurrence following neoadjuvant chemotherapy. Finally, Loibl and colleagues will present positive long-term outcomes—including improved OS—observed when patients with triple-negative breast cancer were treated with neoadjuvant durvalumab plus chemotherapy in the phase II GeparNUEVO trial.

Top Picks: Gynecologic Cancer

Angeles Alvarez Secord, MD: In the Plenary Session, Mileshkin and colleagues will present data from the phase III OUTBACK trial evaluating whether the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves survival for women with locally advanced cervical cancer (FIGO stage IB₁ and node positive, IB₂, II, IIIB, or IVA). If positive, results from this study have the potential to change the standard of care (SoC) in this setting. In ovarian cancer, Laszlo and colleagues will report positive data from the randomized phase III trial of pafolacianine sodium injection (OTL38) intraoperative near-infrared fluorescence (NIRF) imaging to detect additional lesions not detected by palpation and normal white light in 150 patients with ovarian cancer undergoing surgery. The abstract indicates that OTL38, along with NIRF, identifies a significant number of additional lesions compared with normal white light and palpation. Also in ovarian cancer, Westin and colleagues will report positive results from the phase III EFFORT trial evaluating adavosertib with or without olaparib in 80 women with ovarian cancer and documented progression on PARP inhibitors with highly encouraging antitumor activity for adavosertib alone and in combination with olaparib compared with historical studies of cytotoxic therapy. Finally, Zola and colleagues will report data from the TOTEM study of intensive vs minimalistic follow-up in 1884 patients with endometrial cancer showing a weak and uncertain advantage in detecting earlier asymptomatic relapses but no improvements in survival.

Top Picks: Skin Cancer

Michael A. Davies, MD, PhD, and Evan J. Lipson, MD: The melanoma oral session at ASCO 2021 includes several interesting and impactful studies for patients with melanoma. The phase III RELATIVITY-047 trial comparing nivolumab with and without relatlimab, an anti–LAG-3 antibody, in treatment-naive patients with stage IV melanoma will be presented by Lipson and colleagues. The trial met its primary endpoint of improved progression-free survival with the combination therapy establishing the LAG-3 pathway as the third immune checkpoint pathway, after CTLA-4 and PD-1, for which blockade has clinical benefit.

Patients with advanced melanoma and confirmed progression on a PD-1 or PD-L1 inhibitor comprise a population with limited therapeutic options and encouraging updates from 2 studies addressing this unmet need will be presented. Larkin and colleagues will present the 28-month follow-up data from a phase II multicenter study evaluating the efficacy and safety of lifileucel, an adoptive cell therapy using tumor-infiltrating lymphocytes, in patients with advanced melanoma who have progressed on anti–PD-1 therapy and a BRAF inhibitor with or without an MEK inhibitor, if BRAF^V600 positive. Data presented in the abstract are encouraging for lifileucel as a potential regimen for this patient population with high unmet need. An update on the efficacy and continued durability of the combination of lenvatinib plus pembrolizumab in the phase II LEAP-004 II study will be reported by Arance and colleagues, offering support for further development of this combination as a potential regimen for this patient population with high unmet need.

The oral session also includes updates from 2 key clinical trials. New data for part 2 of the KEYNOTE-054 study in which the efficacy of pembrolizumab was assessed in the patients who recurred (after either placebo or adjuvant pembrolizumab) will be examined by Eggermont and colleagues. Dummer and colleagues will report the 5-year results from the COLUMBUS trial of encorafenib and binimetinib targeted therapy for patients with BRAF-mutant stage IV disease, and these data will be interesting for comparison to the 5-year data previously reported for the other FDA-approved targeted therapies and immunotherapies.

Top Picks: Genitourinary Cancers

Daniel P. Petrylak, MD, and Elizabeth R. Plimack, MD, MS: This year in genitourinary cancers, we have 2 late breaking abstracts being presented in the Plenary Session: the phase III VISION trial with lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) (Abstract LBA4) and the phase III KEYNOTE-564 study with postnephrectomy adjuvant pembrolizumab vs placebo for patients with renal cell carcinoma (RCC) (Abstract LBA5).

In prostate cancer, other interesting abstracts being presented include the first results of the phase III PEACE-1 trial in men with de novo metastatic castration-sensitive prostate cancer. This trial is assessing the SoC—androgen deprivation therapy with or without docetaxel—vs SoC plus abiraterone vs SoC plus radiotherapy vs SoC plus abiraterone plus radiotherapy. An updated safety analysis of the phase III PEACE-III trial, which assessed the combination of Ra-223 with enzalutamide vs enzalutamide alone, will provide data on the importance of the use of bone-protecting agents for patients with mCRPC.  

