Some of the most exciting new data at this year’s congress included advancements in lung cancer, breast cancer, genitourinary cancers, and gastrointestinal cancers. Several experts spoke with Targeted Oncology to share their thoughts on some of the most impactful abstracts from the 2020 ESMO Congress.
The European Society for Medical Oncology (ESMO) recently hosted its annual congress, remaining dedicated to supporting oncology professionals to ensure patients with cancer are receiving the best possible care despite the challenges of converting to a virtual meeting due to coronavirus disease 2019 (COVID-19).
In an effort to offer a more targeted experience for attendees with the unprecedented virtual platform, ESMO split their virtual congress into 2 parts, which included the science weekend held on September 19–21 and the education weekend, being held on October 16–18. The science portion of the meeting led to the presentation of over 80 late-breaking abstracts, 12 simultaneous publications, and 500 speakers.
“The science meeting was a tremendous digital meeting and the interplay between recorded sessions and live discussions went very well,” Benedikt Westphalen, MD, of the University of Munich in Germany, told Targeted Oncology. “I hope that we learn from these positive experiences, expand during the upcoming ESMO educational weekend, and will integrate our learnings into future conferences to offer both a gratifying digital and in-person experience to move to real hybrid events once the COVID-19 situation has passed.”
The purpose of this congress is to pave the way for new treatment options and to disseminate the latest science from the field. ESMO’s mission is to support members of the global oncology community. The transition to a new virtual format was also fitting for this year’s tagline, “Bringing Innovation to Cancer Patients.”
“We adapt to the situation we're in, and I think the virtual format allows us to still get that information out, and these practice-changing trials out for everyone to appreciate and understand better,” Bradley McGregor, MD, of the Dana-Farber Cancer Institute, told Targeted Oncology.
“The commitment to provide better cancer care and to improve the quality of life of cancer patients has been unchanged,” Claudia Cardone, MD, PhD, of the Instituto Nazionale Tumori, in Italy, said in an interview with Targeted Oncology. “Despite the novel format, the 2020 ESMO Congress was a highly interactive meeting where participants had the opportunity to interact and engage in live discussions in the virtual platform and to connect through social media by using the official hashtag [#ESMO20].”
Antonio Passaro, MD, PhD, of the European Institute of Oncology in Italy, was in agreement over how well this year’s meeting turned out. He told Targeted Oncology, “Personally, I think that this ESMO meeting was a great success. Despite the pandemic, this meeting was perfect in the virtual format thanks to all of the ESMO staff who worked behind the scenes and remotely [to put on] a great program of a very high scientific level. [However], we know it’s not like face-to-face conferences.”
Converting to the novel virtual format is a great example of how well the field is able to adapt and continue to innovate cancer research, but there are some things that many oncologists look forward to experiencing again when in-person meetings are plausible.
“What I missed the most was face-to-face networking, [which is] crucial for career development in young oncologists,” Cardone said. “I hope the digital evolution forced by the COVID-19 pandemic will continue in the future and be implemented in the face-to-face interaction of live conferences when [it’s safe to do so].”
“I always tell younger investigators to go to these meetings and learn from the leaders firsthand, which is not possible through virtual meetings, or at least is very difficult when you don't have that component of human interaction,” Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, told Targeted Oncology. “Having said that, I think there are benefits to a virtual meeting. You get to decrease the carbon footprint and stay in your house. You don't need to travel, and you save more time, so you can be with your family. I think there are pros and cons, but personally, I like in-person meetings more.”
Although opinions on the virtual meeting format vary, many experts will agree that this year’s meeting brought forward a huge number of advancements from across all the data that were presented. In a poll on Twitter, Targeted Oncology asked, in what area do you think the most important data came from at the 2020 ESMO Congress?
Some of the most exciting new data at this year’s congress included advancements in lung cancer, breast cancer, genitourinary (GU) cancers, and gastrointestinal (GI) cancers. Several experts spoke with Targeted Oncology to share their thoughts on some of the most impactful abstracts from the 2020 ESMO Congress.
