Cancer Experts Preview Pivotal Trials at ASCO 2021

The ASCO Annual Meeting’s virtual format—due to the global COVID-19 pandemic—may be continuing for the second consecutive year, but the amount of research being showcased across malignancies is anything but shortchanged. The 2021 conference will encompass more than 2450 abstracts across malignancies, a plethora of which experts say have practice-changing potential.

OncLive® heard from leading oncologists in breast cancer, gynecologic malignancies, multiple myeloma, lung cancer, gastrointestinal cancers, and genitourinary cancers who shared their perspectives on the biggest abstracts being presented at the 2021 ASCO Annual Meeting.

BREAST CANCER

Hal J. Burstein, MD, PhD, institute physician and professor of medicine of Harvard Medical School, Dana-Farber Cancer Institute

OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer (Abstract LBA1).

In the double-blind, multicenter, phase 3 OympiA trial, investigators explored the safety and efficacy of olaparib (Lynparza) tablets vs placebo as an adjuvant treatment for patients with BRCA-mutated, high-risk HER2-negative early breast cancer. Patients must have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.

In February 2021, an independent data monitoring committee concluded that the study crossed the superiority boundary for invasive disease-free survival (iDFS), the primary end point, in this patient population.¹ Further details of this late-breaker abstract will be highlighted during the conference.

“OlympiA [is the] adjuvant olaparib trial for BRCA1/2-associated breast cancers. If clinically compelling, then [this] adds a new selective therapy and would lead to near universal genetic testing after breast cancer diagnosis.”

A randomized phase III post-operative trial of platinum-based chemotherapy (P) versus capecitabine (C) in patients (pts) with residual triple-negative breast cancer (TNBC) following neoadjuvant chemotherapy (NAC): ECOG-ACRIN EA1131 (Abstract 605).

In this stage II/III triple-negative breast cancer (TNBC) population with residual disease following neoadjuvant chemotherapy, the 3-year iDFS was lower than expected regardless of treatment with capecitabine or platinum-based chemotherapy. The findings suggest that the study would likely be unable to demonstrate noninferiority of platinum-based therapy with capecitabine.

“Adjuvant carboplatin was not better than capecitabine for residual cancer after neoadjuvant chemotherapy for triple-negative breast cancer. [This shows that] capecitabine is the treatment of choice, and it makes one question the carboplatin role overall.”

De-escalated neoadjuvant pertuzumab + trastuzumab with or without paclitaxel weekly in HR-/HER2+ early breast cancer: ADAPT-HR-/HER2+ biomarker and survival results (Abstract 503).

In prior findings of one arm of the ADAPT trial, which is an umbrella study, 12 weeks of neoadjuvant paclitaxel, pertuzumab (Perjeta), and trastuzumab (Herceptin) in patients with HER2-positive early breast led to a 90.5% pathologic complete response (pCR) rate.² Without the further use of chemotherapy and using pertuzumab and trastuzumab alone, the pCR rate was 34.4%. At the 2021 ASCO Annual Meeting, the investigators are presenting the first data with survival from this arm.

“Neoadjuvant [paclitaxel, trastuzumab, and pertuzumab] for [estrogen receptor (ER)–negative], HER2-positive breast cancer shows a 90% pCR rate; [trastuzumab/pertuzumab] alone shows a 34% pCR. [This shows that] paclitaxel is a really good drug in HER2-positive tumors, [and that the] game is nearly over for novel studies in neoadjuvant ER-negative, HER2-positive breast cancer.”

Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neoadjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC; Abstract 506).

Durvalumab (Imfinzi) combined with standard neoadjuvant chemotherapy in patients with early TNBC initially showed an encouraging pCR rate, especially in those who had received single-agent durvalumab prior to starting chemotherapy.³ The updated findings showed that the PD-L1 inhibitor significantly improved long-term outcomes of these patients.

“Neoadjuvant durvalumab improves pCR in TNBC, and now shows an OS benefit. [This] supports likely an approval for checkpoint inhibitors in stage II/III TNBC.”

Cancer diagnosis and adverse financial events: Evidence from credit reports (Abstract 6504).

