ASCO 2020: Top KOLs Select Vital Studies Ahead of Virtual Meeting

For the first time since 2009, the ASCO Annual Meeting will not be taking place in Chicago, Illinois. Due to the COVID-19 pandemic, the conference has shifted to a virtual platform for its 2020 program.

Nevertheless, thousands of practice-changing abstracts have been released to the oncology community.

Approximately 2215 abstracts were accepted for presentation during this year’s program, and more than 3400 additional abstracts were accepted for online publication. From May 29 to May 31, studies spanning CAR T-cell therapy, immunotherapy and targeted agents, personalized approaches, and much more across a number of cancer types will be highlighted in a digital format.

Ahead of the 2020 ASCO Virtual Scientific Program, we spoke with a handful of leading oncologists in breast cancer, lung cancer, gastrointestinal cancers, genitourinary cancers, and hematologic malignancies to gain their perspectives on the most significant studies in their respective specialties.

­BREAST CANCER

Stephanie L. Graff, MD

Stephanie L. Graff, MD, director of the Breast Program at the Sarah Cannon Cancer Institute of HCA Midwest Health; associate director of the Breast Cancer Research Program at Sarah Cannon Research Institute

Chemotherapy (CT) de-escalation using an FDG-PET/CT (F-PET) and pathological response-adapted strategy in HER2[+] early breast cancer (EBC): PHERGain Trial (Abstract 503)

In patients with HER2-positive early breast cancer, the combination of trastuzumab (Herceptin) and pertuzumab (Perjeta) has shown promising pathologic complete response (pCR) rates, but is said to still be low compared with the addition of chemotherapy. In PHERGain, researchers sought to identify sensitivity markers to trastuzumab/pertuzumab through early metabolic response, by F-PET, in an effort to de-escalate chemotherapy. Results of the study showed that F-PET can identify patients who will likely benefit from a chemotherapy-free approach and receive neoadjuvant treatment with trastuzumab and pertuzumab alone.

“PET is widely available, and if we are able to utilize this tool to de-escalate therapy for persons with breast cancer, it will be an important patient-centered win [by] minimizing side effects. This is the first step.”

Validation of MAF biomarker for response prediction to adjuvant bisphosphonates in 2 clinical trials: AZURE and NSABP-B34 (Abstract 513)

In this analysis of 2 pivotal trials of patients with breast cancer, AZURE and NSAPB-B34, researchers evaluated the levels of MAF amplification in enrolled specimens in an effort to determine whether this can serve as a predictive biomarker of response to adjuvant bisphosphonates.

The exploration of samples in both studies showed that MAF amplification does predict response to adjuvant bisphosphonates, findings of which can be used as evidence toward introducing MAF testing into breast cancer practice.

“Bisphosphonates have a small but significant impact on breast cancer outcomes, but they also come with side effects. Being able to identify the population that gets the biggest benefit would help personalize care.”

Towards data-driven decision-making for breast cancer patients undergoing mastectomy and reconstruction: Prediction of individual patient-reported outcomes at two-year follow-up using machine learning (Abstract 520)

A validated machine learning algorithm was designed to predict individual postoperative breast-satisfaction from mastectomy and breast reconstruction, and ultimately help with individualized data-driven decision making in breast cancer care. Results showed that such algorithms could be appropriate in identifying those who might benefit from alternative treatment decisions than suggested by group-level evidence.

“I find that many women, years after breast surgery, confide in me [with] ‘If I had only known’ sentiments. I think the power of showing someone personalized prediction around breast reconstruction is a really interesting tool. Another patient-centered trial for [the 2020 ASCO Virtual Scientific Program].”

Comprehensive profiling of androgen receptor-positive (AR+) triple-negative breast cancer (TNBC) patients (pts) treated with standard neoadjuvant therapy (NAT) +/- enzalutamide (Abstract 517)

Patients with luminal androgen receptor (AR)–positive triple-negative breast cancer (TNBC) are known to have lower pCR rates following neoadjuvant chemotherapy. In the nonrandomized ARTEMIS trial, patients who had chemotherapy-insensitive TNBC were treated with a regimen of enzalutamide (Xtandi) and paclitaxel (n = 17). Ahead of the presentation, results showed that this approach led to a 33.3% pCR rate (n = 5), suggesting that this type of combination may be one to explore in this patient subtype.

