2022 Year in Review: New Treatments, Technologies &… : Oncology … – LWW Journals
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Nalley, Catlin
The field of oncology has seen tremendous growth and advancement in recent years, and 2022 is no exception. From a plethora of FDA approvals to practice-changing research breakthroughs, the momentum continues. As the year comes to a close and we move into 2023, Oncology Times spoke with experts in various specialties to reflect on the progress that has been made, lessons learned, and their perspectives on the future.
Over the course of the last year, there have been a number of breakthroughs with significant implications for cancer research and treatment.
Findings from a prospective, Phase II study, which were presented at the 2022 ASCO Annual Meeting and published in the New England Journal of Medicine, demonstrated a clinical complete response in all 14 patients who received the immunotherapy dostarlimab as a first-line treatment for mismatch repair-deficient (MMRD) locally advanced rectal cancer (2022; doi: 10.1056/NEJMoa2201445).
Single-agent dostarlimab, an anti-PD-1 monoclonal antibody, was given to patients every 3 weeks for 6 months in patients with mismatch repair-deficient Stage II and III rectal adenocarcinoma, to be followed by standard chemoradiation and surgery. Patients who achieved a clinical complete response were eligible for omission of chemoradiation and surgery, according to the researchers.
“While longer follow-up is needed to assess response duration, this is practice-changing for patients with MMRD locally advanced rectal cancer,” said study author Luis Alberto Diaz, Jr., MD, Head of the Division of Solid Tumor Oncology, in a statement.
In breast cancer, a Phase III study showed that trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy among patients with HER2-low metastatic breast cancer (N Engl J Med 2022; doi: 10.1056/NEJMoa2203690). Up until this point, currently available HER2-directed therapies have proven ineffective in patients with these “HER2-low” cancers. Results from this study could have a significant impact on this patient population and represent a new standard of care.
This study led to the FDA approval of trastuzumab deruxtecan in August 2022 for adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.
There was also progress in the research and treatment of lung cancer with multiple FDA approvals. For instance, tremelimumab was approved in combination with durvalumab and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) who had no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
Cemiplimab-rwlc in combination with platinum-based chemotherapy was approved for adult patients with advanced NSCLC with no EGFR, ALK, or ROS1 aberrations based on findings from Study 16113, a randomized, multicenter, multinational, double-blind, active-controlled trial in 466 patients with advanced NSCLC who had not received prior systemic treatment.
The field of prostate cancer is an area of oncology that has seen significant growth and advancements in 2022. One of the most important developments, according to City of Hope’s Tanya Dorff, MD, is the FDA approval of lutetium Lu 177 vipivotide tetraxetan for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.
At the same time, the FDA approved gallium Ga 68 gozetotide, a radioactive diagnostic agent for positron emission tomography (PET) of PSMA-positive. This is the first radioactive diagnostic agent approved for patient selection in the use of a radioligand therapeutic agent, according to the FDA.
“It’s a new class of drug and new way of thinking about, seeing, and treating prostate cancer, and obviously can have significant impacts on survival,” said Dorff, who is a medical oncologist specializing in prostate cancer and Section Chief in the Genitourinary Disease Program at City of Hope.
“And then, the other big story continues to be in the metastatic hormone-sensitive prostate cancer setting where using drugs earlier has had such a huge impact on long-term cancer control,” she continued. “This year, the story really is evolving around triplet therapy versus doublet therapy.”
In terms of technology, Dorff discussed the growing impact of PSMA PET scans. “While this technology has been around for a while, access has been limited until recently,” she explained. “As we gain access to this tool, there is a steep learning curve to understand how to apply it in clinical practice and interpret the results. This, in my opinion, has been the biggest technologic disrupter this year.”
There is also a growing body of data regarding the use of artificial intelligence, primarily in pathology, to help with cancer detection and grading, Dorff said. “This is an emerging story that we are going to hear more about in the future.”
While discussing lessons learned from 2022, Dorff said, “all the research in the world doesn’t help patients unless the information gets disseminated and then physicians adopt the new practices or the new agents, and that we actually have access to them.
“This is the big lesson from this year,” she emphasized. “We have patients whose physicians don’t recommend, for instance, intensified therapy up front or, when they do, the insurance company denies the drug or there is too high a copay.”