In this retrospective, case-control analysis, investigators researched whether patients with cancer are put at an increased risk of new adverse financial events, which was measured via their credit reports. The data came from the Western Washington Surveillance Epidemiology and End Results cancer registry and voter registry records, as cases and controls, respectively, from 2013 to 2018 that were linked to quarterly credit records from TransUnion.

Findings showed that within 2 years of diagnosis, a significantly higher proportion of patients with cancer had AFEs that were relative to the control group, which were found to have long-lasting effects on patients’ financial status based on the events on their credit reports.

“[This highlights the] financial toxicity of a cancer diagnosis. Folks on the margins [are] all vulnerable to economic setbacks after a cancer diagnosis as measured by mortgage delinquencies, credit ratings, and other metrics.”

GASTROINTESTINAL CANCERS

Tanios Bekaii-Saab, MD, FACP; professor of Mayo Clinic College of Medicine and Science; program leader of Gastrointestinal Cancer, Mayo Clinic Cancer Center; consultant of Mayo Clinic AZ , USA; consortium chair, ACCRU

Liposomal irinotecan (nal-IRI) in combination with fluorouracil (5-FU) and leucovorin (LV) for patients with metastatic biliary tract cancer (BTC) after progression on gemcitabine plus cisplatin (GemCis): Multicenter comparative randomized phase 2b study (NIFTY; Abstract 4006).

In this randomized trial, patients with metastatic biliary tract cancer (BTC) receive liposomal irinotecan (nal-IRI) plus 5-fluoroacil (5-FU)/leucovorin (LV) or 5-FU/LV alone every 2 weeks until disease progression or unacceptable toxicity. Results showed that the addition of nal-IRI showed a significant improvement in both progression-free survival (PFS) and overall survival (OS) and may very well be considered standard in the second-line therapy for this patient population after progression on gemcitabine and cisplatin.

“NIFTY is a relatively large, randomized phase 2b study [N = 178] comparing nal-IRI and infusional 5-FU [i5-FU] vs i5-FU. The primary end point of this study was PFS, with OS, [objective response rate (ORR)] and safety as secondary end points. The study reached its primary end point with more than doubling of the [median] PFS with nal-IRI/i5-FU vs i5-FU. There were significant improvements with [median] OS and ORR as well, with an expected toxicity profile.

“Prior data with FOLFOX from ABC-06 did confirm an improvement in all outcomes [with modified FOLFOX] vs [active symptom control]. The relative concern from ABC-06 included the fact that it was not compared to an active control (such as i-FU) and the overlapping risk of neurotoxicity with oxaliplatin following cisplatin. As such, I think the results of NIFTY are meaningful enough to consider the combination as an option for select patients, pending confirmation in a larger randomized controlled trial.”

Neo-AEGIS (Neoadjuvant trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): Preliminary results of phase III RCT of CROSS versus perioperative chemotherapy (Modified MAGIC or FLOT protocol; NCT01726452; Abstract 4004)

This phase 3 study aimed to answer whether neoadjuvant multimodal treatment with carboplatin/paclitaxel plus radiation therapy (RT), known as CROSS, is more effective than perioperative chemotherapy regimens in patients with locally advanced esophageal cancer and esophagogastric junction adenocarcinoma. However, the design was changed to focus on a noninferior outcome vs a superiority one. Data showed that perioperative chemotherapy is not inferior to CROSS in this setting.

“Neo-AEGIS is a randomized trial comparing the CROSS regimen [CRT regimen] to perioperative chemotherapy with modified MAGIC or FLOT [no RT]. The study was initially powered to show a survival benefit from the CROSS regimen, then changed to a noninferiority outcome. Ultimately, the study was closed to accrual at the request of the Data Safety Monitoring Board, given the absence of futility.

“In other words, the 2 strategies appear to produce similar survival outcomes, putting in question the role of radiation therapy in the perioperative setting. The ESOPEC trial [NCT02509286], which is comparing FLOT to CROSS in a similar setting may ‘break the tie' and move us away from radiation therapy in this setting.”

Adjuvant nivolumab (NIVO) in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): Expanded efficacy and safety analyses from CheckMate 577 (Abstract 4003).

