Clarivate oncology experts analyzed more than 2,400 ASCO abstracts and selected the top 10 based on their expected impact on the drug treatment landscape. In the following article, we share our analysis of these exciting breakthroughs, data and takeaways for life sciences executives.
“Equity: Every Patient. Everyday. Everywhere”
The ASCO Annual Meeting is the biggest oncology event of the year. Due to the ongoing COVID-19 global pandemic, like last year, the meeting held virtually on June 4 – 8. The theme of this year, “Equity: Every Patient. Everyday. Everywhere.”, prioritizes areas for future research focus and emphasizes the importance of including underserved patient populations in clinical research to increase access.
As part of our Drugs to WatchTM series, which reviews therapies expected to have significant impact on drug landscapes, Clarivate oncology experts sifted through the more than 2,400 abstracts that were accepted for presentation and selected their top picks. In the following article, we present our analysis of these abstracts and key takeaways for life sciences executives.
ASCO 2021 is set to unveil plenty of news that will impact the spectrum of oncology markets. One of the most striking trends that we observed at this year’s annual meeting was the number of abstracts that report data for targeted therapies in earlier stages of disease (or adjuvant setting), including in difficult-to-treat cancers where in some cases there are no or few drug-treatment options.
For more in-depth analyses of key data emerging from the Annual Meeting, watch out for from our expert team.
1. Tecentriq shows promise as adjuvant therapy for resectable early-stage NSCLC
Tecentriq may become the first immune checkpoint inhibitor to gain approval for certain patients with resectable early-stage NSCLC based on significant DFS (disease-free survival) benefits
Context: Multiple immune checkpoint inhibitors are being evaluated as adjuvant therapies for resectable NSCLC. In March 2021, the pivotal Phase III IMpower010 trial, evaluating Roche’s Tecentriq versus best supportive care (BSC) in stage IB-IIIA NSCLC after complete resection and adjuvant chemotherapy, met its primary endpoint of DFS, becoming the first immune checkpoint inhibitor to show a meaningful clinical benefit in this setting.
What’s new from ASCO: Results show a significant improvement in DFS for Tecentriq versus BSC in stage II-IIIA patients with tumor-cell PD-L1 expression ≥ 1% (HR 0.66, P = 0.0039) and in all randomized patients with stage II-IIIA NSCLC (HR 0.79, P = 0.0205). At the time of this analysis, DFS did not cross the significance boundary in the overall intent-to-treat population (stage IB-IIIA) and overall survival data were immature.
2. Lynparza shows superiority over placebo in patients with germline BRCA1/2 mutations and high-risk HER2-negative early-stage breast cancer
Can data from OlympiA enable Lynparza to overthrow competition from existing players in the early-stage breast cancer market?
Context: In February 2021, AstraZeneca announced that Lynparza met the primary endpoint of superior invasive DFS over placebo in patients with BRCA-mutated, high-risk HER2-negative early-stage breast cancer in the Phase III OlympiA study.
What’s new from ASCO: AstraZeneca presented further data from this pivotal study. OlympiA is investigating Lynparza in the adjuvant setting where no other PARP inhibitors are being evaluated; if Lynparza secures regulatory approval in this setting, it will face stiff competition from the well-entrenched anti-PD-1/PD-L1 inhibitors, Tecentriq and Keytruda. Given the potential of the PD-1/PD-L1 agents to evoke deep and prolonged clinical responses, physicians may be inclined to prescribe immune checkpoint inhibitors over a PARP inhibitor. Moreover, OlympiA is also targeting a small patient subpopulation of BRCA1/2-mutated triple-negative breast cancer patients.
What to expect: Despite these potential setbacks, physicians have been eagerly awaiting the results of this trial because of Lynparza’s proven efficacy in HER2-negative BRCA1/2-mutated advanced breast cancer patients. If successful, the OlympiA results will likely support the label expansion of Lynparza in early-stage disease, and greatly expand Lynparza’s eligible patient pool in breast cancer.