“Any move toward targeting or tailoring treatment in triple-negative breast cancer is exciting.”

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB; Abstract 1005)

The FDA approved tucatinib (Tukysa) in combination with trastuzumab and capecitabine (Xeloda) in April 2020 for adults with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least 1 prior anti–HER2-based regimen in the metastatic setting. The approval was based on findings from the phase 2 HER2CLIMB trial. At the 2020 ASCO Virtual Scientific Program, data specifically from the brain metastasis subgroup of patients will be presented. Results have already shown that the triplet regimen doubled the intracranial objective response rate, reduced risk of intracranial progression or death, and led to a reduction in the risk of death compared with trastuzumab/capecitabine alone.

“This study is so novel in the unique inclusion of brain [metastases]. It is a big step forward for persons with HER2-positive metastatic disease. [I] can’t wait to see the brain metastasis–specific data presented.”

GENITOURINARY CANCERS

Toni Choueiri, MD

Toni Choueiri, MD, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute

Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis (Abstract LBA1)

This late-breaker abstract highlights the statistically significant improvement in overall survival (OS) observed with the combination of the PD-L1 inhibitor avelumab (Bavencio) plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma followed platinum-based chemotherapy in the frontline setting. Based on the JAVELIN Bladder 100 (NCT02603432) findings, the FDA granted a breakthrough therapy designation to avelumab in this setting. 

“The JAVELIN Bladder 100 study of maintenance avelumab is really a very important concept: after giving 4 to 6 cycles of chemotherapy, does maintenance avelumab versus placebo in the phase 3 [setting] result in improved clinical outcomes? There was a very strong OS benefit favoring avelumab with an acceptable safety profile. I expect this drug to be approved in this context hopefully soon for patients, so it is quite important.”

IMvigor010: Primary analysis from a phase III randomized study of adjuvant atezolizumab (atezo) versus observation (obs) in high-risk muscle-invasive urothelial carcinoma (MIUC; Abstract 5000)

In the international, open-label, controlled, phase III IMvigor010 trial, investigators evaluated the efficacy and safety of adjuvant atezolizumab (Tecentriq) compared with observation in 809 people with muscle-invasive bladder cancer who are at high risk for recurrence following surgical resection. In January 2020, a press release noted that adjuvant treatment with the PD-L1 inhibitor did not significantly improve disease-free survival (DFS) versus observation in patients with muscle-invasive bladder cancer, and missed the trial’s primary end point.

“On the other hand, another PD-L1 inhibitor, which is important for practice did not meet its primary end point in a different setting in high-risk bladder cancer. Dr. Maha Hussain presented the data with adjuvant atezolizumab as part of the IMvigor010 trial. This was actually a quite anticipated trial here that did not pan out to be positive.

It was a bit of a blow to the field because we really were thinking about an adjuvant treatment for these patients to replace chemotherapy, but atezolizumab did miss this DFS endpoint in muscle-invasive bladder cancer versus observation. It remains difficult to reduce the risk of muscle-invasive urothelial cancer after surgery. It is important to understand that randomized clinical trials are needed to answer important, big questions [like this].”

Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced renal cell carcinoma (RCC): Updated analysis of KEYNOTE-426 (Abstract 5001)

Earlier data from the KEYNOTE-426 trial, which explored the combination of pembrolizumab (Keytruda) and axitinib (Inlyta) for the frontline treatment of patients with advanced renal cell carcinoma (RCC), led to the approval of this regimen in this setting. At the 2020 ASCO Virtual Scientific Program, findings with longer follow-up, at a median of 27 months, will be presented.

“This combination of pembrolizumab and axitinib did already result in an OS benefit. There was an update with more follow-up, and the study continued to provide an OS benefit with a hazard ratio of 0.68. The hazard ratio seems higher than previously presented with more follow-up, probably due to subsequent lines of therapies.

The interesting thing on the study is that the rate of complete responses (CRs) has increased, and these are the best responses you can wish for. There were no new signs of toxicities. It's cemented again: pembrolizumab and axitinib is a very reasonable first choice in untreated RCC.”

Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260; Abstract 5006)

Optimized management of nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma (RCC): A response-based phase II study (OMNIVORE; Abstract 5005)

Both sequencing-based studies evaluated strategies with the PD-1 and CTLA-4 inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy), respectively. In the phase 2, response-adaptive OMNIVORE trial, investigators evaluated the sequential addition of 2 doses of ipilimumab to induce response in non-responders to nivolumab, as well as the duration of nivolumab in responding patients with advanced RCC.

In HCRN GU16-260, the efficacy and toxicity of single-agent nivolumab was evaluated in patients with advanced RCC, and then also salvage therapy with nivolumab/ipilimumab in patients whose tumors are resistant to initial nivolumab monotherapy.

“The HCRN GU16-260 study, by Dr. Michael Atkins, answers an important question, which is nivolumab sequenced with ipilimumab. These patients started on nivolumab, and then ipilimumab was added based on responses. This will also be presented in the same session as with Dr. Rana McKay—[who led] a similar study and design, except [in HCRN GU16-260 where there were] 4 doses of ipilimumab. In Dr. McKay's study, 2 doses of ipilimumab were given.

The bottom line is, in both studies, there were not many CRs. This made me think that this strategy of [using these agents in] combination may be better. It is also important to inform the practice; I personally would not recommend [sequencing] unless there is really a specific reason. I would not recommend starting [a patient on a] PD-1 inhibitor and adding a CTLA-4 inhibitor, unless there is a reason and an increased potential, theoretical risk of immune-related adverse effects.”

Phase II study of the oral HIF-2α inhibitor MK-6482 for Von Hippel-Lindau disease–associated renal cell carcinoma (Abstract 5003)

In VHL disease–associated RCC, initial results of the open-label, phase 2 study of the HIF-2a inhibitor showed promising efficacy and tolerability in patients with VHL-associated clear cell RCC and responses in other VHL-related lesions, suggesting that the agent can be further explored in VHL disease.

“One interesting study is actually a study in non–clear cell RCC with VHL syndrome with Eric Jonasch, MD, and the HIF-2αinhibitor. During the 2020 Genitourinary Cancers Symposium, we presented the results in metastatic clear cell RCC and, and now it's [being tested] in VHL syndrome. There is quite interesting activity with this well-tolerated HIF-2αinhibitor compound MK-6482. I look forward to seeing even more follow-up and potentially more responses happening. That is another very small subset of patients. This is definitely an unmet need, and it is so good to see a drug developed in this context.”

LUNG CANCER

Stephen Liu, MD

Stephen Liu, MD, associate professor of medicine; director, Thoracic Oncology, Georgetown University

Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA (Abstract LBA5)

The phase 3 ADAURA study evaluated adjuvant osimertinib (Tagrisso) in patients with stage IB, II and IIIA EGFR-mutant non–small cell lung cancer (NSCLC) with complete tumor resection. In April 2020, it was announced that the trial would be unblinded early following a recommendation from an Independent Data Monitoring Committee, which determined there was overwhelming efficacy with the EGFR TKI. Full findings will be presented at the 2020 ASCO Virtual Scientific Program. Osimertinib is currently approved as a frontline treatment for patients with EGFR-mutant NSCLC.

“The ADAURA trial explored the role of adjuvant osimertinib for up to 3 years in patients with resected NSCLC that harbors an EGFR mutation. We have heard the study showed ‘overwhelming efficacy’ and we are eager to see exactly what that means as we see the first results from this potentially paradigm shifting phase III study. What degree of disease-free survival benefit will we observe and is there any early survival data?”

KEYNOTE-604: Pembrolizumab (pembro) or placebo plus etoposide and platinum (EP) as first-line therapy for extensive-stage (ES) small-cell lung cancer (SCLC; Abstract 9001)

In the double-blind, phase III study, the PD-1 inhibitor pembrolizumab was explored in combination with etoposide and platinum-based therapy for treatment-naïve patients with extensive-stage small cell lung cancer (SCLC). Findings showed that the immunotherapy/chemotherapy combination showed a significant improvement in progression-free survival (PFS), but the OS benefit was not found to be significant when compared with placebo and chemotherapy. Additionally, no unexpected toxicities were observed with the addition of pembrolizumab.