“I think that the message for patients is that we haven't stopped, we carry on. The results are coming through,” Daniel A. Vorobiof, MD, medical director at Belong.Life, told Targeted Oncology.“We have new drugs, new combinations, new good treatments, just different circumstances.”
Many advancements in lung cancer were also brought up during the meeting as well. In particular, targeted agents continue to demonstrate promising efficacy and safety in patients with lung cancer.
“First of all, almost one-third of patients with metastatic non–small cell lung cancer (NSCLC) and PD-L1 ≥50% are alive at 5 years when treated with pembrolizumab (Keytruda; KEYNOTE-024). This is amazing progress for all of us that every day are treating [patients with] lung cancer,” said Passaro. “In addition to the great survival improvement achieved with the targeted agents, these results confirmed, once again, that research matters and that lung cancer no longer appears to be an incurable disease, although there is still a long way to go.”
“The CROWN trial, which evaluated untreated patients with ALK-rearranged stage IIIB/IV NSCLC, showed that lorlatinib (Lorbena) significantly improved progression-free survival (PFS), the primary end point, compared with the non-actual standard crizotinib (Xalkori) with an impressive PFS-HR of 0.28 (P <.001),” said Passaro. “All the efficacy endpoints were significantly in favor of lorlatinib confirming the high efficacy of the third-generation tyrosine kinase inhibitor (TKI) of ALK, also for intracranial response and duration of response.
“Although, the discontinuation rate was similar between the 2 arms (6.7% vs 9.2% in favor of lorlatinib), the incidence of adverse events of grade 3/4 was higher with lorlatinib than crizotinib (72.5% vs 55.6%), supporting the doubts of long-term treatment management, potentially affecting the quality of life,” Passaro noted. “However, these results undoubtedly confirm and accept lorlatinib among the new generation inhibitors, which can be used in the first line to improve the outcomes of our patients.”
Osimertinib (Tagrisso) reduced the risk of central nervous system (CNS) death or progression by 82% as treatment of patients with early-stage EGFR-mutant NSCLC following complete tumor resection in the ADAURA study, which was simultaneously published in the New England Journal of Medicine.
“ADAURA was presented with the results of the site progression that confirmed, as expected, that adjuvant osimertinib reduced the risk of CNS recurrence (HR, 0.18),” said Passaro. “Among patients treated with osimertinib, 62% developed a local or regional recurrence, and the remainder reported distant recurrences (38%). After a median of 22 months of follow-up, the CNS recurrence rate was 1% among the patients who received osimertinib and 10% among those who received placebo. These results reinforce the role of adjuvant osimertinib in EGFR-positive patients that received a radical surgery, though these data are still immature, reporting only 7% of maturity.”
In patients with advanced EGFR-mutant NSCLC who were either treatment-naïve or osimertinib-resistant, the phase 1 CHRYSALIS study demonstrated high response rates with the novel combination of amivantamab (JNJ-61186372; JNJ-6372) and lazertinib. The regimen also appeared to have a favorable safety profile.
“Another deserved mention, the CHRYSALIS study is evaluating the combination of amivantamab, an EGFR- and MET-targeting antibody, in combination with a third-generation EGFR TKI, lazertinib, in patients with NSCLC harboring common EGFR mutations in the resistant and naïve settings,” Passaro said. “Among osimertinib-resistant patients, the combination showed an interesting objective response rate (ORR) of 36%, while in the treatment-naïve group (n = 20), the combination achieved an ORR of 100%. These data are preliminary, but of course are intriguing looking forward for the EGFR-mutant disease.”
Patients with completely resected stage IIIAN2 NSCLC should not be recommended for post-operative radiotherapy (PORT) due to a nonstatistically significant increase in disease-free survival compared with those treated in the control arm, according to findings from the phase 3 LungART study.
“These important results confirmed that PORT cannot be recommended for patients with mediastinal nodal involvement after surgery,” Passaro said. “Considering the risk of over-added cardio-pulmonary toxicity related to PORT and the survival results, to date we can confirm that PORT after radical surgery shouldn’t be recommended as standard of care though some patients treated with PORT showed a decreased rate of mediastinal relapse by 50%.”