CheckMate 577 served as the basis for the May 20, 2021 adjuvant approval of nivolumab (Opdivo) in patients with completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease in those who received neoadjuvant chemotherapy. Here, the data showed a doubling in the median disease-free survival (DFS) vs placebo at 22.4 months and 11.0 months, respectively, leading to a 31% reduction in the risk of disease recurrence or death (HR, 0.69; 95% CI, 0.56-0.86; P < .001).⁴

At the 2021 ASCO Annual Meeting, additional efficacy, safety, and quality-of-life (QoL) findings from CheckMate 577 will be presented. Thus far, results show clinically meaningful efficacy with nivolumab, which was also been found to be safe and maintain QoL.

“[The data with abstract 4004] brings me to the next abstract of interest, CheckMate 577 comparing the effects of nivolumab vs placebo in patients who received neoadjuvant CRT with residual pathologic disease prior inclusion. This study is transformational as it shows doubling of the DFS with nivolumab vs placebo in a recent publication. The updated presentation continues to suggest meaningful benefits from nivolumab in this setting.”

Final overall survival for the phase III KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC; Abstract 3500).

At the 2020 ASCO Virtual Scientific Program, the KEYNOTE-177 data was one of the pivotal trials presented with pembrolizumab (Keytruda) in the frontline setting for patients with unresectable or metastatic microsatellite instability-high(MSI-H) or mismatch repair deficient(dMMR) CRC.⁵ Here, results showed that the PD-1 inhibitor significantly reduced the risk of disease progression or death by 40% (HR, 0.60; 95% CI, 0.45-0.80; P =.0002) versus standard chemotherapy.5 In June of that year, the FDA approved pembrolizumab for use in that setting, based on the KEYNOTE-177 findings.

This year, the final OS data from KEYNOTE-177 will be unveiled, and while some results are not statistically significant, Bekaii-Saab said that it still cements pembrolizumab as the frontline standard of care for this patient population.

“KEYNOTE-177 is a transformational study that assessed the role of pembrolizumab vs chemotherapy plus biologic of choice in MSI-H first-line treatment of mCRC. The study first reported out in 2020 when it met one of its co-primary end points, PFS, which was double that of the control arm. The median OS results are now being reported, showing again a positive outcome with an improvement for pembrolizumab vs chemotherapy/biologic of choice with a [hazard ratio] of 0.74, although not statistically significant. The high response rate and its durability continue to favor pembrolizumab.

“Same is true for the toxicity profile and QOL measures. The updated results continue to confirm that the standard of care for first-line treatment for all patients with MSI-H mCRC should be pembrolizumab. At least 40% of patients with MSI-H mCRC experiencing durable remissions and will be spared the need to be exposed to chemotherapy, its potential toxicities, and the lack of meaningful long-term efficacy. A previous argument made about a certain percent of patients who may be ‘hyperprogressors’—a concept that has no scientific validity—is now disproven by the fact that OS is improved with pembrolizumab [at least not adversely affected by first initiation of pembrolizumab including in non-responders]. These are great and very meaningful results for this small percent of patients (<4% of mCRC).

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01; Abstract 3505).

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) is studied in patients with HER2-expressing, RAS wild-type metastatic CRC and previously showed efficacy in this setting in the primary findings of the DESTINY-CRC01 trial, which was at a median follow-up of 27.1 weeks. In that analysis, T-DXd elicited a 45.3% ORR in patients with HER2-positive metastatic CRC who were refractory to standard treatment; the median duration of response was not yet reached (95% CI, 4.2 months—not evaluable.⁶ At the 2021 ASCO Annual Meeting, longer efficacy and safety data will be presented.

“T-DXd is an antibody-drug conjugate bound by a linker to a topoisomerase I inhibitor. T-DXd has shown interesting activity across a spectrum of HER2-overexpressing malignancies. DESTINY-CRC01 is a phase 2, open-label, multicenter study of T-DXd in patients with HER2-expressing RAS wild-type mCRC, which was first presented in 2020 and showed promising antitumor activity and a manageable safety profile.