For RCC, in addition to the plenary presentation mentioned above, updates will be presented from the KEYNOTE-426 trial with first-line pembrolizumab plus axitinib vs sunitinib and the CheckMate 9ER trial with first-line nivolumab plus cabozantinib vs sunitinib for advanced clear-cell RCC.

Finally, in bladder cancer, other interesting abstracts to watch for include updates on the KEYNOTE-052 trial with pembrolizumab as first-line therapy in cisplatin-ineligible patients with advanced bladder cancer and the KEYNOTE-045 trial with pembrolizumab as therapy for recurrent bladder cancer after platinum-based chemotherapy.

Top Picks: Gastrointestinal Cancers

Manish A. Shah, MD: Clinical data from several key trials of immune checkpoint inhibitor therapy for advanced gastroesophageal and colorectal cancers will be presented at ASCO 2021. The first data from CheckMate 648, a phase III study of first-line nivolumab plus ipilimumab vs nivolumab plus chemotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC), will be presented as a late-breaking abstract (Abstract LBA4001). Based on the results of CheckMate 649 (for which we will see updated efficacy and safety data at ASCO 2021), nivolumab plus chemotherapy was approved for patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma. CheckMate 648 has the potential to establish a chemotherapy-free SoC for patients with advanced ESCC.

Interim results from KEYNOTE-811 will also be presented. This is a phase III study, the results from which led to the accelerated approval of pembrolizumab plus trastuzumab plus chemotherapy as first-line therapy for patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ cancer. Per the prescribing information, treatment with the pembrolizumab combination was associated with an overall response rate (ORR) of 74%, compared with an ORR of 52% observed with trastuzumab plus chemotherapy alone.

We will also see the highly anticipated final OS data from KEYNOTE-177, a phase III study that compared first-line pembrolizumab with chemotherapy for patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer and established a SoC in this setting.

Additional Studies to Watch
The CCO Conference Coverage of ASCO 2021 will also include slidesets of other important studies including:

• Update on the VIALE-A trial of venetoclax and azacitidine in AML  
• Results from a phase II study of enasidenib with and without azacitidine for higher-risk IDH2-mutant myelodysplastic syndromes
• A multivariate analysis for prognostic factors for OS and relapse-free survival from the QUAZAR AML-001 trial of oral azacitidine
• Primary analysis of the phase II trial of tisagenlecleucel in relapsed/refractory follicular lymphoma  
• Interim results on the safety and efficacy of the combination of venetoclax, lenalidomide, and rituximab in newly diagnosed mantle cell lymphoma  
• 2 updates on first-line combination immunotherapy for advanced NSCLC: a 4-year update of CheckMate 227 evaluating nivolumab/ipilimumab vs chemotherapy and a 2-year update of CheckMate 9LA evaluating nivolumab/ipilimumab plus chemotherapy vs chemotherapy alone
• Exploratory subgroup analysis from the phase II CodeBreak 100 trial evaluating sotorasib in pretreated KRAS G12C–mutated NSCLC
• 2 updates on immunotherapy for unresectable stage III NSCLC: 5-year survival update of PACIFIC evaluating durvalumab after chemoradiotherapy and results for all patients enrolled on the phase II KEYNOTE-799 trial evaluating pembrolizumab plus chemoradiotherapy
• OS update from the phase III MONALESSA-3 study of fulvestrant with or without ribociclib in hormone receptor–positive/HER2-negative breast cancer
• 3 studies presenting new data on sacituzumab govitecan in several patient subsets from the ASCENT study in triple-negative breast cancer: an update on the efficacy of sacituzumab govitecan in patients 65 years of age or older; in patients with previous neoadjuvant/adjuvant chemotherapy; and efficacy vs each individual treatment of physician’s choice
• Combined analysis of niraparib from 3 phase III trials in BRCA-mutant ovarian cancer
• Results of a phase II study of niraparib with and without dostarlimab in endometrial carcinoma
• Updated data from CheckMate 577, a phase III study of adjuvant nivolumab following neoadjuvant chemoradiotherapy and surgical resection for patients with stage II/III esophageal/GEJ cancer that led to the approval of nivolumab in this setting
• Updated results including 3-year efficacy outcomes of the CheckMate-511 study comparing different dosing regimens of ipilimumab and nivolumab
• CheckMate 067: 6.5-year outcomes in patients with advanced melanoma
• Neoadjuvant and adjuvant nivolumab with anti–LAG-3 antibody relatlimab for patients with resectable clinical stage III melanoma 

Remember to Check the CCO Website Often During and After ASCO!
These are just a few of the interesting and important abstracts selected by our expert faculty from ASCO 2021. Downloadable slideset summaries of these studies and more will be available on our website as the data are released. After the meeting, comprehensive analyses by our expert faculty members will explore the clinical implications of the data in CME-certified text-based modules.