2022 ASCO Meeting Agenda Sets the Stage for the Future of Care

The 2022 American Society of Clinical Oncology (ASCO) Annual Meeting returns to Chicago, Illinois, with an agenda highlighting primary outcomes as well as extended follow-up data across malignancies.

“We’ve made tremendous strides in [research over] the past few years and I’m looking forward to hearing what my colleagues have to say about their work and progress in the years to come,” Eric Jonasch, MD, said in an interview with OncLive^® ahead of the conference.

Late-breaking abstracts in breast, lung, prostate, and hematologic malignancies highlight advances in the application of novel and established agents in pivotal phase 3 trials. In a series of interviews with OncLive® investigators across specialties discuss the most anticipated abstracts from the upcoming meeting and highlight the data they will present for their respective fields.

BREAST CANCER

Paolo Tarantino, MD, clinical research fellow at Dana-Farber Cancer Institute in Boston, Massachusetts

Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study (Abstract LBA3)

The primary end point of the pivotal phase 3 DESTINY-Breast04 (NCT were met after fam-trastuzumab deruxtecan-nxki (Enhertu) according to a news release ahead of the 2022 ASCO meeting.¹ Patients treated with the antibody-drug conjugate achieved statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer regardless of hormone receptor (HR) status vs physician’s choice of chemotherapy.

“DESTINY-Breast04 was the first phase 3 trial launched to confirm the paradigm of HER2-low [disease] and it was a trial which included patients with pretreated HER2-low tumors both with hormone receptor–positive and triple-negative disease…not only PFS, which was the primary end point, but also OS was improved with trastuzumab deruxtecan therapy and these might change the way we treat these patients who are pretreated with chemotherapy with or without endocrine therapy.”

Primary results from TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer (Abstract LBA1001)

In March 2022, Gilead, the developer of sacituzumab govitecan (Trodelvy) announced that the phase 3 TROPiCS-02 trial met its primary end point of demonstrated PFS improvement among patients with hormone receptor–positive/HER2-negative advanced breast cancer vs chemotherapy.² The data potentially add an additional agent to the treatment landscape for this patient population.

“Other big news we had recently was the that TROPiCS-02 trial [data] were positive meaning that sacituzumab govitecan, an anti-TROP2 antibody-drug conjugate, after being approved in triple-negative disease is also more active than chemotherapy in the hormone receptor–positive disease. Potentially, in this pretreated population we might have different ADCs available, and we might need to decide which ones to prioritize.”

GENITOURINARY CANCERS

Eric Jonasch, MD, professor in the Department of Genitourinary Medical Oncology, The University of Texas MD Anderson

Long-term follow-up data from 2 trials of belzutifan (Welireg) in patients with renal cell carcinoma (RCC) will contextualize the clinical benefit of the agent across variant histologies.

Phase 1 LITESPARK-001 (MK-6482-001) study of belzutifan in advanced solid tumors: Update of the clear cell renal cell carcinoma (ccRCC) cohort with more than 3 years of total follow-up (Abstract 4509)

Among heavily pretreated patients with clear cell RCC (n = 55), previously reported data from the phase 1/2 LITESPARK-001 trial (NCT02974738) showed that the small molecule inhibitor of HIF-2α elicited an objective response rate of 25%. The median progression-free survival was 14.5 months.³ Investigators will present data with more than 3 years of follow-up during the meeting.

“The journey of discovery that has led to the development of [belzutifan] is quite amazing from the discovery of the [Von Hippel-Lindau] VHL gene at the [National Institutes of Health] in 1993 to the work of [Peter J. Ratcliffe, FRS, FMedSci]; [William G. Kaelin, Jr, MD]; and [Gregg L. Semenza, MD, PhD,] being awarded the Nobel Prize in 2019, to understanding how VHL regulates the HIF and other factors to the development of this drug by the group at UT Southwestern…This is an amazing example of science that is properly motivated that led to highly effective therapy for this disease.”