“Here, the authors present updated long-term efficacy and safety data. ORR, the primary end point of this study, is 45% and did not appear to be affected by prior treatment with other anti-HER2 therapies. Not surprisingly, patients with immunohistochemistry [IHC]2+/in situ hybridization [ISH]-, IHC1+ did not exhibit any meaningful activity while IHC2+/ISH+ were associated with a very modest response rate.

“This study continues to illustrate the importance of testing for HER2 amplification early in the setting of mCRC. Although this remains a small subgroup of patients (2% to 4%), the implications of finding HER2 amplification in a RAS wild-type patient are [first, mean] no likelihood for a response to EGFR inhibitors and [second,] importantly, eligibility to treatment with HER2-targeted strategies.

“The results from DESTINY-CRC01 confirm the role of T-DXd in HER2-amplified RAS wild-type mCRC. However, where [do we] place this therapy? Given the high risk of toxicities including the potential lethal risk of interstitial lung disease, T-DXd’s preferred placement would be following failure of dual HER2-targeted therapy, such as following tucatinib [Tukysa] and trastuzumab [Herceptin] on the MOUNTAINEER study. Additional reasoning for placing T-DXd in patients with prior exposure to anti-HER2 targeted therapies is supported by the maintained benefit in this setting as shown in DESTINY-CRC01.”

Dr. Bekaii-Saab will chair the virtual symposium, Show Me the Data®: Evidence-Based Strategies to Leverage Immunogenicity in Hepatocellular Carcinoma, which is part of the Oncology Now Series, hosted by Physicians’ Education Resource® (PER. Register now to attend the event from 7:00 to 9:00 PM on June 9, 2021, as well as other activities in the series.

GENITOURINARY CANCERS

Neeraj Agarwal, MD, a professor of medicine and director of the Genitourinary Oncology Program at the Huntsman Cancer Institute

Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer: VISION (Abstract LBA4).

In VISION, which is an international, prospective, randomized, open-label, multicenter, phase 3 study, investigators are assessing the efficacy and safety of 177 lutetium (Lu)-PSMA-617 plus investigator-chosen best standard of care compared with best standard of care in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The late-breaker abstract has garnered significant interest in the community, as a March 2021 press release announced that the trial met both primary end points of OS and radiographic PFS.⁷

“This trial met both primary end points, which were a significant improvement in OS and radiographic PFS in patients with PSMA-positive mCRPC. In this trial, patients who had progressive PSMA-targeted mCRPC, were randomized to treatment with lutetium-177-PSMA-617vs best standard of care alone.”

Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: KEYNOTE 564 (Abstract LBA5).

The late-breaker abstract does not have available data yet, but in April 2021, it was announced that KEYNOTE-564 met its primary endpoint of DFS with pembrolizumab for the potential adjuvant treatment of patients with renal cell carcinoma (RCC) following nephrectomy or following nephrectomy and resection of metastatic lesions.⁸ An independent data monitoring committee conducted an interim analysis of the trial, which showed that single-agent pembrolizumab demonstrated a statistically significant and clinically meaningfully improvement in DFS compared with placebo.

“The ASCO plenary session will include the results from the phase 3 KEYNOTE-564 study, which will evaluate pembrolizumab, which is a PD-1 inhibitor, in the adjuvant setting of patients with renal cell carcinoma following nephrectomy and resection of metastatic lesions. As we know, in these patients, when they have had successful surgical resection of RCC and some of the metastatic disease sites, they have been rendered what we call [no evidence of disease]. These patients are followed by us with regular scans, and more than half of them experience recurrence of disease. Despite knowing the high-risk nature of the disease, currently we do not have any treatment options for these patients. In this context, pembrolizumab treatment showed improved survival outcomes compared with current standard of care, which is follow-up with scans. It demonstrated statistically significance and clinically meaningful improvement in disease-free survival compared with placebo.”

Real-world first-line (1L) treatment patterns in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a U.S. health insurance database (Abstract 5072);

Real-world utilization of advanced therapies and racial disparity among patients with metastatic castration-sensitive prostate cancer (mCSPC): A Medicare database analysis (Abstract 5073);

Real-world treatment patterns among patients diagnosed with metastatic castration-sensitive prostate cancer (mCSPC) in community oncology settings (Abstract 5074).