“KEYNOTE-604 compared chemotherapy with pembrolizumab versus placebo for patients with extensive-stage SCLC. In the phase III IMpower133 and CASPIAN trials, the addition of the anti–PD-L1 antibody improved OS. We know that this trial did not meet its survival endpoint and we have been waiting to see the data to better understand these results.”

Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE; Abstract 9503)

The immunomodulatory receptor TIGIT is found to be a novel inhibitory immune checkpoint that is present on activated T cells and natural killer cells in NSCLC, among other malignancies. The prospective, phase I CITYSCAPE trial evaluated tiragolumab, known as a TIGIT antibody, in combination with atezolizumab as a frontline regimen in patients with PD-L1–positive patients who had not previously received chemotherapy. Results showed that in the intent-to-treat population, the combination showed a clinically meaningful improvement in objective response rate (ORR) and PFS versus placebo plus atezolizumab.

“Promising new immune targets always generate excitement and that is particularly true for TIGIT. The CITYSCAPE trial compared atezolizumab alone and atezolizumab with tiragolumab, an anti-TIGIT molecule, with a marked improvement in both PFS and ORR. Could the addition of an anti-TIGIT antibody lead to more immune responses and better long-term outcomes in lung cancer?”

First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS) (NCT02893332; Abstract 9508)

Researchers explored the activity of upfront stereotactic radiation plus a frontline EGFR TKI in patients with oligometastatic NSCLC in the multicenter, Chinese SINDAS trial. The use of this type of regimen demonstrated improved PFS and OS versus a TKI alone, and the data suggest that aggressive local therapy to sites at diagnosis is an approach that should continue to be explored.

“For patients with oligometastatic lung cancer, several studies have demonstrated benefit to definitive therapy in addition to systemic treatment. The SINDAS trial explored this approach in patients with EGFR-mutant NSCLC and showed that the addition of stereotactic radiotherapy to initial TKI significantly improved both PFS and OS. Critical review of the presented data will be necessary to see if this should impact current practice but the implications could be significant.”

Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA (Abstract 9501)

The immunotherapy/chemotherapy combination of nivolumab, ipilimumab, and chemotherapy versus chemotherapy alone in the frontline setting of patients with advanced NSCLC was the focus of the CheckMate-9LA trial. Findings demonstrated an improvement in OS when compared with 4 cycles of chemotherapy alone.

Based on these data, the FDA granted a priority review designation to the regimen in this setting for patients with metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations, with an expected action date of August 6, 2020.

“CheckMate-9LA explored an approach of nivolumab, ipilimumab, and 2 cycles of chemotherapy to chemotherapy alone and showed a survival benefit. While it will be difficult to resist cross trial comparisons, particularly to the CheckMate-227 long-term data also being presented, this regimen could provide both short- and long-term benefit and may emerge as a competing standard.”

HEMATOLOGIC CANCERS

Michael Thompson, MD, PhD

Michael Thompson, MD, PhD, co-director, Oncology Precision Medicine, Aurora Health Care

Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19; Abstract LBA110)

The COVID-19 and Cancer Consortium is designed for healthcare professionals to report patients whom they are treating for cancer and have also tested positive for COVID-19, in an effort to collect data and distribute information about this specific patient population. In April 2020, the multicenter effort gained international members—making it a worldwide collaboration.Early data from the registry are being presented as part of a late-breaking abstract.

“The COVID-19 and Cancer Consortium (#CCC19, ccc19.org, @COVID19nCCC) is a crowdsourced online platform developed for the rapid generation of information about patients with cancer that are positive for SARS-CoV-2. Early data on this project will be shared at a Clinical Science Symposium on “Cancer Care in the Time of COVID: Assessing Impact and Future Directions.”

Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial (Abstract LBA3)

Bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone has been a frontline standard of care in patients with newly diagnosed multiple myeloma, but in the ENDURANCE study, the go-to regimen is compared with carfilzomib (Kyprolis) plus lenalidomide/dexamethasone. Full findings will be presented from this study, which is also being presented in late-breaking form.

