An Expert’s Guide to ASCO 2022: Preview of the Top Abstracts

During the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, important results from many clinical trials in both solid tumors and hematologic malignancies will be reported. Below, oncology experts have highlighted their most anticipated abstracts, which we will cover online as a part of CCO’s Independent Conference Coverage of ASCO 2022. Remember to check the CCO website often as the meeting unfolds for downloadable slidesets summarizing the data from these studies and more, as well as after the meeting for CME-certified online activities featuring expert analyses and perspectives on the clinical implications of the new data.

Top Picks: Breast Cancer and Gynecologic Cancers
At ASCO 2022, several studies in breast cancer and gynecologic cancers are being presented as late-breaking abstracts. Many other interesting studies also are being reported.

In breast cancer, Joyce O'Shaughnessy, MD, identified the following as her top abstracts to watch.

• DESTINY-Breast04: phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice in HER2-low metastatic breast cancer (MBC) (abstract LBA3); results from this trial identify a new subtype of MBC—HER2 low—and report improved progression-free survival (PFS) and overall survival (OS) with T-DXd vs standard therapy in this patient population
• TROPiCS-02: phase III study of sacituzumab govitecan vs treatment of physician’s choice in hormone receptor (HR)-positive, HER2-negative advanced breast cancer (abstract LBA1001); reports of positive primary endpoint of improvement in PFS for this study suggest that sacituzumab govitecan may become another treatment option for patients with HR-positive, HER2-negative MBC
• MAINTAIN: phase II study of fulvestrant or exemestane ± ribociclib after disease progression on estrogen receptor (ER) therapy with a CDK4/6 inhibitor in HR-positive, HER2-negative MBC (abstract LBA1004); whether this trial supports use of CDK4/6 inhibitors at the time of switching endocrine therapy after progression on previous treatment with an aromatase inhibitor and a CDK4/6 inhibitor will strongly influence patient management

In gynecologic cancers, Angeles Alvarez Secord, MD, MHSc, selected the following highly anticipated studies at the meeting.

• ATHENA-MONO (GOG-3020/ENGET-ov45): phase III trial of rucaparib vs placebo as maintenance after response to frontline platinum-based chemotherapy in patients with newly diagnosed ovarian, fallopian tube, or peritoneal cancer (abstract LBA5500)
• Randomized, open-label, 3-arm phase II trial of the selective glucocorticoid receptor modulator relacorilant + nab-paclitaxel vs chemotherapy in patients with recurrent, platinum-resistant ovarian cancer—OS results (abstract LBA5503)
• MITO23: randomized phase III trial on trabectedin (ET-743) vs physician’s choice chemotherapy for recurrent primary peritoneal, fallopian tube, or ovarian cancer with BRCA mutation or BRCAness phenotype (abstract LBA5504)
• innovaTV 205/ENGOT Cx8/GOG 3024: interim results from a phase I/II study of tisotumab vedotin + pembrolizumab as frontline treatment for recurrent or metastatic cervical cancer (abstract 5507); reports encouraging, durable antitumor activity with a manageable safety profile in this setting

Additional studies to watch in breast cancer and gynecologic cancers include:

• LUMINA: prospective trial to assess omitting radiotherapy following breast-conserving surgery for T1N0, luminal A breast cancer (abstract LBA501)
• PALOMA-2: OS results with palbociclib + letrozole vs placebo + letrozole for ER-positive, HER2-negative advanced breast cancer (abstract LBA1003)
• FAKTION: OS and updated PFS results from phase II study of capivasertib + fulvestrant vs placebo + fulvestrant after relapse or progression on an aromatase inhibitor in ER-positive advanced breast cancer (abstract 1005)
• KEYNOTE-826 (subgroup analysis): pembrolizumab + chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer (abstract 5506)
• ORZORA: multicenter, open-label phase IV study of olaparib maintenance in platinum-sensitive relapsed ovarian cancer (abstract 5519)
• GARNET: phase I study of dostarlimab in mismatch repair deficient (dMMR)/microsatellite instability–high (MSI-H) or mismatch repair proficient/microsatellite stable endometrial cancer (abstract 5509)

Top Picks: Hematologic Malignancies
Several interesting and potentially practice-changing studies in hematologic malignancies are being reported at ASCO 2022.

In multiple myeloma (MM), Shaji K. Kumar, MD, identified the following abstracts to watch.