Each of the 3 studies link a common theme surrounding the real-world utilization of available therapies for patients with prostate cancer. In the first study, the real-world utilization of effective combination therapies as first-line therapy in insured patients in the United States with metastatic castration-sensitive prostate cancer (mCSPC) was assessed.

In the Medicare database analysis, investigators evaluated the real-world utilization of advanced therapies over time and provides data on utilization patterns among racial minorities that are often underrepresented in clinical trials.

Finally, in the real-world, community oncology setting analysis, investigators explored the impact of new evidence on treatment selection for patients with mCSPC.

“Within the last 5 years, we have seen multiple phase 3 trials with mCSPC where the drugs were [initially] used or approved for mCRPC. When these drugs got moved to the up-front setting, they showed a dramatic improvement in OS. These drugs are docetaxel, abiraterone acetate [Zytiga], enzalutamide [Xtandi], and apalutamide [Erleada]. These 4 drugs are now approved in the mCSPC setting, and the first one to be endorsed by all the guidelines was docetaxel in 2015. In the span of 2, 3, 4 years, all [of these] oral pills got approval.

“These improvements in OS with these drugs are not trivial, not in months, but in 1 to 2 years. I would assume that when we see this magnitude of OS benefit, our patients in the real world are being treated with these medications. The practice-changing trials were presented at ASCO and were published in the New England Journal of Medicine. So, you would assume that these trials are going to and have changed the practice in the real-world population.

“[In abstracts 5072 and 5073,] there was an unacceptably low utilization of these life-prolonging agents in patients with mCSPC in the United States. We like to believe that we spend so much money per capita per patient. We have one of the biggest health systems; it is the most well-resourced health system on the planet. In this health system and in this patient population, what we saw was really astounding. If you look at abstract 5003, you’re looking at more than 35,000 patients. Still, in 2018, less than one-third of patients with mCSPC receive either docetaxel or abiraterone. This is unacceptable because these therapies, which are associated with dramatic improvements in OS, are not being offered to patients.

“[In abstract 5072], which looked at more than 4000 patients and was a different data set, were recruited from the Optum database, which include patient claim data from both commercially insured and Medicare Advantage populations. We are talking about patients well covered by insurance; one can argue in a larger dataset that many of these patients probably were not insured and probably couldn’t afford these drugs. [Still, we] are looking at less than one-third of patients who are being treated with these drugs. [This] brings up the question of ‘Why does this happen?’

“Significant education and awareness are needed and we need to solve this problem. [This shows an] unacceptable low use of life-prolonging therapy. All of these 3 studies point to a huge discordance between real-world practice and phase 3 trial results.”

Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis (Abstract 5002).

In the updated safety analysis of PEACE III, investigators confirmed early fracture rates observed when patients with mCRPC are treated with the addition of radium-223 dichloride (Xofigo) to enzalutamide in the absence of bone-protecting agents.

“This is testing the combination of radium-223 plus enzalutamide vs enzalutamide alone in mCRPC. A previous trial with abiraterone with radium-223, which showed an excessive incidence of fracture in the combination of abiraterone with radium-223, led to this trial doing an amendment mandating the use of bone-protecting agents.

“What we saw was really remarkable. In the absence of bone-strengthening agents—for those who already enrolled on the trial [before the mandate]—there was an increase in the risk of fracture when radium-223 was added to enzalutamide. Very strikingly, the risk was abolished by the use of bone-protecting agents. What this trial shows is the value of bone-protecting agents in this patient population.”

Ancestral characterization of the genomic landscape, comprehensive genomic profiling utilization, and treatment patterns may inform disparities in advanced prostate cancer: A large-scale analysis (Abstract 5003);

Association of increased intensity of prostate-specific antigen (PSA) screening in younger African American men with improved prostate cancer outcomes (Abstract 5004).

The large-scale analysis encompasses the largest cohort of patients that defines comprehensive genomic profiling utilization, the genomic landscape, and treatment implications of this profiling across ancestries of patients with advanced prostate cancer.