“The ECOG-ACRIN E1A11 phase 3 randomized clinical trial will show the results of 2 common triplet induction regiments in multiple myeloma. This will help systematically evaluate for efficacy and toxicity and inform clinical practice. There is also a second randomization with a maintenance question that is part of the study.”

Multiple myeloma (MM) vaccination (influenza, FV and pneumococcal, PV) rates worldwide and impact on infection, hospitalization, and death (Abstract 8528)

The INSIGHT MM study was designed to better understand patient and disease characteristics in multiple myeloma both at diagnosis and at relapse, as well as treatment patterns, clinical outcomes, and treatment-associated tolerability, effectiveness, quality of life, and healthcare resource utilization. The study enrolled 4318 patients from 15 countries, who are being followed-up prospectively for at least 5 yrs.

“Multiple myeloma is a cancer of the immune system. Infections are common reasons for hospitalization and death in myeloma. Vaccination in [patients with myeloma] is underutilized, based on a study of vaccination patterns in a large health system and data collected via a patient self-report online portal.

We analyzed FV and PV patterns and associated outcomes in INSIGHT MM, the largest global, prospective, observational study in myeloma to date. Global vaccination rates were low and varied by region. The US reported the highest vaccination rates and the lowest rate of deaths due to infections. Conversely, Asia had the lowest FV and PV rates and the highest incidence of deaths due to infections. Vaccination status, for both FV and PV, was an independent prognostic factor for OS on multivariate analysis. In a post–COVID-19 world, the role of infections in cancer will become increasingly important.”

HealthTree Patient Portal mediated myeloma patient-reported vaccination and antibiotic use (Abstract e20567)

HealthTree is an online portal for patients with multiple myeloma to find optimal treatment options and help identify a cure; the platform also serves as a database for the research community. It is said to be the largest single database of patients with myeloma.

“Infection is a major cause of morbidity and mortality in multiple myeloma. Vaccines are the first line of prevention for infectious diseases. Anti-microbial prophylaxis may improve patient outcomes, but real-world use has not been well characterized. HealthTree (www.healthtree.org) was created by Jenny Ahlstrom, [a myeloma patient].

We used its patient online portal to engage the patient community regarding vaccination and antimicrobial prophylaxis. [A total] 4944 patients offered the survey and 458 participated, revealing important information about this aspect of infectious disease supportive care in myeloma. This patient level data entry can complement clinical trials and institutional or other databases looking at infectious disease practice patterns.”

DREAMM-6: Safety and tolerability of belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/refractory multiple myeloma (RRMM; Abstract 8502)

The ongoing, 2-part, 2-arm DREAMM-6 (NCT03544281) trial is investigating the safety, tolerability, and clinical activity of the antibody-drug conjugate (ADC) belantamab mafodotin in combination with bortezomib/dexamethasone and lenalidomide/dexamethasone in patients with relapsed/refractory myeloma previously treated with at least 1 prior line of therapy. Early data from part 1 of the trial looking at the ADC added to bortezomib/dexamethasone show a tolerable safety profile. 

“There are 4 abstracts about the anti-BCMA antibody-drug conjugate (ADC) belantamab mafodotin (GSK2857916) and 2 trials in progress abstracts (DREAMM-5 [Abstract TPS8552] and DREAMM-9 [Abstract TPS8556]) in the “DREAMM” series of clinical trials.

[DREAMM-6] evaluates the common [bortezomib/dexamethasone] backbone with the addition of this ADC. No dose-limiting toxicities were observed. The known ocular and cytopenia safety profile was deemed acceptable with no new safety signals identified. This, in addition to the other abstracts and ongoing trials, should give us data about a new drug we will likely have available in the clinic soon.”

GASTROINTESTINAL CANCERS

Tanios S. Bekaii-Saab, MD, FACP

Tanios S. Bekaii-Saab, MD, FACP, medical oncologist; medical director, Cancer Clinical Research Office; vice chair and section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic

SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mFOLFIRINOX versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA; Abstract 4504)

The prospective, phase II SWOG S1505 trial evaluated perioperative mFOLFIRINOX versus gemcitabine/nab-paclitaxel (Abraxane) in patients with resectable pancreatic ductal adenocarcinoma (PDAC), a patient population that typically has suboptimal outcomes after curative treatment. While the findings have been eagerly awaited, data showed that neither regimen particularly improved OS over the other.