LITESPARK-004 (MK-6482-004) phase 2 study of belzutifan, an oral hypoxia-inducible factor 2α inhibitor (HIF-2α), for von Hippel-Lindau (VHL) disease: Update with more than two years of follow-up data (Abstract 4546)

Data from the phase 2 LITESPARK-004 trial (NCT03401788) supported the approval of belzutifan patients with von Hippel-Lindau (VHL) disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors not requiring immediate surgery in 2021. At 18-month follow-up the agent elicited an overall response rate of 49% (95% CI, 36%-62%) among patients with VHL-associated RCC.⁴

“I am also presenting the follow-up data on LITESPARK-004. I am extremely excited about [the data for] belzutifan in patients with VHL disease [in which] we demonstrate the [benefit of] this agent in a hereditary patient population continues to improve. “It’s very exciting for patients with VHL disease seeing that this agent is finally providing an effective treatment option for this devastating hereditary disorder.”

Adjuvant pembrolizumab for postnephrectomy renal cell carcinoma (RCC): Expanded efficacy analyses from KEYNOTE-564 (Abstract 4512)

In November 2021, the FDA approved pembrolizumab (Keytruda) for the adjuvant treatment of patients with RCC at intermediate/high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions based on data from KEYNOTE-564 (NCT03142334).5 Data showed that pembrolizumab significantly improved disease-free survival (DFS) vs placebo with 24-month DFS rate of 77.3% vs 68.1%, respectively (HR, 0.68; 95% CI, 0.53-0.87; P = .002). Lead investigator Toni K. Choueiri, MD, the 2021 Giants of Cancer Care^® award winner in genitourinary cancers will presented efficacy analysis at the meeting.

HEMATOLOGIC MALIGNANCIES

Michael Wang, MD, professor in the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center in Houston

Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrutinib in combination with bendamustine-rituximab (BR) and R maintenance as a first-line treatment for older patients with mantle cell lymphoma (MCL) (Abstract LBA7502)

Data for the phase 3 SHINE trial (NCT01776840) will be presented with approximately 7 years follow-up. The study enrolled over 500 elderly patients (age ≥ 65 years) with newly diagnosed mantle cell lymphoma (MCL) who were not candidates for autologous stem cell transplant to receive ibrutinib (Imbruvica) in combination with bendamustine (Bendeka) and rituximab (Rituxan).⁶

“This is a study in the first-line study treatment for elderly patients with MCL, older patients with MCL often cannot tolerate intensive therapy with very poor outcomes. Bendamustine/rituximab is most commonly used therapy and literature has [shown] that rituximab was useful after bendamustine/rituximab in this clinical trial we added ibrutinib. This trial was successful because the primary end point.”

Three-year follow-up of outcomes with KTE-X19 in patients with relapsed/refractory mantle cell lymphoma in ZUMA-2 (Abstract 7518)

The phase 2 ZUMA-2 trial (NCT02601313) evaluated the efficacy of the CD19-direct CAR T cell therapy brexucabtagene autoleucel (Tecartus) in heavily pretreated patients with relapsed/refractory MCL. Prior results with 1-year follow-up (median follow-up 17.5 months) showed that among 60 patients who received the cellular therapy, the objective response rate was 92% (95% CI, 82%-97%), with complete remission rate of 67% and a partial remission rate of 25% (n = 15).⁷

“This 3-year follow-up study showed that the single infusion of brexucabtagene autoleucel in elicited high durable response in relapsed MCL.”

LUNG CANCER

Mary E. O’Brien, MD, medical director of Columbia University Emergency Medical Services in New York, New York

EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study of pembrolizumab versus placebo for completely resected early-stage non-small cell lung cancer (NSCLC): Outcomes in subgroups related to surgery, disease burden, and adjuvant chemotherapy use (Abstract 8512)

A subgroup analysis of the phase 3 KEYNOTE-091/PEARLS trial (NCT02504372) will highlight outcomes observed in key subgroup analyses of patients with resected early-stage non–small cell lung cancer (NSCLC). Data presented during a 2022 European Society for Medical Oncology Plenary Session showed that disease-free survival (DFS) was significantly improved with pembrolizumab in the intention-to-treat population (HR, 0.76; 95% CI 0.63-0.91; P = .0014).⁸

“[With this treatment] we are probably going to add another 10% to cure rate for lung cancer. It took us about 20 years to get 5% from chemotherapy [and] 5% of lung cancers are still thousands and thousands of patients, anything over 5% is very significant to the [number] of lives we are saving. With this I think we are going to get to 10%; it will take a few more years to conform this but we are very sure that this treatment is decreasing the chance of the disease coming back.”