During the 2020 ESMO Congress, a number of studies were presented in the breast cancer field, but some of the most exciting data in this space revolved around targeted therapies. Several agents demonstrated promising data in clinical trials across a variety of subgroups of patients with breast cancer.
“There was good new data in breast cancer, and there were some less good or maybe contrasting results in some of the trials,” said Vorobiof. “I think from the breast cancer point of view, there were [many] interesting data, and some of them will become standard treatments, in the near future.”
In the phase 3 SOLAR-1 study, postmenopausal patients with PIK3CA-mutant, hormone receptor (HR)–positive, HER2-negative advanced breast cancer experienced prolonged overall survival with alpelisib (Piqray) in combination with fulvestrant, despite not crossing the prespecified O’Brien-Fleming efficacy boundary (P ≤.0161).
“This study showed significant improvement in the progression-free survival and overall survival in this group of patients which harbor the PIK3CA mutation. Usually, these patients might have a poor prognosis or have built up endocrine resistance, so after a period of time, they are not responding to the first-line endocrine treatment,” Vorobiof said. “Therefore, these new data are promising as options for these patients are quite limited.”
The combination of abemaciclib (Verzenio) plus tamoxifen improved overall survival (OS) compared with abemaciclib alone as treatment of patients with HR-positive, HER2-negative metastatic breast cancer, according to findings from the final OS analysis of the nextMONARCH study.
The benefit for the combination was observed across all subgroups in the study. The adverse events were similar to those observed in the primary analysis, as well as the known safety profile of abemaciclib.
Neoadjuvant atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) plus doxorubicin and cyclophosphamide significantly improved pathologic complete responses (CRs) compared with placebo and chemotherapy as treatment of patients with stage 2 or 3 triple-negative breast cancer in the phase 3 IMpassion031 study. These findings were simultaneously published in The Lancet, as well.
“This study was for patients with early triple-negative breast cancer, so patients did not have metastatic disease,” said Vorobiof. “The results are encouraging with the use of atezolizumab and nab-paclitaxel before surgery, so it's neoadjuvant treatment, and regardless of the PD-L1 status of the patient. These treatments significantly improve the pathological complete response with an acceptable toxicity profile. This is very good news coming from the meeting.”
The 2020 ESMO Congress shared many exciting abstracts in the field of GU cancers. Some of these advances included practice-changing data in the fields of bladder and prostate cancers, but exciting new data were also shared for patients with advanced kidney cancer that are expected to change the standard of care.
“Therapy for renal cell carcinoma continues to evolve, and we now have 4 different options to be utilized in the frontline setting,” said McGregor. “I look forward to ongoing trials to better improve upon these outcomes in the frontline setting, while at the same time looking for ways to improve therapy for those patients who don't respond or who stopped responding with novel combinations and novel drugs.”
The frontline combination of nivolumab (Opdivo) and cabozantinib (Cabometyx) led to a 49% reduction in the risk of disease progression or death as treatment of patients with advanced renal cell carcinoma in the phase 3 CheckMate-9ER study. The combination also significantly improved the OS and doubled the ORR.
“From a renal cell carcinoma standpoint, [CheckMate-9ER] by far stood out above the rest, and that's why it was 1 of the presidential symposiums,” McGregor said. “I think this becomes standard of care. This just gives us another standard of care for those patients who present with a new diagnosis of metastatic renal cell carcinoma.”
Avelumab (Bavencio) in combination with best supportive care as frontline maintenance improved both PFS and OS in patients with advanced or metastatic urothelial carcinoma who had not progressed on frontline platinum-based chemotherapy, according to the final analysis from the phase 3 JAVELIN Bladder 100 study.
“What we saw was striking. The magnitude of OS benefit we saw with frontline maintenance therapy with avelumab, I don't think we have seen this kind of OS benefit with any agent or any class of drug in metastatic urothelial carcinoma, especially in this setting,” said Agarwal. “In my clinic, this is considered 1 of the most preferred regimens for my patients.”