3. Keytruda shows benefit as adjuvant therapy in renal cell carcinoma
Will Keytruda open the gates for anti-PD-1/PD-L1 therapy in the adjuvant setting of the renal cell carcinoma market?
Context: In April 2021, Merck announced that KEYNOTE-564 had met the primary endpoint of DFS over placebo, which marks the first positive result for an anti-PD-1/PD-L1 therapy in the adjuvant setting in RCC.
What’s new from ASCO: Merck presented preliminary analyses of the KEYNOTE-564 trial, assessing Keytruda as an adjuvant therapy in renal cell carcinoma patients following nephrectomy.
What to expect: Adjuvant therapy in renal cell carcinoma represents an untapped market and a potential avenue of growth for immune checkpoint inhibitors. The data will broaden Keytruda’s opportunity in renal cell carcinoma, further extending its currently approved indication in combination with Inlyta for first-line advanced renal cell carcinoma.
Keytruda’s expansion into the adjuvant setting could reshape the treatment landscape for this disease and undoubtedly provides a significant opportunity for lifecycle management in this indication.
4. Opdivo demonstrates remarkable efficacy benefit as adjuvant therapy for resected esophageal or gastroesophageal junction cancer
Armed with CheckMate-577 data, Opdivo can potentially change treatment practice for early-stage esophageal or gastroesophageal junction (GEJ) cancer
Context: In May 2021, based on DFS results from the Phase III CheckMate-577 trial, the FDA approved Opdivo as adjuvant therapy for treatment of completely resected esophageal or GEJ cancer patients with residual pathologic disease who have received neoadjuvant chemoradiotherapy.
What’s new from ASCO: Additional data from this trial exhibits the impressive difference in median distant metastasis-free survival between the adjuvant Opdivo and placebo arms (28.3 vs. 17.6 months, respectively; HR 0.74). Data show that patients’ quality of life was maintained and that Opdivo’s safety profile was manageable in the clinical setting.
What to expect: These outcomes will likely help establish Opdivo as a new standard of care in the adjuvant resected esophageal or GEJ cancer setting, where no other targeted agents are currently approved. Of note, Opdivo is also approved as adjuvant therapy for certain patients with malignant melanoma.
5. Bristol Myers Squibb set to position Opdivo combinations as first-line treatment of advanced or metastatic esophageal squamous cell carcinoma
CheckMate-648 data could enable approval of Opdivo combinations for previously untreated patients, but they will face competition from Keytruda in this segment
Context: Like in many other oncology indications, combinations therapies are being developed for esophageal cancer.
What’s new from ASCO: Bristol Myers Squibb disclosed results from the Phase III CheckMate-648 trial evaluating Opdivo plus Yervoy and Opdivo plus chemotherapy as first-line treatments for unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
What to expect: If successful, this trial will likely lead to the FDA approval of Opdivo plus Yervoy and/or Opdivo plus chemotherapy regimens, moving Opdivo to earlier lines in the treatment pathway for metastatic ESCC (where it is currently approved for use after prior fluoropyridimine- and platinum-based chemotherapy). However, given that Keytruda plus chemotherapy is already approved for locally advanced or metastatic esophageal and GEJ carcinoma ─ a broader indication than that investigated in CheckMate-648─Opdivo-based combinations will likely face fierce competition from Keytruda.
6. Keytruda plus Herceptin and chemotherapy brings new treatment option for previously untreated metastatic HER2+ gastric or GEJ adenocarcinoma
The triplet combination widens first-line treatment options based on overall response rate (ORR) and durability of response
Context: In May 2021, based on interim data from Phase III KEYNOTE-811, the FDA granted accelerated approval to the combination of Keytruda plus Herceptin and chemotherapy for previously untreated metastatic HER2+ gastric or GEJ cancer.
What’s new from ASCO: Merck presents for the first time data from the Phase III KEYNOTE-811 trial, which evaluates Keytruda in combination with Herceptin plus chemotherapy as first-line treatment for metastatic HER2+ gastric or GEJ cancer. Results from this trial demonstrate a meaningful improvement in ORR compared with standard of care Herceptin plus chemotherapy (74% vs. 52%, respectively; P = 0.00006) with comparable median duration of response (10.6 months vs. 9.5 months) and a safety profile consistent with that of immune checkpoint inhibitor therapy. Accelerated approval of this combination by the FDA was based on tumor response and durability of response.
