Welcome Back to McCormick: Highlights from the 2022 American Society of Clinical Oncology Annual Meeting

GI/Heme Medical Science Liaison
Daiichi Sankyo, Inc
Warwick, RI

For the first time in over two years, ASCO welcomed in person attendees back to McCormick Place in Chicago for its annual meeting. This is the largest oncology conference of the year and the energy in the building was palpable. You could tell that everyone was excited to be back in person together pushing the field of oncology forward. It was only fitting that this year’s theme was “Advancing Equitable Cancer Care Through Innovation”.

The last time a presentation received a standing ovation at ASCO was 20 years ago. On Sunday, June 5th, Dr. Shanu Modi received just that. It was an incredibly humbling experience to be present for the standing ovation in the audience during the plenary session and that is where we will start.

DESTINY-Breast04, presented by Dr. Shanu Modi from Memorial Sloan Kettering Cancer Center, was a phase III, randomized trial (2:1) comparing Trastuzumab Deruxtecan and physician’s choice of chemotherapy in patients with metastatic breast cancer who had received 1-2 lines of therapy in the metastatic setting that was HER2-low, meaning that the tumor had HER2 expression by immunohistochemistry (IHC) that was 1+ or 2+ with a negative in situ hybridization (ISH).1 The primary end point was progression free survival by blinded independent central review in those patients that were hormone receptor positive (HR+). Secondary endpoints included progression free survival (PFS) by blinded independent central review in all patients and overall survival (OS) in HR+ and all patients. Exploratory endpoints included PFS and OS in HR- patients. Treatment with physician’s choice chemotherapy included eribulin, capecitabine, nab-paclitaxel, gemcitabine, and paclitaxel. The study met its primary endpoint with median PFS in the HR+ patients being 10.1 months in the Trastuzumab Deruxtecan arm compared to 5.4 months in the physician’s choice arm (HR=0.51, 95% CI 0.40-0.64, p<0.0001). Additionally, all secondary endpoints were met. PFS in all patients was 9.9 months in the Trastuzumab Deruxtecan arm compared to 5.1 months in the physician’s choice arm (HR=0.50, 95% CI 0.40-0.63, p<0.0001). OS in the Trastuzumab Deruxtecan HR+ and all patients arms were 23.9 and 23.4 months, respectively, compared to 17.5 and 16.8 months in the physician’s choice arm (HR=0.64, 95% CI 0.48-0.86, P<0.0028 and HR 0.64, 95% CI 0.49-0.84, P=0.0010). In HR- patients PFS & OS were 8.5 and 18.2 months compared to 2.9 and 8.3 months in the physician’s choice arm (PFS HR=0.46, 95% CI 0.24-0.89 & OS HR=0.48, 95% CI 0.24-0.95). The most common all grade adverse events occurring in >20% of patients in the Trastuzumab Deruxtecan arm were nausea (73%), fatigue (48%), alopecia (38%), vomiting (34%), neutropenia (33%), anemia (33%), thrombocytopenia (24%), and diarrhea (22%). Adverse events of significant interest with Trastuzumab Deruxtecan included drug-related interstitial lung disease and pneumonitis (all grade ILD = 12.1%) and left ventricular dysfunction (all grade = 4.3%). According to several physicians who were in the audience, this trial has the potential to change how we think about HER2.

PARADIGM, presented by Dr. Takayuki Yoshino from National Cancer Center East, was a phase III randomized (1:1) trial comparing mFOLFOX + Panitumumab vs mFOLFOX + Bevacizumab in patients with previously untreated RAS wild type (wt) metastatic colorectal cancer.2 The primary endpoint was OS in left-sided (and if positive, the entire population) metastatic colorectal cancer. Secondary endpoints included PFS, response rate (RR), duration of response (DOR), rate of R0 resection, and safety in the left sided and overall populations. mFOLFOX + Panitumumab showed superiority in OS compared to mFOLFOX + Bevacizumab (37.9 months vs 34.3 months, HR=0.82, 95.798 % CI = 0.68-0.99; P=0.031) in a left sided patient population. In the overall population, mFOLFOX + Panitumumab had a median OS of 36.2 months vs 31.3 months in the mFOLFOX + Bevacizumab arm (HR=0.84, 95% CI 0.72-0.98; P=0.030). PFS in the left sided and overall population was not statistically significantly different between the two arms. Response rate was numerically higher in the panitumumab arm in the left sided (80.2% vs 68.6%) and overall populations (74.9% & 67.3). The most common adverse events (>20% all grade) in the panitumumab arm compared to the bevacizumab arm were acne-like dermatitis, stomatitis, paronychia, dry skin, and hypomagnesemia. The results of this trial help to clarify EGFR vs VEGF in a frontline mCRC setting.

rEECur, presented by Dr. Martin McCabe from the University of Manchester/Royal Manchester Children’s Hospital, was a unique and adaptive trial in patients with recurrent and primary refractory Ewing Sarcoma.3 It was a phase II/III, multi-arm, multistage randomized trial that was designed to drop arms that were not as effective. The four arms that were tested in phase II were Gemcitabine/Docetaxel (GD), Irinotecan/Temozolamide (IT), Topotecan/Cyclophosphamide (TC), and high-dose Ifosfamide (I). The regimens that made it to phase III were TC and I. The primary outcome was event free survival (EFS). Secondary outcomes included PFS, OS, quality of life (QOL) and safety. Median EFS was 5.7 months in the Ifosfamide arm compared to 3.5 months in the Topotecan/Cyclophosphamide arm. Median OS was 15.4 vs 10.5 months in the Ifosfamide vs Topotecan/Cyclophosphamide arm. Adverse events were greater in the Ifosfamide arm, including a higher rate of grade 3/4 encephalopathy (7% vs. 0%) and nephrotoxicity (8% vs. 0%).