Through the prostate-specific antigen (PSA) screening trial, a large cohort of African American males aged 40 to 55 years were evaluated. Findings showed that an increased intensity of PSA screening in this subgroup was linked with a reduction in the risk of lethal disease and metastases at diagnosis, as well as a decrease in prostate cancer–specific mortality.

“[In 5003,] African American men were less likely to receive tumor comprehensive genomic profiling earlier in their treatment course, and we were less likely to be treated on clinical trials, which could impact the genomic landscape outcomes and ultimate disparities.

“Finally, in the screening trial for African American men aged 40 to 55 years, data showed that an increased intensity of PSA screening was linked with a reduced risk of metastases at time of diagnosis and decreased prostate cancer–specific mortality, suggesting that PSA screening and early prostate cancer detection may improve outcomes for this patient population.”

GYNECOLOGIC CANCERS

Shannon N. Westin, MD, MPH; associate professor; director, Early Drug Development, in the Department of Gynecologic Oncology and Reproductive Medicine, at The University of Texas MD Anderson Cancer Center

Optimal treatment duration of bevacizumab (BEV) combined with carboplatin and paclitaxel in patients (pts) with primary epithelial ovarian (EOC), fallopian tube (FTC) or peritoneal cancer (PPC): a multicenter open-label randomized 2-arm phase 3 ENGOT/GCIG trial of the AGO Study Group, GINECO, and NSGO (AGO-OVAR 17/BOOST, GINECO OV118, ENGOT Ov-15, NCT01462890; Abstract 5501).

The optimal duration of bevacizumab (Avastin) when used in combination with chemotherapy in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer has remained unclear. In BOOST, results showed that treatment with the VEGFR inhibitor, when given up to 30 months, did not improve PFS nor OS in this patient population. The investigators concluded that 15 months of bevacizumab should remain the standard of care.

“Continuing on the theme from prior ASCO meetings, it would seem that more is not always better. The BOOST trial, presented by Dr Jacobus Pfisterer [of the AGO Study Group & Gynecologic Oncology Center in Kiel, Germany], revealed that additional cycles of frontline bevacizumab maintenance did not improve progression-free or overall survival in advanced-stage ovarian cancer.”

Maintenance vigil immunotherapy in newly diagnosed advanced ovarian cancer: Efficacy assessment of homologous recombination proficient (HRP) patients in the phase IIb VITAL trial (Abstract 5502).

Vigil immunotherapy is an autologous tumor cell vaccine comprised from autologous harvested tumor tissue; it is transfected with a DNA plasmid encoding GMCSF and bi-shRNA-furin, which leads to control of TGF-β expression. Findings from the VITAL trial showed that, when given as a frontline maintenance treatment in patients with stage III/IV disease, Vigil is safe and has clinical benefit, including those who are BRCA wild-type and homologous recombination (HR) proficient.

“Results from the [VITAL] study were quite exciting! The finding of improved recurrence-free and overall survival in women with HR-proficient ovarian cancer treated with the Vigil vaccine warrants further exploration in a randomized phase 3 study.”

LUNG CANCER AND BEYOND

David Spigel, MD, chief scientific officer, Sarah Cannon Research Institute

IMpower010: Primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC; Abstract 8500).

In stage II to IIIA non–small cell lung cancer (NSCLC), adjuvant atezolizumab (Tecentriq) led to a significant improvement in DFS compared with best supportive care, particularly in those with PD-L1–positive tumors. The findings of the phase 3 study were presented during a virtual press briefing ahead of the 2021 ASCO Annual Meeting.

"This study demonstrates that immunotherapy, and chemotherapy, improves survival for patients with resected NSCLC. These results will introduce immunotherapy into the standard care of resectable lung cancer, which will be a major shift in care for patients and the field."

OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer (Abstract LBA1).

As mentioned previously, the double-blind, phase 3 OympiA study is exploring adjuvant olaparib compared with placebo as an adjuvant treatment for patients with BRCA-mutated, high-risk HER2-negative early breast cancer. The late-breaking research is highly anticipated in the oncology community.