Another example of this includes the challenges often associated with ordering a PET scan so a patient can qualify for the new FDA-approved drug. “We either can’t get the PET scan or there isn’t enough of the agent produced,” Dorff said. “So, it’s really important that, along with research and regulatory approval, there’s an emphasis on access and education to ensure patients are able to benefit from these treatment advances.”
Looking to 2023, Dorff believes there will be more clarity around the use of PARP inhibitors—which are currently approved for patients whose genomics or germline sequencing identify specific mutations—in unselected populations of prostate cancer patients. “Additional data in this area will be really important to help inform us on how to change our practice and whether to start using these agents in combinations in a broader group of prostate cancer patients,” she said.
“Moving forward, my number one message always is that we need to be thinking about clinical trials in all phases of the disease because that’s how we make the biggest impact,” Dorff told Oncology Times. “Additionally, it can be difficult to move away from our paradigms that have been ingrained into our practice, and a lot of people still want to hold treatments in reserve for prostate cancer rather than using double or triple therapy upfront. However, the benefits really show that there’s a difference to using them right away versus waiting and using them sequentially later.”
There have been a number of advancements in radiation oncology in 2022 and Jeff Michalski, MD, MBA, FASTRO, ASTRO’s President and one of the leaders of the NRG Oncology trials group, is looking forward to ongoing progress as we enter 2023.
An exciting development, which has been gaining momentum over the last few years, is prophylactic radiation therapy for asymptomatic osseous oligometastases. A recent multicenter, randomized Phase II trial demonstrated that adding prophylactic bone lesion radiotherapy to standard care appears to be a safe and effective for the prevention of skeletal side effects in patients with solid tumors (NCT03523351; ASTRO 2022 Annual Meeting, Abstract LBA4). Although not a primary endpoint, the study authors also observed an improvement in overall survival. “This is a very exciting avenue of research and the hope is to conduct a larger clinical study to validate these results,” said Michalski, who is also Vice Chair and Director of Clinical Programs in Radiation Oncology at Washington University School of Medicine in St. Louis.
This year also saw further developments toward shorter courses of radiation therapy in several different cancer types, according to Michalski, who highlighted a study presented at the ASTRO 2022 Annual Meeting. This randomized, Phase III study showed that high-risk prostate cancer can be treated with 5versus 8 weeks of radiation therapy (NCT01444820). It is the first randomized trial to confirm the safety and efficacy of a moderately shortened course of radiation exclusively for patients with high-risk disease, Michalski noted.
Another area that is emerging in radiation oncology is the role of artificial intelligence. The ASTRO theme for 2022 was “AI and EI: Caring for the Patient in a Wireless World,” and a number of related studies were presented during the annual meeting. For example, a team of NRG Oncology investigators conducted an analysis of clinical and digital histopathology data from five Phase III prostate cancer trials to develop and validate multimodal artificial intelligence models (MMAI). They found that the MMAI histopathology models outperformed the NCCN Clinical Practice Guidelines in Oncology when predicting prognosis (Abstract 2).
The human element of clinical care remains an important focus as well, Michalski emphasized, while highlighting a study that demonstrated the value of patients meeting with a medical physicist who can explain how radiation therapy is planned and delivered. This randomized, Phase III clinical trial suggests that this approach reduces patient anxiety and increases patient satisfaction throughout the treatment process (ASTRO 2022 Annual Meeting, Abstract 7). “I think our physicists were very proud to see that their role is being recognized in a very meaningful human fashion,” Michalski said.
Moving into 2023, patient-centric care will remain the focus. The theme for next year’s ASTRO meeting is “Pay it Forward, Partnering with Our Patients,” and Michalski aims to emphasize the important role clinical trials have played in reducing the burden of cancer and improving outcomes for patients. “I hope to include patient voices, particularly those who’ve been part of clinical trials, to talk about their experience so that we can both hear from them and thank them for their contribution,” he said.
“Another important focus is diversity in clinical trial enrollment. It’s critical that our trial populations reflect the population of the communities where we work. Otherwise, we won’t know that these outcomes that we are reporting are generalizable to the community at large,” Michalski continued. “There must also be diversity among investigators and clinical trial leadership.”