DETERMINATION, presented by Dr. Paul Richardson from Dana Farber Cancer Institute, was a phase III, randomized (1:1) trial looking at Lenalidomide, Bortezomib, and Dexamethasone (RVd) with or without early autologous stem cell transplant (ASCT) followed by lenalidomide (R) maintenance in newly diagnosed multiple myeloma patients. The primary endpoint was PFS and secondary endpoints included RR, DOR, time to progression, OS and QOL/safety. This study met its primary endpoint, as median PFS was 67.5 months in the RVd+ASCT arm versus 46.2 months in the RVd arm (HR=1.53, 95% CI 1.23-1.91, p<0.0001). OS was similar between the two arms. In those patients who received RVd+ASCT, grade 3 or greater adverse events were significantly higher than in those patients who did not receive ASCT. Secondary malignancies, particularly AML/MDS, were higher in the RVd+ASCT arm.

TROPiCS-02, presented by Dr. Hope Rugo from the UCSF Carol Franc Buck Breast Care Center, was a phase III, randomized (1:1) trial of Sacituzumab Govitecan (SG), a TROP-2 targeted antibody drug conjugate, versus treatment of physician’s choice (TPC) of capecitabine, vinorelbine, gemcitabine, or eribulin in patients with hormone receptor-positive/HER2-negative advanced breast cancer who had received prior hormonal therapy, a taxane, and a CDK4/6 inhibitor in any setting and 2-4 lines of prior therapy for metastatic disease.5 The primary endpoint for this trial was PFS by blinded independent central review. Secondary endpoints include OS, objective response rate, clinical benefit rate, DOR, patient reported outcomes, and safety. The study met its primary endpoint. Median PFS was 5.5 months in the SG arm compared to 4 months in TPC (HR=0.66 95% CI 0.53-0.83, P=0.0003). Six-, 9-, and 12-month PFS rate were numerically higher in the SG arm compared to TPC at all time points. Median OS was not different between the two groups, at 13.9 months for SG and 12.3 months for TPC. The ORR and CBR were 21% & 34% in the SG arm compared to 14% & 22% in the TPC arm. Grade 3 or greater treatment emergent adverse events were higher in the SG arm (74% vs 60%) compared to the TPC arm. The most common all grade adverse events in the SG arm were hematological (neutropenia, anemia) and gastrointestinal (diarrhea, nausea) in nature with neutropenia and diarrhea being the most common grade 3 or greater adverse events.

DoSTARlimab, PD-1 blockade as curative-intent therapy in mismatch repair deficient locally advanced rectal cancer, presented by Dr. Andrea Cercek from Memorial Sloan Kettering Cancer Center, was a phase II trial of neoadjuvant Dostarlimab administered for 6 months to stage II & III mismatch repair deficient rectal cancer.6 The primary objectives for this study was ORR and pathologic complete response or clinical complete response rate at 12 months. Secondary endpoints included safety and tolerability. ORR was 100% in the first 14 consecutive patients with the responses being a clinical complete response with a durable duration of response. Each of these 14 patients have not required chemotherapy, radiation or surgery and no disease recurrence has been reported during follow up. Dostarlimab was well tolerated with no > grade3 adverse events reported. This trial garnered a lot of media buzz given the 100% clinical complete response rate and was reported by all the major news outlets; however, the results should be interpreted with caution given the small sample size, short follow up, and phase II study design. 

Besides the clinical data that were presented, there was also a focus on diversity, equity, and inclusion (DEI) in all aspects of healthcare. One example of this was, Dr. Narjust Duma, from the Dana Farber Cancer Institute, who lead us through better understanding bias and microaggressions. Dr. Cardinale Smith, from Mount Sinai, described racial and ethnic disparities in end-of-life care. It was inspiring to see the work being done in DEI and all of us have the responsibility as healthcare providers to ensure that the future of oncology is bright, diverse, inclusive, and equitable.

Save the Date: ASCO’s 2023 meeting will be held in Chicago on June 2-6; More information is available on their website: www.asco.org

References

1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. J Clin Oncol. 2022;40(suppl; abstr LBA3).
2. Yoshino T, Watanabe J, Shitara K, et al. Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial. J Clin Oncol. 2022;40(suppl; abstr LBA1).
3. McCabe M, Kirton L, Khan M, et al. Phase III assessment of topotecan and cyclophosphamide and high-dose ifosfamide in rEECur: An international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). J Clin Oncol. 2022;40(suppl; abstr LBA2).
4. Richardson PG, Jacobus SJ, Weller E, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) +/- autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): The phase 3 DETERMINATION trial. J Clin Oncol.  2022;40(suppl; abstr LBA4).
5. Rugo HS, Bardia A, Marme F, et al. Primary results from TROPiCS-02: A randomized phase 3 study of Sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer. J Clin Oncol. 2022;40(suppl; abstr LBA1001).
6. Cercek A, Lumish MA, Sinopoli JC, et al. Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer. J Clin Oncol. 2022;40(suppl; abstr LBA5).