What to expect: This novel combination is likely to provide substantial benefit for metastatic HER2+ gastric or GEJ cancer patients in this indication given their limited options and poor prognosis. Nevertheless, some oncologists may likely await PFS and OS results (coprimary endpoints) before adopting this combination more widely in clinical practice.
7. First phase III data for LAG-3 (relatlimab) and PD-1 (Opdivo) combination and new treatment option for malignant melanoma
Bristol Myers Squibb’s Relatlimab/Opdivo is poised to make inroads into its PD-1/CTLA-4 combination (Opdivo/Yervoy) share for malignant melanoma
Context: In March 2021, Bristol Myers-Squibb announced that RELATIVITY-047 met its primary endpoint of PFS compared with Opdivo alone, representing the first positive Phase III trial of a LAG-3 and PD-1 combination therapy in oncology.
What’s new from ASCO: Bristol Myers-Squibb disclosed the first presentation of results the Phase II/III RELATIVITY-047 trial (more detail in abstracts here and here), which compares relatlimab (LAG-3) and Opdivo (PD-1) with Opdivo alone in previously untreated unresectable or metastatic malignant melanoma. The combination shows a 5-month improvement in median PFS compared to Opdivo alone (10.1 vs. 4.6 months, respectively).
What to expect: Although gold standard overall survival (OS) data is yet to be reported for Bristol Myers-Squibb’s novel fixed dose LAG-3/PD-1 combination, it appears to show similar efficacy to its already established CTLA-4/PD-1 combination (even though there are no head-to-head data to truly compare). It also represents a safer and considerably more tolerable alternative. With a superior side effect profile, we anticipate there will be some shift away from CTLA-4/PD-1.
8. Armed with impressive ORR Data, can ciltacabtagene autoleucel become standard of care for heavily pretreated multiple myeloma?
Ciltacabtagene autoleucel sets the efficacy bar high for BCMA-targeting therapies for heavily pretreated multiple myeloma patients
Context: The recently approved B-cell maturation antigen (BCMA)-targeting agents Abecma (the first CAR T-cell therapy to secure FDA approval for multiple myeloma) and Blenrep (antibody-drug conjugate) address treatment of patients who have undergone at least four prior lines of therapy. In December 2020 and April 2021, Janssen submitted a rolling biological license application (BLA) to the FDA and a marketing authorization application (MAA) to the EMA, respectively, for its BCMA-targeting CAR T-cell therapy ciltacabtagene autoleucel based on the Phase Ib/II CARTITUDE-1 clinical trial, where the agent showed an overall response rate (ORR) of 97% in heavily pretreated multiple myeloma.
What’s new from ASCO: Ciltacabtagene autoleucel data from the multi-cohort Phase II CARTITUDE-2 study are equally impressive; the agent demonstrated an ORR of 95% [including 75% stringent complete remission (sCR) or complete remission (CR) in relapsed/refractory patients after one to three prior lines of therapy. While the median follow-up is short (5.8 months at data cutoff), the early and deep responses observed in this Phase II study are highly promising and bode well for ciltacabtagene autoleucel should it enter the market.
What to expect: With updated Phase I data for the bispecific BCMA and CD3-targeting antibody teclistamab (also from Janssen) also shared at ASCO, the landscape for BCMA-targeting therapies in multiple myeloma is becoming increasingly dynamic.
9. Calquence versus Imbruvica? Head-to-head data fuels future competition for BTK inhibitors
Will Calquence’s safety profile be enough to differentiate from standard of care Imbruvica in chronic lymphocytic leukemia (CLL)?
Context: Janssen/AbbVie’s Imbruvica and AstraZeneca’s Calquence are oral BTK inhibitors under evaluation in the pivotal Phase III ELEVATE-RR study; Calquence was the second BTK inhibitor to obtain regulatory approval for CLL and enters a competitive market dominated by current standard of care Imbruvica.