• DETERMINATION: phase III trial of lenalidomide/bortezomib/dexamethasone ± autologous stem cell transplant (ASCT) followed by lenalidomide maintenance for newly diagnosed MM (abstract LBA4)
• ATLAS: phase III study of carfilzomib/lenalidomide/dexamethasone (KRd) vs lenalidomide maintenance after ASCT for newly diagnosed MM (abstract 8001); reports improved PFS with extended, measurable residual disease (MRD) response–adapted KRd therapy vs lenalidomide maintenance after induction and ASCT
• MajesTEC-1: phase I/II study of the BCMA bispecific antibody teclistamab in relapsed/refractory (R/R) MM (abstract 8007); updated efficacy and safety continue to show deep and durable responses, even in heavily pretreated patients with R/R MM

In lymphomas, John M. Burke, MD, identified the following abstracts to watch.

• ECHELON-1: phase III study of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine in untreated stage III/IV classical Hodgkin lymphoma (abstract 7503); A+AVD continues to show improved OS after approximately 6 years, making it the standard therapy for frontline treatment of advanced-stage Hodgkin lymphoma
• SHINE: phase III study of ibrutinib with bendamustine + rituximab (BR) and rituximab maintenance in older patients with mantle cell lymphoma (MCL) (abstract LBA7502)
• Glofitamab: pivotal phase II study of the CD20XCD3 bispecific antibody glofitamab in R/R diffuse large B-cell lymphoma (DLBCL) (abstract 7500); an overall response rate (ORR) of 50% was observed in the expansion cohort of patients with R/R DLBCL and ≥2 prior therapies, but whether these results will lead to an accelerated FDA approval remains to be seen
• CAPTIVATE: 3-year follow-up of phase II study of ibrutinib + venetoclax in first-line chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (abstract 7519); results from this trial of fixed duration therapy continue to show durable responses, even in high-risk patients, with an unchanged safety profile

In leukemias, Eunice S. Wang, MD, identified the following abstracts of interest.

• Pre-MEASURE: multicenter evaluation of the prognostic significance of MRD testing prior to allogeneic stem cell transplant (SCT) for adult patients with acute myeloid leukemia (AML) in first remission (abstract 7006); study of a large multicenter cohort (N = 448) of patients with AML in first complete remission found MRD status prior to allogenic SCT prognostic for risk of relapse post SCT
• IDHENTIFY: OS byIDH2-mutant allele (R140 or R172) in patients with late-stage mutated IDH2 relapsed or refractory AML receiving enasidenib or conventional care regimens in this phase III trial (abstract 7005); study of patients with R/R AML and the IDH2 mutation found that mutational burden and comutational profiles differed between patients with IDH2-R140 and IDH2-R172 and that enasidenib significantly improved survival outcomes for patients with IDH2-R172 mutations
• Long-term results of a phase II trial of crenolanib combined with 7+3 chemotherapy in adults with newly diagnosed FLT3-mutant AML (abstract 7007); long-term outcomes in patients with newly diagnosed FLT3-mutant AML of the FLT3 inhibitor crenolanib combined with 7+3 induction and consolidation demonstrate high response rates and median OS not reached at a median follow-up of 45 months

Additional studies to watch in hematologic malignancies include:

• Updates from first-in-human study of the BCMA/CD19 dual-targeting fast CAR T-cell therapy GC012F in R/R MM (abstract 8005)
• Rosewood: phase II study of zanubrutinib + obinutuzumab vs obinutuzumab in patients with R/R follicular lymphoma who previously received ≥2 lines of therapy (abstract 7510)
• Phase II study of ibrutinib, obinutuzumab, and venetoclax in patients with treatment-naive or R/R CLL (abstract 7540)
• Zilovertamab: phase I/II study of zilovertamab, a humanized antibody to ROR1, with ibrutinib in MCL or CLL (abstract 7520)
• ASCEND: phase III trial of acalabrutinib vs idelalisib + rituximab vs bendamustine + rituximab in R/R CLL (abstract 7538); after approximately 4 years of follow-up, acalabrutinib maintained prolonged PFS compared with the rituximab-based regimens
• ELEVATE-TN: phase III trial of acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil as first-line therapy in CLL (abstract 7539); at 5 years of follow-up, ORR and median OS were longer with acalabrutinib + obinutuzumab compared with obinutuzumab + chlorambucil
• Phase I/II trial of favezelimab, a LAG-3 inhibitor, in combination with pembrolizumab in patients with R/R classical Hodgkin lymphoma without prior anti–PD-1 therapy (abstract 7516)
• Phase I/II trial of favezelimab, a LAG-3 inhibitor, in combination with pembrolizumab in patients with R/R classical Hodgkin lymphoma refractory to anti–PD-1 therapy (abstract 7545)
• Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53-mutant AML: phase Ib results (abstract 7020)
• Phase II trial of a chemotherapy-free combination of ponatinib and blinatumomab in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) (abstract 7009)
• Updated results from a phase II study of mini–hyper-CVD + inotuzumab ozogamicin ± blinatumomab in older adults with newly diagnosed Philadelphia chromosome–negative B-cell ALL (abstract 7011)
• Efficacy and safety results from ASCEMBL, a phase III study of asciminib vs bosutinib in patients with chronic myeloid leukemia in chronic phase after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update (abstract 7004)