"OlympiA was designed to test the benefits of olaparib following chemotherapy for early-stage BRCA-mutant (high-risk) breast cancer. This has major implications in the care of women with BRCA-mutant breast cancer, which accounts for approximately 5% of all breast cancer."

Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer: VISION (Abstract LBA4).

As mentioned above, the VISION trial is slated to be a heavily discussed abstract in this year's meeting and how it could change clinical practice in prostate cancer with the potential addition of lutetium-177-PSMA-617.

"The VISION study will establish the new role of a radioligand [177 Lu-PSMA-617] in targeting PSMA-positive metastatic prostate cancer. These survival data are significant and will impact care everywhere for patients fighting prostate cancer."

Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: KEYNOTE 564 (Abstract LBA5).

KEYNOTE-564 is another late-breaker abstract, as described above, evaluating pembrolizumab in a setting of RCC for which there are currently no standard therapies.

"KEYNOTE-564 is the trial we have been waiting on, as it will answer the question as to whether immunotherapy following resection of kidney cancer benefits patients. Immunotherapy is firmly established as the up-front treatment for stage IV disease, but its role in early-stage RCC is unknown. This interim analysis shows that adjuvant pembrolizumab vs placebo improves disease-free survival—a critical endpoint. Overall survival is still not mature, but this is a strong signal of benefit."

MULTIPLE MYELOMA

Sagar Lonial MD, FACP, chief medical officer of Winship Cancer Institute, as well as the Anne and Bernard Gray Family Chair in Cancer and professor and chair, Department of Hematology and Medical Oncology at Emory University School of Medicine

Carfilzomib-based induction/consolidation with or without autologous transplant (ASCT) followed by lenalidomide (R) or carfilzomib-lenalidomide (KR) maintenance: Efficacy in high-risk patients (Abstract 8002).

Activity has previously been observed with the combination of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone followed by transplant in patients with multiple myeloma, as seen in the FORTE trial⁹, and this analysis of the pivotal study specifically looked at the effect this regimen had on high-risk and double-hit patients with myeloma. This year, results showcased its effectiveness in both of these subgroups, in addition to those with standard-risk disease.

“Management of high-risk multiple myeloma is a challenge, and this trial helps support what many of us believe is important for improving PFS for these patients, the use of triplet induction, transplant and IMiD/PI maintenance. This should help support a new standard of care for these patients.”

Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 2 (Abstract 8004).

The second part of the CASSIOPEIA study looked at patients with transplant-eligible, newly diagnosed multiple myeloma who received 4 cycles of induction treatment followed by 2 cycles of either daratumumab (Darzalex) plus bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone (VTd) or VTd alone. Patients who received at least a partial response were rerandomized to daratumumab for up to 2 years or observation until disease progression. In the interim analysis, investigators looked at efficacy safety following 281 PFS events.

Findings showed that the maintenance treatment with daratumumab had a clinical benefit in this patient population.

“While not the ideal design for a trial, it has the potential to help address if daratumumab offers benefit both with induction and maintenance. The suggestion that one only needs to see daratumumab either at induction or maintenance [phases] may be a very important result for patients and our community overall.”

Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1 (Abstract 8005).

Ciltacabtagene autoleucel (cilta-cel) has shown impressive response rates in patients with relapsed/refractory myeloma in the phase 1/2 CARTITUDE-1 trial, specifically a 96.9% ORR when delivered at the recommended phase 2 dose; this included a 67.0% stringent complete response (sCR) rate, a 25.8% very good partial response (VGPR) rate, and a 4.1% partial response rate.¹⁰ In May 2021, the FDA granted a priority review designation to the biologics license application for cilta-cel as a treatment of patients with relapsed/refractory multiple myeloma.

The data presented at the 2021 ASCO Annual Meeting will highloght the activity with cilta-cel at a median 12.4 months of follow-up, with an emphasis on early, deep, and durable responses in patients with heavily pretreated patients.

“Is there really a difference between BCMA CAR T-cell products? Cilta-cel investigators seem to think so. This dataset can help sort out if there are differences that impact outcomes broadly.”

Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM; Abstract 8007).