“The highly anticipated results of SWOG 1505 have been eagerly awaited. In this study, patients with clearly resectable PDAC were randomized to receive perioperative mFOLFIRINOX or gemcitabine/nab-paclitaxel with a primary outcome of 2-year OS. This study confirmed no difference in outcome between the 2 arms.

This is a very important finding since the 2 regimens have never been compared head to head in any stage of the disease, and assumptions were made that more is better without comparative data. Additionally, this study exemplified the many challenges our patients with PDAC encounter with toxicities and with the fact that less than half of patients enrolled were able to complete all planned therapy, thus suggesting examining the role of modified regimens, such as bi-weekly gemcitabine/nab-paclitaxel in this setting. Surprising and perhaps disappointing were the findings that the median OS in both arms underperformed historical controls, including single-agent gemcitabine control arms (~30 months).

One should also note that another smaller study [ESPAC 5F (Abstract 4505)] focusing on borderline resectable PDAC confirmed no difference between the gemcitabine/capecitabine doublet versus FOLFIRINOX.

The cumulative findings from both studies are welcome, since this allows our patients more options in the perioperative setting. The key message is that ‘more is not necessarily better,’ but ‘smarter is better.’ Investigators at Mayo [Clinic; Mark J. Truty, MD] and ALLIANCE [Eugene Koay, MD, PhD, of The University of Texas MD Anderson Cancer Center] are helping establish strategies to better pick the right perioperative therapy for the right patient.”

Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC; Abstract 4508)

In this phase 2 study, the combination of durvalumab (Imfinzi) and tremelimumab versus durvalumab or tremelimumab alone was evaluated in patients with advanced hepatocellular carcinoma(HCC); the population comprised of patients who did not previously receive immunotherapy and either progressed on, were intolerant to, or refused sorafenib (Nexavar). Results showed that the combination had clinical activity and a tolerable safety profile, but it is unclear what activity will be highlighted in the phase 3 HIMALAYA study (NCT03298451).

“The combination of immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 remains of questionable benefit until we see the results from randomized controlled trials. The recent conditional approval by the FDA of a combination of ipilimumab and nivolumab from a single-arm study (CheckMate-040) is awaiting the completion of the randomized first-line study CheckMate-9DW, to confirm benefit before clinical utility is determined. The results from this study are modest at best and suggest mixed findings for the combination of durvalumab and tremelimumab, pending the final results from HIMALAYA in the first-line setting versus sorafenib. The toxicities of the immune checkpoint inhibitor combinations continue to suggest toxicities that can be very limiting to wider clinical adoption.

Even if the dual immune checkpoint inhibitors approach is confirmed beneficial at the completion of ongoing phase 3 studies, it will unlikely lead to a change in our evolving standard with the newly published results of the combination of atezolizumab and bevacizumab (Avastin) that has now moved solidly into the first-line setting. The biggest challenges ahead will likely need to focus on therapeutic strategies in the refractory setting following failure of atezolizumab/bevacizumab.”

Trastuzumab with trimodality treatment for esophageal adenocarcinoma with HER2 overexpression: NRG Oncology/RTOG 1010 (Abstract 4500)

Investigators sought to determine whether trastuzumab increases DFS when combined with trimodality treatment (CRT) for patients with HER2-overexpressing esophageal adenocarcinoma. However, the addition of this approach did not improve DFS in this patient population.

“RTOG 1010 is a randomized phase 3 study that assessed the role of adding trastuzumab to CRT for HER2-expressing esophageal adenocarcinoma. Patients who were randomized to the trastuzumab/CRT arm additionally received trastuzumab for 13 cycles postoperatively. The primary end point of this study was median DFS, and the study failed to show an improvement, although a trend was observed favoring the trastuzumab arm.

However, this trend may be riddled with bias since this was an open-label study, and importantly median OS was no different between both arms. These results are disappointing but important, as they emphasize the lack of benefit for trastuzumab added to CRT in patients with resectable HER2-expressing esophageal cancer.”