Top Picks: Lung Cancer
Stephen Liu, MD, and Zofia Piotrowska, MD, MHS, have identified several key studies in lung cancer of interest at ASCO 2022.

• Association analysis of pathological regression and event-free survival in the phase III CheckMate 816 study evaluating neoadjuvant nivolumab + chemotherapy vs chemotherapy alone for resectable (stage IB-IIIA) non-small-cell lung cancer (NSCLC) (abstract LBA8511); neoadjuvant chemo-immunotherapy has generated great interest based on its benefit in patients who achieve a pathologic complete response, but what are the outcomes for those who achieve a major pathologic response (not complete) vs those who do not?
• CHRYSALIS-2: updated results of amivantamab + lazertinib in patients with EGFR-mutated advanced NSCLC post osimertinib and platinum-doublet chemotherapy (abstract 9006); reports updated efficacy of adding the EGFR-MET bispecific antibody amivantamab to EGFR TKI therapy upon disease progression, portending the availability of an important treatment option in a setting where there are no approved targeted therapies
• KRYSTAL-1: efficacy and safety of the KRAS G12C inhibitor adagrasib (MRTX849) in patients with KRAS G12C–mutated advanced/metastatic NSCLC from cohort A, a phase II cohort with registrational intent (abstract 9002); adagrasib has FDA breakthrough therapy designation in this setting, with this report providing an important update on its safety and efficacy profile in its preapproval state; it is anticipated that adagrasib will soon join the KRAS G12C inhibitor sotorasib as an FDA-approved option for these patients
• KRYSTAL-1: evaluation of adagrasib in patients with KRAS G12C–mutated NSCLC and active, untreated central nervous system (CNS) metastases (abstract LBA9009); CNS active treatments for patients with advanced/metastatic NSCLC continue to be an important unmet need in the clinic, with this report providing much-needed information about the CNS activity of adagrasib

Additional studies to watch in lung cancer include:

• Efficacy and safety of patritumab deruxtecan (HER3-DXd) in advanced/metastatic NSCLC without EGFR-activating mutations after platinum-doublet chemotherapy ± immunotherapy, from an ongoing phase I study (abstract 9017)
• ATEZO-BRAIN trial: updated analysis of atezolizumab + carboplatin and pemetrexed in patients with advanced NSCLC with untreated brain metastases (abstract 9010) 
• A phase I/IIA trial of  CLN-081 in patients with EGFR exon 20 insertion–positive NSCLC (abstract 9007)
• TACTI-002: updated results from a phase II trial of the soluble LAG-3 protein eftilagimod alpha and pembrolizumab as first-line treatment in a PD-L1–unselected population of patients with metastatic NSCLC (abstract 9003)
• OPAL (NEJ032C/LOGIK1801): phase II study of osimertinib in combination with platinum + pemetrexed in patients with EGFR-mutated advanced NSCLC (abstract 9097)
• ATLANTIS: phase III study of single-agent lurbinectedin as treatment for patients with relapsed small-cell lung cancer (abstract 8524)

Top Picks: Skin Cancer
Hussein Tawbi, MD, PhD, and Allison Betof Warner, MD, PhD, have identified several key studies in skin cancer of interest at ASCO 2022.

