Development of better therapies in EGFR mutated tumors

This work was done in collaboration with Professor Kumar Prabhash and Professor Vanita Noronha. EGFR mutated tumours are seen in India in 20-30% of patients. We did a phase 3 randomised study comparing oral once-daily gefitinib with pemetrexed carboplatin intravenous therapy. The oral drug was found to improve disease control with fewer side effects and thus is considered standard therapy. This work was published in 2017. We further refined this therapy and saw whether the addition of intravenous chemotherapy to oral gefitinib improves outcome over gefitinib alone. It did indeed improve outcomes. Today this regimen has entered textbooks and guidelines as standard therapy for this cancer. Both these papers were published in ESMO OPEN and Journal of clinical oncology respectively.

Key takeaway: Conceptualised and proved how oral tablet of geftinib was superior to prevalent IV first-choice treatment. Then went a step ahead to provide robust data on how the addition of IV chemotherapy to the oral tablet was even better; this is now accepted as a standard treatment guideline and has been published as such by international bodies.

Development of low dose gemcitabine

This work was done in collaboration with Professor Kumar Prabhash and Professor Vanita Noronha. Prolonged infusion of low-dose gemcitabine (PLDG) in combination with platinum has shown promising activity in terms of improved response rate and progression-free survival (PFS); especially in squamous non-small cell lung cancer (NSCLC). Hence, we conducted a phase 3 randomized non-inferiority study with the primary objective of comparing the overall survival (OS) between PLDG and standard dose of gemcitabine with platinum. This study suggests that PLDG is an alternative to the standard gemcitabine schedule in squamous NSCLC, and either of these can be selected subject to patient convenience. This regimen could bring down treatment cost by 1/4th. This got accepted in EclinicalMedicine Journal. This is a Lancet group of journals.

Key takeaway: Conceptualized and then proved an alternative treatment being equally effective to the prevailing standard treatment in a type of lung cancer while being 25% cheaper.

Development of erlotinib maintenance

We planned to compare pemetrexed maintenance with erlotinib maintenance in non-squamous non-Epidermal Growth Factor Receptor (EGFR) mutated non-small cell lung cancer (NSCLC). The null hypothesis for this study was that there would be no difference in quality of life (QOL) between pemetrexed and erlotinib maintenance. The idea was to replace intravenous therapy with an oral drug. This would decrease hospital visits and the cost of treatment. The study was an open-label, single-centre, parallel, phase 3 randomized study with 1:1 randomization between maintenance pemetrexed arm and erlotinib arm. Both treatments had similar QOL suggesting that oral therapy could replace intravenous therapy.

Key takeaway: Proved that an oral drug gave a similar quality of life as the currently used IV drug in maintenance of a lung cancer thus providing an alternative that would allow decreased hospital visits and cost associated with having to give a drug by the IV route.

Immunotherapy in NSCLC

I have helped in establishing the safety and efficacy of immunotherapy in lung cancer, esophageal cancer, head and neck and CNS tumors in India. One of the first and largest series was published in this setting by Dr Patil and his colleagues.

Targeted therapies in Lung cancer/Head and Neck cancer/CNS/GI/other cancers

ALK, ROS, RET, MET, BRAF, NTRK, FGFR3 and other mutations are treated with multiple targeted therapies like Crizotinib, ceritinib, Lorlatinib, Alectinib, Brigatinib, selpercatinib, pralsetinib, capamatinib, tepotinib , larotrectinib or entrectinib, Pemigatinib, Erdafitinib, Vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) etc. Dr Patil has one of the largest experience which is published in most of them and is well worsed with there use.