Over the course of the last year, the blood disease and cancer space has seen significant growth and advancements. Naveen Pemmaraju, MD, Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, highlighted some of the biggest developments of 2022.
“Number one is the advancement of a gene therapies and new approaches to benign or noncancerous blood diseases that have been very deadly,” he told Oncology Times. “Number two, in the blood cancer space itself, we have seen the continued development of immunotherapy. This includes CAR T, antibody-drug conjugates, and now, very importantly, bispecific antibodies, such as teclistamab in multiple myeloma.
“And then the third category is the continued development of oral targeted therapies in blood cancers, particularly in acute leukemias, such as AML where just a decade ago all the drugs were IV,” he added. “When you look at these types of breakthroughs that have occurred just in the last 12-14 months, it’s breathtaking.”
Pemmaraju also discussed technology advances, specifically improvements in CAR T-cell therapy. “A lot of this technology didn’t even exist 5-10 years ago,” he said. “And the advancements we are witnessing just shows you how rapidly technology is developing that used to be solely in the domain of the research lab and now is starting to come into the clinical sphere.”
There were a few key FDA approvals that were particularly impactful for the blood cancer field. For example, the approval of pacritinib for the treatment of adults with intermediate- or high-risk primary or secondary myelofibrosis with a platelet count below 50 × 109/L was a significant development. Pacritinib—a novel oral kinase inhibitor with specificity for JAK2 and IRAK1, without inhibiting JAK1—is the first approved therapy specifically for the needs of cytopenic myelofibrosis patients.
“This is a really important approval in the myelofibrosis field and highlights that breakthroughs can occur in rare diseases,” Pemmaraju said. “With continued study and approach, we can find new drugs and approaches.”
Another important drug approval is teclistamab for multiple myeloma. As the first bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, this agent was granted accelerated approval in October 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, according to the FDA.
Progress was also made in rare blood cancers with the approval of pemigatinib for adult patients with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement. This approval was based on FIGHT-203, a multicenter open-label, single-arm trial that included 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement. Among all patients (including three patients without evidence of morphologic disease), the complete cytogenetic response rate was 79 percent, according to the data.
“Some acute leukemias, such as ALL, are experiencing high cure rates with a total therapy approach, particularly in the frontline setting. There is a focus on the rare and ultra-rare diseases such as BPDCN. And there have been developments in AML, which range from antibiotic prophylaxis to improvement in stem cell transplant to augmentation of regimens into doublets and triplets,” Pemmaraju said while summarizing other advances in blood cancers. “We have seen all of this in 2022. This is an exciting time for researchers and it’s an exciting time for our patients.”
When asked what his message is for the oncology community as a whole, Michalski said, “Cancer is a problem that requires numerous disciplines and partners, and we can’t neglect the information that patients themselves give us.
“We are seeing more patient advocates involved in clinical trial design, which has been enormously helpful. However, we have to find ways to encourage patients to partner with us in research,” he added.
“We can’t let ourselves get too far away from the human element. We must listen to and understand our patients’ concerns and be able to meet the patients where their problems are and not have patients meet us where we believe our solutions are.”
As we begin a new year, it is important to not only look forward, but learn and grow from the past as well. “As we step back and think about the future, we have to consider the lessons learned from the COVID-19 pandemic,” Pemmaraju said.
This includes new areas of science and research, but we need to also look at the bigger picture and examine what worked and what didn’t work during the pandemic for our patients and patient care. Some questions to ask, according to Pemmaraju, include: Do remote and online visits work? And for what patients? How do we optimize telehealth? When conducting clinical trials, what’s required at the center versus what can be done remotely?
“And, as we expand into the next 3-5 years, we have to ask ourselves, what research programs or studies were affected by the pandemic? What studies and research trials were able to continue going and why? This has to go hand in hand with how we think about 2023 because the last few years have been so profound and life-changing for many of us,” Pemmaraju concluded.
“We would be remiss if we didn’t spend some time reflecting and thinking on how the last few years have affected cancer care and clinical trials research, not just adversely, but what things can we take out of it that can positively influence the coming few years?”
Catlin Nalley is a contributing writer.
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