Overall survival (OS) and long-term disease-free survival (DFS) of three versus six months of adjuvant (adj) oxaliplatin and fluoropyrimidine-based therapy for patients (pts) with stage III colon cancer (CC): Final results from the IDEA (International Duration Evaluation of Adj chemotherapy) collaboration (Abstract 4004)

Previously, in the overall population of the IDEA pooled analysis, non-inferiority was not demonstrated in 3-year DFS outcomes in patients with stage III colon cancer who were receiving either 3 months or 6 months of adjuvant FOLFOX/CAPOX. With the 5-year follow-up, results showed that the OS rates were higher than historical rates, regardless of the duration of treatment.

“The IDEA collaboration study showed in the first pooled analysis of its primary end point for DFS, that CAPOX (but not FOLFOX) for 3 months was as effective as 6 months in the adjuvant treatment of patients with stage 3 colon cancer. Importantly, there were less toxicities, and more specifically significantly less lifelong debilitating neuropathy in the 3 months–treated arm. In this abstract, the IDEA authors present the eagerly awaited 5-year survival rate for 3 versus 6 months duration of therapy.

The authors put special (and correct) emphasis on the clinical context of their findings, which unmitigatedly support the use of 3 months of adjuvant CAPOX as the standard for the vast majority of stage III colon cancer, and arguably from last year’s update for high-risk stage II (T4N0). These findings need to be widely and consistently adopted worldwide, given their clinical meaningfulness.

Additionally, and given that fluoropyrimidines are the primary driver of benefit in the adjuvant treatment of colon cancer, I would strongly advocate against any use of oxaliplatin beyond 3 months. In a shared decision model, if exceptionally a decision to proceed with 3 additional months of therapy—such as FOLFOX use or personal preference—one should consider single-agent capecitabine for the rest of the course.”

A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with hepatectomy alone for liver metastasis from colorectal cancer: JCOG0603 study (Abstract 4005)

Patients with liver-only metastases from colorectal cancer are said to have an unclear outcome from adjuvant chemotherapy following hepatectomy. In the phase 2/3 trial, researchers compared the use of adjuvant mFOLFOX6 versus hepatectomy alone. However, results showed that the addition of mFOLFOX6 improved DFS, but this did not correlate with OS, suggesting the added treatment is not beneficial.

“The role of perioperative therapy for clearly resectable liver-only metastases (LM) from colorectal cancer (CRC) remains a subject of debate. [Results from] EORTC 40983 (EPOC) suggested a modest DFS benefit from administration of perioperative FOLFOX versus no therapy, with no meaningful change in 5-year rate of OS.

The new EPOC study assessed the role of cetuximab (Erbitux) plus FOLFOX versus FOLFOX in the perioperative setting, and found a concerning detrimental effect from the addition of cetuximab to FOLFOX. The authors of this abstract present their findings of JCOG0603, a randomized, phase 3 study comparing the efficacy of postoperative mFOLFOX following resection of LM in CRC versus resection only. The study suggested a trend for DFS benefit, but a detriment for OS. Therefore, the authors correctly conclude that postoperative FOLFOX should not be administered in patients who undergo resection for LM in CRC.

How [do we] interpret this very confusing set of data coming from 3 different randomized trials over the last 10 years? It is reasonable to recommend that the best standard for patients with clearly resectable LM in CRC is surgery only. The role of perioperative or postoperative treatment with FOLFOX at best may improve DFS but not OS, with a potential detriment to OS —especially with the addition of cetuximab.

How do we make sense of all this? LM in CRC is a complex problem and may be dichotomous in the sense that perhaps about 30% of LM in CRC recurrences are local. In this setting, systemic therapy will not add much benefit.

On the other hand, if LM in CRC is a first manifestation of more systemic disease, then surgery will not be curative; systemic therapy will perhaps prolong DFS, but will not affect OS. In a value-based system, this will not pass the ‘muster test.’ Future research could assess in a prospective and randomized fashion the role of circulating tumor DNA as a measure of minimal residual disease, and a potential predictor for the value of postoperative therapy.”