First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients (pts) with metastatic non–small cell lung cancer (NSCLC): 3-year update from CheckMate 9LA (Abstract LBA9026)

Data from the CheckMate 9LA (NCT03215706) will include an additional 2 years of follow-up. At a median follow-up of 13.2 months, the median OS was 15.6 months (95% CI, 13.9-20.0) in patients who received nivolumab (Opdivo) plus ipilimumab (Yervoy) with 2 cycles of chemotherapy vs 10.9 months (95% CI, 9.5-12.6) in the control group who received 4 cycles of chemotherapy (HR, 0.66; 95% CI, 0.55-0.80).⁹

GASTROINTESTINAL CANCERS

Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC): results from the phase 3 PARADIGM trial (Abstract LBA1)

The phase 3 PARADIGM trial (NCT02394834) biomarkers which may be predictors of efficacy and safety of treatment with modified regimen of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX) plus bevacizumab (Avastin) or panitumumab therapy in patients with chemotherapy-naïve unresectable advanced or recurrent colorectal cancer whose tumors are RAS (KRAS/NRAS) wild-type.

Five-year survival outcomes with nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for metastatic non–small cell lung cancer (NSCLC): Results from CheckMate 227 (Abstract LBA9025)

Investigators will present 5-year landmark analysis of the phase 3 CheckMate 227 (NCT02477826) trial of ipilimumab (Yervoy) and nivolumab (Opdivo) in the first-line treatment of patients with metastatic NSCLC. Data are anticipated to confirm the durability of the immunotherapy combination for this patient population, which was approved in May 2020 for patients whose tumors express PD-L1 (≥ 1%), as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.¹⁰

MELANOMA

Nivolumab (NIVO) + relatlimab (RELA) versus NIVO in previously untreated metastatic or unresectable melanoma: OS and ORR by key subgroups from RELATIVITY-047 (Abstract 9505)

Data from the phase 2/3 RELATIVITY-047 trial (NCT03470922), presented during the March 2022 ASCO plenary session, showed that the fixed-dose combination of relatlimab and nivolumab (Opdivo) demonstrated a PFS and OS benefit, as well as a higher objective response rate vs nivolumab alone in previously untreated patients with metastatic or unresectable melanoma. Data from key subgroups will be presented at the meeting.¹¹

References

1. Enhertu significantly improved both progression-free and overall survival in DESTINY-Breast04 trial in patients with HER2-low metastatic breast cancer. News release. AstraZeneca. February 21, 2022. Accessed May 24, 2022. bit.ly/38nPCzu
2. Phase 3 TROPiCS-02 study met the primary endpoint of progression-free survival in late-line HR+/HER2- metastatic breast cancer. News release. Gilead Sciences, Inc. March 7, 2022. Accessed May 25, 2022. bit.ly/3GhuO9k
3. Choueiri TK, Bauer TM, Papadopoulos KP, et al. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021;27(5):802-805. doi:10.1038/s41591-021-01324-7
4. FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. FDA. Updated February 1, 2022. Accessed May 25, 2022. bit.ly/3m1vOFn
5. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. FDA. November 17, 2021. Accessed May 25, 2022. bit.ly/3NFDEQJ
6. Janssen seeks approval of a new indication for Imbruvica (ibrutinib) for use in patients with untreated mantle cell lymphoma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. March 8, 2022. Accessed May 25, 2022. bit.ly/3r2wHQM
7. Wang ML, Munoz J, Goy A, et al. One-year follow-up of ZUMA-2, the multicenter, registrational study of KTE-X19 in patients with relapsed/refractory mantle cell lymphoma. Presented at: 2021 EBMT Annual Meeting; March 14-17, 2021; virtual. Accessed May 25, 2022. bit.ly/3z6ZHvk
8. Paz-Ares L, O’Brien MER, Mauer M, et al. Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study. Ann Oncol. 2022;33(4):P451-453. doi:10.1016/j.annonc.2022.02.224
9. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):P198-211. doi:10.1016/S1470-2045(20)30641-0
10. FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥1%). FDA. May 15, 2020. Accessed May 25, 2022. bit.ly/3LOODFS
11. Long GV, Hodi FS, Lipson EJ, et al. Relatlimab and nivolumab vs nivolumab in previously untreated metastatic or unresectable melanoma: overall survival and response rates from RELATIVITY-047 (CA224-047). J Clin Oncol. 2022;40(suppl 36):360385. doi:10.1200/JCO.2022.40.36_suppl.360385