What’s new from ASCO: Data was shared from the first head-to-head study investigating Calquence versus Imbruvica in high-risk relapsed or refractory CLL. AstraZeneca’s noninferiority trial demonstrates comparable efficacy, with key safety and tolerability differences that will likely help to drive the use of Calquence in later treatment lines. ELEVATE-RR revealed that Calquence is noninferior to Imbruvica with a median PFS of 38.4 months in both arms (median OS not reached). Notably, Calquence was statistically superior to Imbruvica in all-grade atrial fibrillation (secondary endpoint), exhibited less frequent bleeding events, and resulted in fewer treatment discontinuations. However, headache and cough were more common with the novel BTK inhibitor.
What to expect: Cardiotoxicity and bleeding events have been a thorn in Imbruvica’s side to date, and these data bode well for Calquence’s future market uptake and use for relapsed or refractory patients. While physicians desire head-to-head data, unseating Imbruvica from its firmly entrenched position will remain a challenge.
10. VISION data for 177Lu-PSMA-617 offer new treatment option for heavily pretreated mCRPC patients
The biomarker-driven approach targets an underserved patient subpopulation, but how widely will the therapy be adopted in routine practice?
Context: In March 2021, Novartis announced that 177Lu-PSMA-617 met both its primary end points of OS and radiographic progression-free survival (rPFS) compared with standard of care in a heavily-pretreated patient population of high unmet need.
What’s new from ASCO: Novartis presents for the first time data for the PSMA-targeted radioligand therapy, 177Lu-PSMA-617, from the VISION study In patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with at least one taxane therapy and a second-generation hormonal therapy. Treatment with the radioligand achieved a statistically significant OS improvement (p<0.001) with a 38% reduction in the risk of death compared with standard of care.
What to expect: 77Lu-PSMA-617 presents a novel mechanism of action, and there is excitement for the PSMA-targeted therapy due to the high unmet need for alternative therapy options for this heavily pretreated patient subpopulation. Importantly, given the high level of PSMA expression in advanced prostate cancer, 77Lu-PSMA-617 targets a potentially large patient population. However, key considerations remain around treatment and referral pathways with radiopharmaceuticals; these are often quite complex, and historically, such therapies have only seen limited adoption in the real world.
There are exciting trends emerging from this years’ annual meeting, including the advance of targeted therapies to treat earlier stages of disease. For more in-depth analyses of key data emerging from the Annual Meeting, watch out for follow-up articles from our expert team.
Clarivate oncology experts who contributed to this article include Arman Esfandiari, Carolina do Pazo, Fiona Wiegert, Grace Mitchell, Laura Vinuesa, Liseth Parra, Priyanka Mehra, Snigdha Gupta, Sorcha Cassidy, Anamika Ghosh, Khurram Nawaz and Rachel Webster.
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References
- IMpower010: Primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC). ASCO 2021; Abstract 8500.
- OlympiA: A phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high risk HER2-negative early breast cancer. ASCO 2021; Abstract LBA1.
- Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: Randomized, double-blind, phase III KEYNOTE-564 study. ASCO 2021; Abstract LBA5.
- Adjuvant nivolumab (NIVO) in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): Expanded efficacy and safety analyses from CheckMate 577. ASCO 2021; Abstract 4003.
- Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study. Seeking approval, approved in ADC. ASCO 2021; Abstract LBA4001.
- Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: Initial findings of the global phase 3 KEYNOTE- 811 study. 1L accelerated. ASCO 2021; Abstract 4013.
- Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma. ASCO 2021; Abstract 9502
- Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: Primary phase III results from RELATIVITY-047 (CA224-047). ASCO 2021; Abstract 9503.
- CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy. ASCO 2021; Abstract 8013.
- Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM). ASCO 2021; Abstract 8007.
- First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia. ASCO 2021; Abstract 7500.
- Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). ASCO 2021; Abstract LBA4.