Teclistamab has demonstrated activity in patients with relapsed/refractory myeloma, which showed a 73% ORR, a very good partial response rate of 55%, and a complete response (CR) rate or better of 23%, all at the recommended phase 2 dose.¹¹ Updated results will look further at teclistamab with longer follow-up at the recommended phase 2 dose.

“CAR T-cell therapy vs bispecific is the question of the day in multiple myeloma. At this meeting, there are several examples of BCMA bispecifics that look very promising. This study helps us understand the benefit in one of the largest data sets reported to date.”

Updated results of a phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM; Abstract 8008).

The bispecific antibody talquetamab is another novel agent that demonstrated encouraging antitumor activity in the relapsed/refractory multiple myeloma population. In findings presented during the 2020 ASH Annual Meeting and Exposition, which was at a median follow-up of 3.7 months, talquetamab led to a 69% ORR in 13 patients who had received the recommended phase 2 dose of 405 µg/kg delivered subcutaneously.¹² The median time to the first confirmed response was relatively short, at 1 month (range, 1-2).

The updated phase 1 results will highlight the efficacy at longer follow-up of recommended phase 2 dose in this patient population.

“Is there more than BCMA? Talquetamab data from this abstract says ‘yes!’ It is very exciting to have more than just CD38, SLAMF7, and BCMA as immune targets for multiple myeloma.”

PER®’s Oncology Now Series will feature 21 activities across malignancies with additional experts in cancer care highlighting their perspectives on the data presented at the Annual Oncology Meeting. Register now to attend.

References

1. IDMC has concluded that OlympiA trial of Lynparza crossed superiority boundary for invasive disease-free survival vs. placebo at planned interim analysis. News release. AstraZeneca. February 17, 2021. Accessed February 17, 2021. http://bit.ly/2NgJfTN
2. Nitz UA, Christgen M, Kates R, et al. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR− phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel. Ann Oncol. 2017;28(11):2768-2772. doi:10.1093/annonc/mdx494
3. Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30(8):1279-1288. doi:10.1093/annonc/mdz158
4. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384(13):1191-1203. doi:10.1056/NEJMoa2032125
5. Andre T. Shiu Kai-Keen, Kim TW, et al. Pembrolizumab in microsatellite-instability–high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207-2218. doi:10.1056/NEJMoa2017699
6. Siena S, Bartolomeo MD, Raghav K, et al. A phase 2, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-expressing metastatic colorectal cancer: DESTINY-CRC0 J Clin Oncol. 2020;38(suppl 15; abstr 4000). doi:10.1200/JCO.2020.38.15_suppl.4000
7. Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer. Press release. Novartis. March 23, 2021. Accessed May 27, 2021. https://bit.ly/3hYpaP7
8. Merck’s Keytruda (pembrolizumab) demonstrated superior disease-free survival (DFS) compared with placebo as adjuvant therapy in patients with renal cell carcinoma (RCC) following surgery. News release. Merck. April 8, 2021. Accessed May 27, 2021. https://bit.ly/3vpWdzw
9. Gay F, Cerrato C, Petrucci MT, et al. Efficacy of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma according to risk status: Results from the FORTE trial. J Clin Oncol. 2019;37(suppl; abstr 8002). doi:10.1200/JCO.2019.37.15_suppl.8002
10. Madduri D, Berdeja JG, Usmani SZ, et al. CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in relapsed/refractory multiple myeloma. Blood. 2020;136(suppl 1):22-25. doi:10.1182/blood-2020-136307
11. Garfall AL, Usmani SZ, Mateos M-V, et al. Teclistamab, a B-cell maturation antigen (BCMA) X CD3 bispecific antibody, in relapsed and/or refractory multiple myeloma (RRMM): updated phase 1 results. Presented at: 2nd European Myeloma Network Meeting; March 3-6, 2021; virtual. Abstract B11.
12. Chari A, Berdeja JG, Oriol A, et al. A phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) x CD3 bispecific antibody, in patients with relapsed and/or refractory multiple myeloma (RRMM). Blood. 2020;136(supp 1):40-41. doi:10.1182/blood-2020-133873