On 8 March, the US Food and Drug Administration (FDA) granted the accelerated approval of Roche ’s programmed cell death protein 1 (PD-1) inhibitor Tecentriq (atezolizumab) in combination with Abraxane (protein-bound paclitaxel) for the treatment of locally advanced or metastatic triple-negative breast cancer (TNBC).

The Tecentriq combination is approved for patients whose tumours are PD-L1 positive (defined by PD-L1 stained tumour-infiltrating lymphocytes [TILs] of any intensity covering less than or equal to 1% of the tumour area) as determined by the companion diagnostic assay, the VENTANA PD-L1 (SP142). This announcement marks the first approval of an immuno-oncology drug in breast cancer and signifies the introduction of a new treatment strategy in a therapeutically elusive subset of breast cancer.

Triple-negative breast cancer treatment

The use of PD-1 inhibitors, which harness the power of the immune system to fight cancer, has provided remarkable clinical successes in multiple cancer subtypes. Notable examples include melanoma, non-small cell lung cancer and bladder cancer. The clinical efficacy has led to the inevitable commercial success of PD-1 inhibitors, and immuno-oncology drug makers are now jostling for larger shares of this lucrative multi-billion-dollar market.

The approval of Tecentriq in TNBC is the latest inroad for this class of inhibitors. The approval was based on data derived from the IMpassion130 trial comparing Tecentriq + Abraxane versus placebo + Abraxane.

The Tecentriq-treated population benefited from a clear and unprecedented improvement in overall survival (OS) in patients who exhibit PD-L1 positive TILs (25.0 months versus 15.5 months).

The emergence of Tecentriq as the first-in-class PD-1 inhibitor in breast cancer represents a win for Roche in a PD-1 inhibitor market dominated by Merck & Co’s Keytruda (pembrolizumab) and Bristol-Myers Squibb ’s (BMS) Opdivo (nivolumab). Tecentriq is poised to temporarily monopolize the TNBC market until Merck & Co. is expected to release its data from two Phase III trials this year.

The first, KEYNOTE-119, compares single-agent Keytruda versus chemotherapy (of physician’s choice), while the second, KEYNOTE-355, compares Keytruda + chemotherapy (of physician’s choice) versus placebo + chemotherapy.

Therefore, despite the first-in-class success for Tecentriq in TNBC, Merck & Co’s active testing of Keytruda in a single-agent setting and in combination with chemotherapy of physician’s choice may ultimately allow Keytruda to be used in broader patient populations.

Opportunities also exist in the neoadjuvant/adjuvant setting, hormone-receptor-positive, and HER-2-positive breast cancers. Both Roche and Merck are investigating the use of their respective PD-1 inhibitors in each of these settings.

Triple-negative breast cancer competition

Further opportunities exist through novel combinations of PD-1 inhibitors with the recently approved poly ADP ribose polymerase (PARP) inhibitors in breast cancer patients harbouring BRCA1 (breast cancer type 1 susceptibility protein) mutations.

Needless to say, competition will be fierce and each of the immuno-oncology players will strive to carve out a therapeutic niche within the breast cancer market.

As pharmaceutical companies navigate the breast cancer market it is evident that the active pipeline in TNBC suggests an imminent transformation in the treatment paradigm for this historically difficult-to-treat subset of patients.

Also see: New frontier in treatment of triple-negative breast cancer