Olaparib (Lynparza) induced a significantly longer duration of OS compared with enzalutamide (Xtandi) or abiraterone acetate (Zytiga) plus prednisone in men with metastatic castration-resistant prostate cancer (mCRPC), harboring at least 1 alteration in BRCA1, BRCA2, or ATM and disease that has progressed during previous treatment with a next-generation hormonal agent, according to the updated findings from the randomized phase 3 PROfound study.
“The PROfound trial was the first positive phase 3 trial in mCRPC, where patients are selected based on biomarkers. That is what makes the trial so special,” Agarwal said. “It is very exciting to see these kind of trials happening in patients with prostate cancer and that we, for the first time, have a reason to test these patients. Given that we have a very efficacious and well-tolerated oral pill available in the clinic now for these patients who are harboring DNA repair gene–related mutations in the tumors, there is no reason now to not test these patients the first time when we see them.”
Data in the GI cancer space at this year’s meeting will impact the treatment of patients with colorectal cancer (CRC), gastric/gastroesophageal junction (G/GEJ) cancer, and esophageal cancer, among others.
“By far, the most impactful abstracts in GI oncology are the results from the CheckMate 649, ATTRACTION-4, CheckMate 577, and KEYNOTE-590 as they will have a major impact on the treatment of patients with upper GI cancers,” Westphalen said. “These will most probably change standard of care.”
Although there were many new updates in this space, Westphalen and Cardone selected a few abstracts, in particular, that stood out among other data that were presented in GI cancers at the 2020 ESMO Congress.
“Luckily, we are continuing our path forward with novel therapeutics for molecularly defined subgroups of patients,” said Westphalen. “I am hopeful that we will see ever more modern targeted agents in clinical trials to expand our therapeutic portfolio across malignancies.”
Cardone also noted data from the KEYNOTE-177 study were very exciting as well; this was a phase 3 study that demonstrated clinically meaningful improvements in the health-related quality of life of patients with microsatellite instability-high and/or mismatch repair-deficient metastatic CRC compared with frontline pembrolizumab compared with standard of care chemotherapy.
Frontline pembrolizumab with chemotherapy demonstrated a significant improvement in OS, PFS, and ORRs compared with chemotherapy alone in patients with locally advanced unresectable or metastatic esophageal cancer, according to the phase 3 KEYNOTE-590 study (NCT03189719).
“The KEYNOTE-590 trial examined first-line chemotherapy, with or without pembrolizumab, in patients with squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus, or Siewert type 1 GEJ adenocarcinoma,” said Cardone. “[These data] demonstrate that pembrolizumab plus chemotherapy improved OS in patients with squamous cell carcinoma of the esophagus with PD-L1 Combined Positive Score [CPS] >10 tumors, all squamous cell carcinomas, all patients with CPS >10, and the study population as a whole.”
Nivolumab in combination with chemotherapy induced a statistically significant improvement in the PFS as treatment of patients with previously untreated advanced or recurrent G/GEJ cancer, and the combination also elicited higher overall responses in the phase 2 ATTRACTION-4 study.
“[This study was] performed only in Asian patients, and the primary end points were designed for all-comers, rather than a specific CPS value,” Cardone said. “First-line treatment with nivolumab plus chemotherapy improved the co-primary PFS endpoint, but not overall survival.”
The frontline use of nivolumab with chemotherapy induced a statistically significant survival benefit compared with chemotherapy alone in patients with newly diagnosed PD-L1–positive advanced G/GEJ cancer and esophageal adenocarcinoma.
“CheckMate 649 evaluated nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment in patients with non–HER2-positive adenocarcinoma, advanced G/GEJ cancer, or esophageal cancer with improved OS and PFS in patients with PD-L1 (CPS) >5 tumors,” said Cardone. “Improvements were also observed in patients with PD-L1 CPS >1 tumors and in the overall patient population.”
Peters S. ESMO Virtual Congress 2020 Opening Ceremony. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020; Virtual.