ZOOMRX Global Oncology Panel’s Perspectives
The last couple of months have brought some high-profile developments in non-small cell lung cancer (NSCLC) including critical data released at the World Conference on Lung Cancer (WCLC‘24) as well as new regulatory approvals that can potentially change the landscape of PD-L1-positive and EGFRm advanced NSCLC treatment paradigms.
Following its dramatic press release in June, Summit Therapeutics released the much-anticipated HARMONi-2 data at the WCLC24 aiming to demonstrate the superior efficacy (PFS) of its bispecific ivonescimab over the current standard of care of Keytruda in the 1L PD-L1-positive advanced NSCLC.
The last month also brought several significant FDA approvals in EGFRm advanced NSCLC especially Rybrevant+Lazcluze in 1L and Rybrevant + chemotherapy in 2L, potentially challenging the well-established position of Tagrisso (and Tagrisso + chemotherapy) as the 1L standard of care in EGFRm mNSCLC.
ZoomRx conducted a survey with 100 oncologists in the US (N=50) and EU (N=50) Sept 16-19 to assess the immediate and longer-term impact of these latest developments.
Recent Lung Developments - Awareness & Excitement
Despite the big press release in June and HARMONi-2 recent data presentation at WCLC24, many oncologists in the US and Europe are not aware of HARMONi-2 trial.
The pivotal MARIPOSA trial that led to the approval of Rybrevant+Lazcluze topped the list of trials oncologists are aware of, along with the Dato-DXd TROPION Lung02 trial as well as Nivolumab perioperative vs. adjuvant trial in NSCLC, with large majorities of oncologists in the US and Europe being aware of these trials. By comparison, fewer oncologists - about 40% - were aware of HARMONi-2 data.
However, when it comes to the impact these trials may have, MARIPOSA and HARMONi-2 receive the highest levels of excitement among those oncologists aware of these developments. Given the recent approval of Rybrevant + Lazcluze in the US, the excitement about the MARIPOSA study is not surprising. The excitement about invonescimab data highlights oncologists’ reaction to the meaningful improvement in PFS that the trial demonstrated, with consistent efficacy results across patient subgroups.
Other trials that also captured the attention of oncologists include novel antibody drug conjugates (ADCs) – Datopotamab Deruxtecan and Ifinatamab Deruxtecan as well as the combination of novel agents with Imfinzi, reflecting the strong interest in ADCs as one of the most promising emerging classes of treatments in NSCLC and other solid tumors.
Perspectives on HARMONi-2
If approved, ivonescimab has the potential to challenge Keytruda as the 1L standard of care for patients with PD-L1-positive advanced NSCLC, however, oncologists express some reservations before they are ready to fully commit.
About half of oncologists in the US and Europe say that they would use ivonescimab as their new preferred option for 1L PD-L1 positive patients (non-squamous and squamous) if it were approved; about a third would use the two options equally and another 15% said they would hold on to Keytruda as their preferred 1L choice.
Note: Data for PD-L1 positive advanced squamous advanced NSCLC patients was comparable.
Oncologists mentioned their long-standing experience and trust supported by a long track of clinical evidence with substantial follow-up data available as a main reason for continued use of Keytruda as a preferred option. Only a few oncologists mentioned the study limitations including the choice of Keytruda monotherapy as a control arm for patients with 1-49% PD-L1 expression (rather than a combination of Keytruda with a chemotherapy) or limited geographic (China only) coverage of the clinical trial.
When asked directly whether the regulatory body (FDA, EMA) should approve ivonescimab based on a single-country trial, the US and EU oncologists were split. Most (~60% of) US oncologists leaned against the approval based on a single country trial, whereas the EU oncologists were mostly (70%) in favor of the regulatory approval based on a single country trial.
It’s important to note that the ZoomRx study was conducted around the same time as the FDA issued its draft guidance on oncology clinical trials on September 16th that expressed its position on the need for trials to go beyond a single country and encouraged companies to pursue multiregional trials. While we did not capture whether our respondents were aware of the FDA’s guidance, based on the ZOOMRX data, the US oncologists are mostly aligned with the FDA sentiment that a global study would be needed to determine whether ivonescimab should be approved in the US.
Perspectives on MARIPOSA
Rybrevant + Lazcluze regimen has the potential to alter the 1L EGFR+ advanced NSCLC treatment landscape. However, Oncologists’ experience and comfort with Tagrisso could lead to slower adoption of the Rybrevant + Lazcluze as a preferred treatment option in the 1L setting.
Oncologists express strong excitement about the MARIPOSA trial findings, driven by the efficacy (PFS) benefits of the Rybrevant + Lazcluze combination. Two-thirds (63-70%) of oncologists (across US and EU) mentioned that the trial findings are compelling to position Rybrevant + Lazcluze combination as a treatment option for 1L EGFR+ NSCLC treatment.
However, when we asked Oncologists directly whether Rybrevant+Lazcluze would replace Tagrisso +/- chemotherapy as their preferred treatment for 1L EGFRm advanced NSCLC patients, the oncologists were split, with about half saying that they would hold on to the existing SOC. Oncologists’ experience and comfort, proven efficacy benefits and well-established safety and convenience of dosing with Tagrisso are the primary reasons they mention for not changing their approach.
One fourth of oncologists would adopt Rybrevant + Lazcluze as their preferred 1L treatment choice, with the remaining quarter willing to consider both regimens equally.
The findings indicate that the compelling results from MARIPOSA trial are not yet sufficient to displace Tagrisso as the preferred option in 1L. However, the odds may shift towards Rybrevant with the SubQ formulation approval expected in the near future. When asked directly about the impact of the potential SubQ approval on their use of the Rybrevant + Lazcluze combination in 1L EGFRm advanced NSCLC, European oncologists expressed a strong preference to consider SubQ formulation combination, once approved. Nearly half of the US oncologists chose Rybrevant (IV & SubQ) + Lazcluze combination, with about one-third expressing equal preference for all available options.
Conclusions
Given the high levels of trust and well-established benefits of the SOC incumbents in the PD-L1-positive and EGFRm NSCLC, the new and potential newcomers will need to prove themselves “beyond the reasonable doubt” to challenge the existing paradigms.
Oncologists are setting a high bar for efficacy and patient quality of life for the new treatments before they are ready to change their preferences. As more convenient dosing formulation for the new treatments become available, this may change oncologists’ openness to the challenger therapies. The US oncologists also expect global, representative clinical trials before they are ready to accept the new options for their patients.
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