• PRADO: phase II study of personalized therapy post neoadjuvant nivolumab + ipilimumab in stage III melanoma (abstract 9501); updated results for recurrence-free survival rate and distant metastasis–free survival rate for patients with major pathologic response who did not undergo therapeutic lymph node dissection suggest that this subgroup of patients could safely be spared from therapeutic node dissection
• RELATIVITY-047: OS and ORR by subgroup with relatlimab + nivolumab vs nivolumab in previously untreated advanced/metastatic melanoma (abstract 9505); the combination of relatlimab + nivolumab demonstrated superior PFS and ORR in the frontline setting vs nivolumab in this phase II/III trial, which led to recent approval by the FDA for this combination; this update reports additional efficacy and safety data with the combination, showing a benefit across several key subgroups and no new safety signals
• Phase Ib study: updated OS data in metastatic cutaneous melanoma with tebentafusp± durvalumab and/or tremelimumab (abstract 104); tebentafusp is the first agent to show a survival benefit for metastatic uveal melanoma, so there has been great enthusiasm for this agent; this report on OS data on tebentafusp + durvalumab ± tremelimumab for patients with heavily pretreated metastatic cutaneous melanoma is promising, warranting further investigation of this combination for the treatment of immune checkpoint–refractory cutaneous melanoma
• TRICOTEL: phase II study of triplet therapy with atezolizumab + vemurafenib + cobimetinib in BRAF-mutated metastatic melanoma and active brain metastases (abstract 9515); primary results on ORR, PFS, and intracranial outcomes show good efficacy, especially in patients with symptomatic disease or those receiving steroids; this positive outcome in one of the highest-risk populations for which we do not have any good therapies is likely to affect how we treat those patients in the future 
• AMBER: cobolimab + dostarlimab for advanced or metastatic melanoma (abstract 9513); reports safety and efficacy of the anti-TIM3 antibody cobolimab in combination with an anti–PD-1 antibody; response rates similar to nivolumab + relatlimab as first-line therapy, thus TIM3 could be a fourth checkpoint where blockade could be therapeutically relevant, and this is likely to lead to larger randomized phase II or III studies with this combination

Additional studies to watch in skin cancer include:

• KEYNOTE-716: distant metastasis–free survival with adjuvant pembrolizumab vs placebo in stage IIB/C melanoma (abstract LBA9500)
• SWOG 1512: neoadjuvant pembrolizumab for desmoplastic melanoma (abstract 9502)
• NeoTrio: neoadjuvant pembrolizumab with dabrafenib + trametinib either concurrently or in sequence in BRAF-mutant stage III melanoma (abstract 9503)
• Phase II trial: first-line therapy for acral melanoma with camrelizumab + apatinib and temozolomide (abstract 9508)

Top Picks: Gastrointestinal Cancers
Christopher H. Lieu, MD, and Rachna Shroff, MD, MHS, have identified several key studies of interest in GI cancers at ASCO 2022.

• PARADIGM: phase III trial of first-line panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6 for patients with RAS wild-type metastatic colorectal cancer (CRC) (abstract LBA1); there is significant interest in determining whether EGFR inhibition in combination with chemotherapy is superior to VEGF inhibition + chemotherapy in RAS wild-type metastatic CRC with left-sided primary tumors
• CAIRO5: phase III trial of FOLFOXIRI + bevacizumab vs FOLFOX/FOLFIRI + bevacizumab in patients with initially unresectable colorectal liver metastases and right-sided and/or RAS/BRAF V600E–mutated primary tumors (abstract LBA3506); as with the previous study, this presentation should shed light on best practices on the uses of chemotherapy and targeted therapy for patients with advanced CRC with specific features
• HERB: investigator-initiated phase II study of T-DXd for patients with HER2-expressing unresectable or recurrent biliary tract cancer (abstract 4006); this study will add to the promising data emerging with targeted therapies for patients with biliary tract cancer, with a promising response rate for HER2-positive cancers

Additional studies to watch include:

• HIMALAYA: patient-reported outcomes from the phase III study of durvalumab ± tremelimumab vs sorafenib for patients with unresectable hepatocellular carcinoma (abstract 4074)
• CheckMate 142: 5-year efficacy and safety data from the phase II study of nivolumab ± ipilimumab for patients with dMMR/MSI-H metastatic CRC (abstract 3510)
• Phase II study: PD-1 inhibitor dostarlimab as curative-intent treatment for locally advanced, dMMR rectal cancer (abstract LBA5)
• CONKO-007: randomized phase III trial of sequential induction chemotherapy followed by chemoradiotherapy vs chemotherapy alone for nonresectable locally advanced pancreatic cancer (abstract 4008)
• TRIPLETE: randomized phase III trial of first-line mFOLFOXIRI + panitumumab vs mFOLFOX6 + panitumumab for patients with unresectable metastatic RAS and BRAF wild-type CRC (abstract LBA3505)